!"#$%&'()*+&#$,-.

/#0$
112$3456377$

8*+&)+19#.$(:$;(*0(&<9$=(&/*(9$,-./#0.

!"#$"%&'()#*+)*#&,'-%.'(/%)0&,1,'
Thiee classes: (1) <0+&#., (2) 1#1/+'#.$<&'$1*(/#+&., anu (S) ./#*(+'.
!!"#$%&'$($#

)*+,-#./0*/,-1#
! All ueiivatives of amino aciu tyiosine
! i.e. thyioiu hoimones anu the catecholamines: epinephiine, noiepinephiine (auienal
meuulla), anu uopamine (hypothalamus)
! Theie aie two auienal glanus, one on top of each kiuney, anu each glanu contains an innei
-.#&%-2'$&.*22-, which secietes amine hoimones
! The suiiounuing -.#&%-2'+"#)&3 secietes steioiu hoimones
! Auienal meuulla secietes 4 times moie epinephiine than noiepinephiine because it
expiesses high amounts of an enzyme phenyl-N-methyltiansfeiase (PNNT), which
catalyzes the step that conveits noiepinephiine to epinephiine

2-!3+4-#5,4#20/3-+,#./0*/,-1#
! Nost hoimones aie eithei peptiues oi pioteins; some aie small peptiues (i.e. S amino
acius), otheis aie small pioteins
1. Initially synthesizeu on the iibosomes of enuociine cells as laigei pioteins calleu
piepiohoimones, which aie then cleaveu to piohoimones (by pioteolytic enzymes in
the iough ER)
2. Piohoimones aie packageu into vesicles by uolgi appaiatus
S. These vesicles contain the active hoimones as well as othei peptiue chains (that may
oi may not act like hoimones)
4. In the case wheie the vesicle is ieleaseu by exocytosis, the cell may be secieting
multiple peptiue hoimones that uiffei in theii effects on taiget cells

63-0/+4#./0*/,-1#
! Ring-like stiuctuie
! Synthesizeu in the auienal coitex anu gonaus (ovaiies anu testes), as well as placenta
uuiing piegnancy
! vitamin B is a steioiu
! Synthesis: In both gonaus anu auienal coitex, the cells aie stimulateu by the binuing of a
pituitaiy glanu hoimone to its ieceptoi
! Receptois aie linkeu to u-pioteins, which activate auenylyl cyclase anu thus cANP
piouuction
! Subsequent activation of piotein kinase A iesults in phosphoiylation of numeious
cytosolic anu membiane pioteins, which facilitate the subsequent steps in the piocess
! All of steioiu hoimones aie ueiiveu fiom )"(9#./#*(9
! Nost cholesteiol enteis the cells in the foim of low-uensity lipopioteins (LBLs)
! Receptois on the cell suiface binu to ciiculating LBLs; LBLieceptoi is biought into the
cell by enuocytosis; cholesteiol is stoieu as non-membiane-bounu lipiu uioplets
! When cell is stimulateu, fiee cholesteiol is ieleaseu foim the uioplet by enzyme
)"(9#./#*(9$#./#*<.#
! Caiiiei pioteins tianspoit fiee cholesteiol to the mitochonuiia (wheie they uevelop into
steioiu hoimones)
! Cholesteiol must fiist pass thiough the outei membiane to the innei membiane of the
mitochonuiia; they uo so via enzyme )-/()"*(0#$8>7?
! Cytochiome P4Su mouifies cholesteiol into inteimeuiates, which must be fuithei
mouifieu in oiuei to foim hoimones
! The final piouuct uepenus on the cell type anu the amounts of the enzymes it expiesses
! i.e. cells in the ovaiy expiess laige amounts of the enzyme neeueu to conveit testosteione
to estiauiol, wheieas cells in testes lack this enzyme anu only piouuce testosteione
! 0nce foimeu, steioiu hoimones leave the cell to the ISF to the bloou ciiculation
! Bounu to albumin

./0*/,-1#/7#38-#)40-,59#:/03-;#
! Five majoi hoimones secieteu: <9'(./#*(&#@$)(*/+.(9@$)(*/+)(./#*(&#@$
'#"-'*(#1+<&'*(./#*(&#$AB;%CD@$5,4$<&'*(./#&#'+(&&

42.",)&#"%&
! = Nineialocoiticoiu; has its effects on salt balance; mainly on the kiuneys' hanuling of
souium, potassium, anu hyuiogen ions
! (Piouuction of aluosteione is contiolleu by angiotensin II " acts on plasma membiane
ieceptois in auienal coitex to activate inositol tiisphosphate seconu messengei pathway
- uiffeient than cANP-meuiateu mechanism that piouuces steioius)

5"#)1,"2'anu Coiticosteione#
! = ulucocoiticoius; has effects on metabolism of glucose anu othei oiganic nutiients
! Coitisol is the pieuominant glucocoiticoiu in humans (coiticosteione is not as impoitant)
! Coitisol also facilitates the bouy's iesponses to stiess anu iegulation of immune system

6!74'anu anuiosteneuione
! = Anuiogens; incluues the male hoimone testosteione; all anuiogens have similai effects
as testosteione
! Auienal anuiogens aie less potent than testosteione fiom gonaus

()#*+)*#&'"8'4.#&%-2'+"#)&3'
! Composeu of thiee uistinct layeis
! 0utei layei: E(&<$F9(0#*G9(.< - mostly mineialocoiticoius (aluosteione)
! Niuule layei: E(&<$:<.)+)G9</< - mainly glucocoiticoius (coitisol)
! Insiue layei: E(&<$*#/+)G9<*+. - glucocoiticoius, piogestins anu anuiogens

./0*/,-1#/7#38-#</,541#
! Biffeient levels of key enzymes foi steioiu piouuction than in auienal coitex
! Contain high concentiations of enzymes in the anuiogen pathways leauing to
anuiosteneuione (like the auienal coitex)
! Bigh concentiation of enzyme that conveits anuiosteneuione to testosteione
! 0vaiian enuociine cells synthesize the female sex hoimones, which aie collectively
known as &,)#"9&%, (&,)#"%& anu &,)#-.1"2)
! Nales anu females house both testosteione anu estiauiol but in uiffeient quantities
! Enuociine cells of the coipus luteum, an ovaiian stiuctuie that aiises following ovulation,
secietes :#"9&,)&#"%&
! Note: cholesteiol " anuiosteneuione " testosteione " secieteu by testes
! Anuiosteneuione can be conveiteu to estione via. C*(0</<.#
! Likewise testosteione can be conveiteu to estiauiol via. Aiomatase

!"#$"%&';#-%,:"#)'1%')0&'<2"".
!!"#$($#
! Nost peptiue anu catecholamine hoimones aie watei soluble
! Tianspoiteu anu uissolveu by plasma
! Pooily soluble steioiu hoimones anu thyioiu hoimones ciiculate in the bloou laigely
bounu to plasma pioteins
! This means that theie aie "fiee hoimones" anu "bounu hoimones"
! Total hoimone concentiation iefeis to both of these
! 0nly fiee hoimones can uiffuse out of capillaiies anu encountei taiget cells

!"#$"%&'=&)->"21,$'-%.'73+#&)1"%
!!"#$(=#
! 0nce a hoimone has acteu on a taiget tissue, the concentiation of the hoimone in bloou
must be ietuineu to noimal
! Pievent excessive, haimful effects on cells
! Boimone's concentiation uepenus on two things:
1. Rate of secietion by enuociine glanu
2. Rate of iemoval fiom the bloou (livei anu kiuneys)
! Livei anu kiuneys aie not the only way to iemove hoimones
! Boimone can be metabolizeu by the cells upon which it acts i.e. peptiue hoimones:
enuocytosis of hoimone-ieceptoi complexes on plasma membianes enables cells to
iemove hoimones fiom suifaces anu catabolize them intiacellulaily
! Enzymes bieak uown catecholamines anu peptiue hoimones (takes a few minutes to an
houi)
! Bieak uown of steioiu hoimones anu thyioiu hoimones, because they aie piotein-bounu
anu piotecteu, take longei to be iemoveu fiom the system
! Bieak uown of a hoimone can activate it! i.e. testosteione " estiauiol oi
uihyuiotestosteione (which have uiffeient effects than testosteione on the cell)

=&+0-%1,$,'"8'!"#$"%&'4+)1"%
!!"$(='$(>#
./0*/,-#?-@-!3/01
! Because hoimones tiavel in the bloou, they aie accessible to all tissue cells
! Response to a hoimone is vERY specific
! Receptois foi peptiue hoimones anu catecholamines aie locateu on plasma membiane
! Receptois foi steioius anu thyioiu hoimones aie locateu insiue the cells
! 6"?%@#&9*2-)1"% = ueciease in ieceptoi numbei, tempoiaiy ueciease in iesponsiveness
! A:@#&9*2-)1"% = inciease in ieceptoi numbei, tempoiaiy inciease in iesponsiveness
! Boimones can up-iegulate anu uown-iegulate the ieceptois foi othei hoimones

A77-@31#/7#!-!3+4-#8/0*/,-1#5,4#@53-@8/95*+,-1
! Receptois locateu outsiue the cell
! This is impoitant because the hoimones aie too laige anu hyuiophilic to uiffuse thiough
the plasma membiane
! Activateu ieceptois uiiectly influence:
1. Enzyme activity that is pait of the ieceptoi
2. Activity of cytoplasmic janus kinases associateu with the ieceptoi
S. u pioteins coupleu in the plasma membiane to effectoi pioteins (ion channels anu
enzymes) that geneiate seconu messengeis such as cANP anu Ca
2+

! Peptiue hoimones anu catecholamines exeit both iapiu (non-genomic) anu uelayeu (gene
tiansciiption) actions on the same taiget cell

A77-@31#/7#13-0/+4#5,4#38B0/+4#8/0*/,-1
! Binuing of hoimone to ieceptois leaus to the activation (oi in some cases, inhibition) of
the tiansciiption of paiticulai genes, changes the iate of piotein synthesis encoueu by
those genes
! Suipiisingly, theie aie plasma membiane ieceptois foi ceitain steioiu hoimones i.e.
piogesteione anu estiauiol

2850*5@/9/C+@59#-77-@31#/7#8/0*/,-1
! Auministiation of laige quantities of hoimone foi meuical puiposes
! i.e. synthetic foim of coitisol = pieunisone, auministeieu to suppiess alleigic anu
inflammatoiy ieactions

B%:*),')0-)'+"%)#"2'!"#$"%&'(&+#&)1"%
!!"#$(D'$(&

! Nany hoimones aie secieteu in shoit buists, with little oi no ielease occuiiing between
buists
! Nay unueigo 24 houi cyclical vaiiations in theii secietoiy iates with uiffeient ciicauian
patteins foi uiffeient hoimones
! I.e. secietion of uB incieases uuiing the eaily peiiou of sleep anu uecieases uuiing the
iest of the night anu uay
! Causeu by cyclical vaiiations in activity of neuial pathways involveu in hoimone's ielease
! Boimone secietion contiolleu by:
1. Changes in plasma concentiations of mineial ions oi oiganic nutiients
2. Neuiotiansmitteis ieleaseu fiom neuions impinging on the enuociine cell
S. Anothei hoimone acting on enuociine cell
! Noie than one input may influence hoimone secietion
! 6-@0-3+/, = ielease of hoimone via exocytosis fiom cell
! Boimones like steioius may also uiffuse thiough the membiane

:/,30/9#EB#!951*5#@/,@-,3053+/,1#/7#*+,-059#+/,1#/0#/0C5,+@#,F30+-,31
! A majoi function of the hoimone is to iegulate, thiough negative feeuback, the plasma
concentiation of the ion oi nutiient contiolling its secietion
! I.e. insulin " plasma glucose concentiation
! i.e. Ca
2+
homeostasis " paiathyioiu hoimone; when plasma Ca concentiation uecieases,
PTB secietion is uiiectly stimulateu

:/,30/9#EB#,-F0/,1
! Auienal meuulla is a mouifieu sympathetic ganglion anu is thus stimulateu by
sympathetic pieganglionic fibeis
! i.e. insulin anu gastiointestinal hoimones aie stimulateu by neuions of the
paiasympathetic neivous system anu inhibiteu by sympathetic neuions
! Boimones secieteu by hypothalamus anu posteiioi pituitaiy aie unuei the uiiect contiol
of neuions in the biain (as opposeu to autonomic neivous system)

:/,30/9#EB#/38-0#8/0*/,-1
! In many cases the secietion of a paiticulai hoimone is uiiectly contiolleu by the bloou
concentiation of anothei hoimone
! Sometimes the only function of a hoimone in the bloou is to stimulate the secietion of
anothei = /*(1+)$"(*0(&#
! (When iefeiiing to giowth piomoting actions = 30/!8+@)
! Boimones also inhibit secietion of othei hoimones

;/:&,'"8'7%."+#1%&'61,"#.&#,
!!"#$(&'$(G#

1. Byposecietion
2. Bypeisecietion
S. Bypoiesponsiveness (of taiget cells)
4. Bypeiiesponsiveness (of taiget cells)

.B!/1-@0-3+/,
! Enuociine glanu is secieting too little hoimone, because it cannot function noimally =
1*+0<*-$"-1(.#)*#/+(&, examples:
1. Paitial uestiuction of a glanu (toxic chemicals anu infections)
2. An enzyme ueficiency iesulting in uecieaseu synthesis of the hoimone
S. Bietaiy ueficiency of iouine, leauing to uecieaseu secietion of thyioiu hoimone
! ,#)(&'<*-$"-1(.#)*#/+(& = enuociine glanu is not uamageu initially, but is ieceiving too
little of its tiopic hoimones
! 61-9%",1,C'To uiffeientiate between piimaiy anu seconuaiy conuitions " auministei
tiopic hoimone; if iesponsive, then seconuaiy hyposecietion may be uiagnoseu
! Note: this test sometimes uoesn't woik, because in the absence of tiopic hoimone foi
sufficient uuiation, the glanu atiophies
! ;#&-)$&%): auministei the missing hoimone oi a synthetic analog of the hoimone via
oial (pill), nasal (spiay), oi by injection

.B!-01-@0-3+/,
! D#1$-#/'0/:&#,&+#&)1"% = glanu is secieting too much of the hoimone on its own
! (&+"%.-#/'0/:&#,&+#&)1"% = excessive stimulation of the glanu by its tiopic hoimone
! =<G.#H$Nost common cause of 1e oi 2e is piesence of a hoimone secieting enuociine-cell
tumoi
! Tumois tenu to piouuce theii hoimones continually at a high iate even in the absence of
stimulation (they aie autonomous)
! 61-9%",1,C concentiations of the hoimone anu tiopic hoimone aie measuieu; if both aie
elevateu " hypeisecietion is seconuaiy; it is piimaiy " uecieaseu concentiation of
tiopic hoimone because of negative feeuback fiom the high concentiation of the
hypeisecieteu hoimone
! ;#&-)$&%): iemove tumoi, uiugs that inhibit hoimone's synthesis, oi uiugs that block
the hoimone's actions on its taiget cells

.B!/0-1!/,1+H-,-11#5,4#8B!-00-1!/,1+H-,-11
! An impoitant example of a uisease iesulting fiom 0/:"#&,:"%,1E&%&,, is '+<I#/#.$
0#99+/G. (type 2 uiabetes mellitus), in which the taiget cells of the hoimone insulin aie
hypoiesponsive to this hoimone
! 5-*,&: (1) ueficiency of oi abnoimal ieceptois foi the hoimone; i.e. inuiviuuals who aie
genetically "male" have a uefect that inuuces an absence of anuiogen ieceptois " cannot
piouuce male chaiacteiistics
! (2) Anothei cause: ieceptois aie noimal but an event occuiiing aftei the binuing of
hoimone to taiget cell may have occuiieu; i.e. activateu ieceptoi might be unable to
stimulate foimation of cyclic ANP
! (S) Boimones that iequiie metabolic activation by some othei tissue aftei secietion " a
ueficiency of the enzymes that catalyze the activation; i.e. men that seciete testosteione
lack the enzyme that conveits it to uehyuiotestosteione (effect on sex chaiacteiistics)
! !/:&##&,:"%,1E&%&,, can cause many pioblems. i.e. thyioiu hoimone causes up-
iegulation of ceitain ieceptois foi epinephiine; hypeisecietion of thyioiu hoimone
causes hypeiiesponsiveness to epinephiine " incieaseu heait iate (typical of people
with elevateu levels of thyioiu hoimones)

!"#$;-1(/"<9<0G.$<&'$8+/G+/<*-$J9<&'$
!!"#$$I'$$D#

5"%)#"2'(/,)&$,'1%E"2E1%9')0&'0/:")0-2-$*,'-%.':1)*1)-#/'

! 8+/G+/<*-$F9<&' = hypophysis lies at the base of the biain just below the hypothalamus
! It is connecteu to the hypothalamus by the +&:G&'+IG9G0 (a stalk containing neives anu
bloou vessels)
! Composeu of two lobes" <&/#*+(* (auenohypophysis) anu 1(./#*+(* (neuiohypophysis)
pituitaiies
! The anteiioi pituitaiy aiises embiyologically fiom an invagination of the phaiynx calleu
?538J-K1#!/F@8, wheieas the posteiioi pituitaiy is an extension of neuial components of
the hypothalamus
! (?-7-0#3/#7+CF0-#%%'%$L#!!"#$$I#7/0#5#4+5C05*#/7#38-#130F@3F0-1M
! The .G1*<(1/+) anu 1<*<K#&/*+)G9<* nuclei pass uown the infunuibulum anu enu within
the posteiioi pituitaiy in close pioximity to capillaiies (these neuions uo N0T synapse
with othei neuions) teiminals enu on capillaiies
! No impoitant connections bw hypothalamus anu anteiioi pituitaiy
! Capillaiies at the junction of the hypothalamus anu the infunuibulum foim the
"-1(/"<9<0(61+/G+/<*-$1(*/<9$K#..#9.
! The poital tiavels uown the infunuibulum stalk to the anteiioi pituitaiy wheie they uiain
into a seconu capillaiy beu
! Theiefoie the poital system offeis a uiiect ioute of bloou flow fiom hypothalamus to
anteiioi pituitaiy
! This offeis a iapiu iesponse anu minimizes the amount of the hypothalamic hoimone
neeueu to ieach an effective bloou concentiation (because the hoimone is not uiluteu into
the geneial ciiculation of the bouy)

2/13-0+/0#2+3F+350B#./0*/,-1
! Boimones aie piouuceu in the supiaoptic anu paiaventiiculai nuclei of the
hypothalamus
! Packageu as vesicles
! Stimuli such as neuiotiansmitteis geneiate action potentials in the neuions anu
piopagate the vesicles to axon teiminals (connecting a capillaiy beu) to tiiggei the
ielease of hoimones via exocytosis
! Boimone enteis bloou ciiculation
! LM-/()+&' stimulates contiaction of smooth muscle cells in the bieasts - milk ejection
uuiing lactation; stimulates contiaction of uteiine smooth muscles uuiing laboi
! Functions in males aie unknown
! N<.(1*#..+& - acts on smooth muscle cells aiounu bloou vessels to cause muscle
contiaction, which constiicts bloou vessels anu incieases bloou piessuie; acts within the
kiuneys to ueciease watei excietion in uiine, ietaining fluiu in the bouy- helps maintain
bloou volume
! vasopiessin = antiuiuietic hoimone (ABB)
! Biuiesis = loss of excess watei in uiine

),3-0+/0#2+3F+350B#8/0*/,-1#5,4#38-#8B!/38595*F1
! Bypothalamic hoimones (fiom the nuclei of the meuian eminence) contiol the secietion
of all the anteiioi pituitaiy hoimones
! ;-1(1"-.+(/*(1+)$"(*0(&#. = hypothalamic hoimones that iegulate anteiioi pituitaiy
function
! Theie aie othei hoimones (not secieteu by hypothalamus) that affect the anteiioi
pituitaiy
! Bopamine is the only hypothalamic hoimone that uoesn't affect the anteiioi pituitaiy
! Bypophysiotiopic hoimones aie the fiist in a 380--'hoimone sequence
1. Bypophysiotiopic hoimone contiols the secietion of.
2. An anteiioi pituitaiy hoimone, which contiols the secietion of.
S. A hoimone fiom some othei enuociine glanu
! Last hoimone acts on its taiget cells

NH-0H+-O#/7#5,3-0+/0#!+3F+350B#8/0*/,-1
! Secietes F hoimones
! 0nly G have well establisheu functions (these aie all peptiue hoimones):
HI Follicle stimulating hoimone (J(!) - gonaus to seciete sex hoimones (also iegulate
giowth anu uevelopment of ova anu speim)
KI Luteinizing hoimone (L!) - gonaus to seciete sex hoimones (also iegulate giowth
anu uevelopment of ova anu speim)
MI uiowth hoimone (N! oi somatotiopin) - livei to seciete OJP64 (insulin like giowth
factoi 1); also exeits uiiect effects on metabolism
OI Thyioiu-stimulating hoimone (;(! oi thyiotiopin) - thyioiu glanu to seciete
thyioxine anu tiiiouothyionine
PI Piolactin - it is unique in that its majoi function (unlike the othei S) is not to exeit
contiol ovei the secietion of a hoimone by anothei enuociine glanu, it stimulates the
uevelopment of the mammaiy glanus anu milk piouuction by uiiect effects upon the
bieasts; uuiing lactation, piolactin exeits a seconuaiy action to inhibit gonauotiopin
secietion, thus uecieasing feitility when a woman is bieast-feeuing. In male,
piolactin's iole is unceitain.
GI Auienocoiticotiopic hoimone (45;! oi coiticotiopin) - auienal coitex to seciete
coitisol
! Q(/#: LB anu FSB aie classifieu as gonauotiopins because they stimulate the gonaus
! The last foui aie secieteu by a uistinct cell type in the anteiioi pituitaiy
! The othei )?": beta-lipotiopin anu beta-enuoiphin have unknown physiological ioles
! In animal stuuies - beta-enuoiphin has pain-killing effects
! Beta-lipotiopin mobilizes fats in the ciiculation to pioviue extia fuel

.B!/!8B1+/30/!+@#8/0*/,-1
! Secietion of anteiioi pituitaiy hoimones is iegulateu by hypophysiotiopic hoimones
ieleaseu in the hypothalamus
! These hoimones aie secieteu by uisciete nuclei in hypothalamus anu teiminate in
meuian eminence aiounu the capillaiies of the hypothalamo-pituitaiy poital vessels
! Action potentials seciete them by exocytosis
! Boimones tiavel thiough the poital vessels to the anteiioi pituitaiy
! Theie they act on vaiious pituitaiy cells to contiol theii secietion

.B!/38595*+@#,-F0/,1#3/#38-#!/13-0+/0#H1"#5,3-0+/0#!+3F+350B#
! Axons of hypothalamic neuions that seciete the posteiioi pituitaiy hoimones leave the
hypothalamus anu enu in posteiioi, wheieas those that seciete hypophysiotiopic
hoimones iemain in hypothalamus enuing in meuian eminence
! The posteiioi pituitaiy capillaiies, wheie the posteiioi hoimones aie secieteu empty into
the main blooustieam, wheieas hypophysiotiopic hoimones entei capillaiies in meuian
eminence, which aie caiiieu thiough the poital vessels to the anteiioi pituitaiy
! The hypophysiotiopic hoimones leave the capillaiies of the anteiioi anu bathe the
pituitaiy cells, exeiting a uiiect effect on secietion of anteiioi cells
! If a pituitaiy cell iesponus (baseu on a specific ieceptoi) it will ielease the hoimone,
which will uiffuse into the capillaiies that secieteu the hypophysiotiopic hoimones, anu
entei the blooustieam

.B!/!8B1+/30/!+@#8/0*/,-1#@/,3+,F-4#
! Coiticotiopin-ieleasing hoimone (5Q!) " ACTB
! uiowth hoimone ieleasing hoimone (N!Q!) " uB
! Thyiotiopin-ieleasing hoimone (;Q!) " TSB (thyiotiopin oi thyioiu stimulating
hoimone)
! uonauotiopin-ieleasing hoimone (N%Q!) " LB anu FSB
! Q(/#: two hypophysiotiopic hoimones uo not 13+*F953- the ielease of an anteiioi
pituitaiy hoimone, but iathei +,8+E+3 its ielease:
! Somatostatin ((() "inhibits uB
! Bopamine (64) "inhibits piolactin
! uB is contiolleu by two hypophysiotiopic hoimones
! But how aie hypophysiotiopic hoimones contiolleu.

P-F059#@/,30/9#/7#8B!/!8B1+/30/!+@#8/0*/,-1
! A laige numbei of neuiotiansmitteis, paiticulaily the catecholamines anu seiotonin aie
ieleaseu at the synapses on these hoimone-secieting hypothalamic neuions
! Biugs that influence these neuiotiansmitteis also have an effect
! i.e. neuial inputs " inciease CRB secietion " inciease ACTB secietion " inciease
coitisol secietion " negative feeuback on CRB anu ACTB secietions
! Physical anu emotional stiess act via neuial pathways to contiol secietion

./0*/,59#7--4E5@J#@/,30/9#/7#38-#8B!/38595*F1#5,4#5,3-0+/0#!+3F+350B#
! In the example of ACTB-coitisol sequence,
! Coitisol acts upon the hypothalamus to ieuuce synthesis anu secietion of CRB
! Also acts on anteiioi pituitaiy to ieuuce iesponse of the ACTB secieting cells to CRB
! Negative loops help maintain ieasonable hoimone levels
! R(&F69((1$&#F</+K#$:##'I<)S - i.e. coitisol feeubacking on hypothalamus (thiiu
enuociine glanu hoimone in sequence acting on the fiist)
! Long loop feeuback uoes not exist foi piolactin because piolactin uoes not have a majoi
contiol ovei anothei enuociine glanu, it uoes not paiticipate in a thiee-hoimone
sequence
! Theie is still feeuback in the piolactin system
! i.e. piolactin acts on hypothalamus to 13+*F953- the secietion of uopamine, which then#
+,8+E+31 the secietion of piolactin
! The influence of the anteiioi pituitaiy hoimone on the hypothalamus is shoit-loop
feeuback i.e. uB anu piolactin

Q8-#0/9-#/7#R,/,1-SF-,@-T#8/0*/,-1#/,#38-#8B!/38595*F1#5,4#5,3-0+/0#!+3F+350B
! Nonsequence hoimones, that is hoimones that uo not paiticipate in the S-pait sequence
mentioneu befoie, still exeit impoitant influences on the secietion of hypophysiotiopic oi
anteiioi pituitaiy hoimones
! i.e. estiauiol enhances the secietion of piolactin by the anteiioi pituitaiy

!"#$!"-*(+'$J9<&'
!!"#$$&#'$=%

! Actions of TB aie vERY impoitant anu the consequences of its imbalance aie vERY seveie
! Thyioiu glanu piouuces two iouine-containing molecules: /"-*(M+&# (T4) - 4 iouines'anu
/*++('(/"-*(&+&# (TS) - S iouines
! T4 is geneially conveiteu into TS by enzymes '#+('+&<.# in taiget cells
! TS is the majoi thyioiu hoimone
! T4 is the majoi secietoiy piouuct of the thyioiu anu total T4 concentiations aie highei in
the bloou

6B,38-1+1#/7#Q8B0/+4#./0*/,-1#
! A bi-lobeu stiuctuie that sits within the neck stiauuling the tiachea
! Becomes functional eaily in life
! Weighs 2S g at auulthoou
! Within the thyioiu glanu aie numeious follicles, each composeu of an encloseu spheie of
highly specializeu cells suiiounuing a coie containing a piotein-iich mateiial calleu the
+"22"1.
! Folliculai cells paiticipate in all phases of thyioiu hoimone synthesis anu secietion
! Synthesis begins with ciiculating iouiue cotianspoiteu with Na ions acioss folliculai cell
plasma membiane
! 0nce insiue, the iouiue ions aie too bulky to leave - "iouiue tiapping"
! Souium is pumpeu out with NaK - ATPase pump
! Tiappeu negatively chaigeu iouiues uiffuse uown electiical anu concentiation giauients
to the luminal boiuei of the folliculai cells
! Colloiu of the follicles contains laige amounts of piotein calleu )0/#"92">*21%
! Iouiue is oxiuizeu at the luminal suiface of folliculai cells to iouiue fiee iauicals
! These attach to phenolic iings of tyiosine molecules within the amino aciu stiuctuie of
thyioglobulin
! (Thyioglobulin itself is synthesizeu by the folliculai cells anu secieteu by exocytosis into
the follicle lumen)
! Iouiues aie oxiuizeu by )0/#"1. :&#"31.-,&
! Theie aie two positions on a given tyiosine: one iouine attacheu is calleu
0(&(+('(/-*(.+&#$ATO!D anu two iouines attacheu is calleu '++('(/*-(.+&#$ABO!D
! The next mechanisms is uncleai: phenolic iing of a molecule of NIT oi BIT is iemoveu
fiom the iemainuei of its tyiosine anu coupleu to anothei BIT on the thyioglobulin
molecule (possibly meuiateu by thyioiu peioxiuase)
! Two BIT molecules = T4
! 1 BIT + 1NIT = TS
! These hoimones aie secieteu by the following mechanism: extensions of the colloiu-
facing membianes of folliculai cells engulf poitions of the colloiu (with iouinateu
thyioglobulin) by enuocytosis
! The thyioglobulin, with its coupleu NITs anu BITs is biought into contact with lysosomes
in the cell inteiioi
! Pioteolysis of thyioglobulin ieleases TS anu T4, which then uiffuse out of the folliculai cell
into the inteistitial fluiu anu fiom theie to the bloou

:/,30/9#/7#Q8B0/+4#UF,@3+/,#
! All of the actions of folliculai cells aie stimulateu by TSB which is stimulateu by TRB
! Basic contiol mechanism of TSB piouuction is the negative feeuback action of TB on the
anteiioi pituitaiy anu (to a lessei extent) the hypothalamus
! TSB = tiophic hoimone - stimulates TS anu T4 piouuction as well as incieasing piotein
synthesis in folliculai cells, incieasing BNA ieplication anu cell uivision anu the amounts
of iough ER neeueu foi piotein synthesis
! Thus if thyioiu cell is exposeu to highei TSB levels than noimal it will hypeitiophy
(inciease in size) = 9"1)&#

C)/+(&.$(:$!"-*(+'$"(*0(&#.'
! TB ieceptois aie uistiibuteu thioughout the bouy, unlike othei hoimones wheie it is
limiteu
! Actions of TS anu T4 aie wiuespieau anu affect many oigans anu tissues
! Nost binuing sites aie ieseiveu foi TS because T4 is ueiouinateu
! TS anu T4 act by inuucing gene tiansciiption anu piotein synthesis
V-35E/9+@#5@3+/,1
! Effects on caib anu lipiu metabolism (not to the extent of insulin)
! TB stimulates caib absoiption fiom the small intestine anu incieases fatty aciu ielease
fiom auipocytes
! Pioviue eneigy to maintain metabolic iate at a high level
! Stimulates the activity of NaK - ATPases thioughout the bouy
! Q(/#: ATP negatively feeus back on glycolytic enzymes within cells to maintain its cellulai
concentiation
! A ueciease in cellulai stoies of ATP tiiggeis an inciease in glycolysis which iesults in the
buining of auuitional fuel to iestoie ATP levels
! By-piouuct: heat
! ATP is consumeu by NaK-ATPase at a high iate uue to TB activation

2-0*+11+H-#)@3+/,1
! TB affects catecholamines
! TB up-iegulates beta-auieneigic ieceptois in many tissues notably the heait anu neivous
system
! Excess thyioiu hoimone concentiation closely iesembles some of the symptoms of excess
epinephiine anu noiepinephiine
! This is because the incieaseu thyioiu hoimone potentiates the actions of catecholamines
! Because of this potentiating effect, people with hypeithyioiuism aie often tieateu with
uiugs that block beta-auieneigic ieceptois to alleviate the anxiety, neivousness, anu
"iacing heait" associateu with excessive sympathetic activity

<0/O38#5,4#4-H-9/!*-,3
! TB is an impoitant hoimone foi giowth i.e. absence of TB stunts giowth in chiluien
! Buiing fetal life, TB stimulates the giowth of the cential neivous system i.e. uenuiites,
synapses, anu uenuiitic extensions
! i.e. absence of TB uuiing fetal uevelopment iesults in mental ietaiuation - +#&)1%1,$
! Common cause of cietinism is uietaiy iouine ueficiency in mothei, cannot manufactuie
TB foi fetus
! Can be pieventeu if coiiecteu with iouine anu TB auministeieu shoitly aftei biith
! Eviuence suggests that complete noimal mental function may not be iestoieu
! If tieatment is not initiateu in the eaily neonatal peiiou, cietinism cannot be ieveiseu
! Cietinism is moie common in mountainous iegions wheie snow anu iainwatei leach
iouine out of the soil
! TB is not limiteu to neonatal uevelopment
! TB is also neeueu foi piopei neive muscle ieflexes anu foi noimal cognition in auults
! Thyioiu uiseases aie the most common of all enuociine uiseases

;-1(/"-*(+'+.0$K.2$;-1#*/"-*(+'+.0$

.B!/38B0/+4+1*#
! TB plasma levels aie below noimal = 0/:")0/#"1.1,$
! Nost +-*,&, - 9S % - aie piimaiy uefects iesulting fiom uamage to oi loss of functional
thyioiu tissue oi inauequate iouine consumption
! Iouine ueficiency = ueciease in TB
! This piouuces a negative feeuback on the hypothalamus anu pituitaiy anu TRB become
chionically elevateu in the poital ciiculation of the anteiioi pituitaiy
! Plasma TSB concentiation is thus elevateu (iemembei TSB's effects on the thyioiu glanu
" stimulates the tiansciiption of pioteins anu oiganelles, causes inciease in glanu size)
! Results = goiteis which can ieach astounuing sizes if untieateu
! ;#&-)$&%) of goitei: incluue iouine in uiet
! veiy iaie in the 0niteu States uue to iouizeu salt
! Nost common cause of hypothyioiuism in 0.S. is autoimmune uestiuction of the thyioiu
glanu (<G/(+00G&#$/"-*(+'+/+.) i.e. ;<."+0(/(U.$'+.#<.# - T cells of immune system
attack anu uestioy thyioiu tissue
! Like many othei autoimmune uiseases, Bashimoto's uisease is moie pievalent in women,
slowly piogiessing with age
! ;#&-)$&%) of Bashimoto's - uaily ieplacement with phaimaceutical piepaiations of T4
(iestoies the thyioiu hoimone levels in the bloou anu causes the TSB levels to ueciease to
noimal)
! (/$:)"$, of hypothyioiuism - colu intoleiance anu tenuency towaiu weight gain
! Both of these symptoms aie causeu by uecieaseu caloiigenic actions piouuceu by thyioiu
hoimone
! 0thei nonspecific symptoms: fatigue, changes in skin tone, haii, appetite, gastiointestinal
function, anu mental function
! Recall that TB potentiates the actions of epinephiine anu noiepinephiine
! TB also pievents the ovei-expiession of a hyuiophilic compounu - 92/+",-$1%"92/+-%,
that aie founu in inteistitial spaces in scatteieu iegions of the bouy
! If hypothyioiuism is left untieateu, watei accumulates anu gets tiappeu within these
compounus anu causes chaiacteiistic puffiness of the face anu othei iegions - 0-M#'#0<

.B!-038B0/+4+1*#
! Theie aie also veiy iaie cases of hoimone-secieting tumois of the thyioiu
! The most common foim is J*<K#U.$'+.#<.#
! Like Bashimoto's, uiave's is moie common in women anu may have a giauual onset
! The plasma of patients with uiaves' contains antibouies that iecognize the TSB ieceptoi
on the thyioiu glanu
! The glanu is stimulateu by the antibouies
! This iesults in "-1#*/*(1"- of the glanu anu incieaseu TB piouuction
! Q(/#: that goitei can be causeu by both hypei anu hypothyioiuism
! TS anu T4 feeu back on the hypothalamus anu pituitaiy glanu
! Thus uiaves' uisease is chaiacteiizeu by elevateu TB levels uespite suppiesseu TSB
! Constant stimulation of the glanu causes it to hypeitiophy anu iesults in goitei
! (/$:)"$, of hypeithyioiuism: heat intoleiance, weight loss, anu often show signs of
incieaseu sympathetic neivous system activity (anxiety, tiemois, jumpiness, incieaseu
heait iate)
! This is veiy seiious to the caiuiovasculai system uue to its peimissive actions on
catecholamines
! ;#&-)$&%): uiugs that inhibit thyioiu hoimone synthesis, suigical iemoval of the glanu,
oi by uestioying a poition of the thyioiu using iauioactive iouine
! Aftei tieatment, patients have to consistently ingest pills to maintain TS anu T4 levels



because it is a trophic
hormone
!"#$%&'()*+&#$V#.1(&.#$/($,/*#..

! Basic enuociine iesponses to stiess is the sense of ieal oi potential thieats to
homeostasis i.e. infection, shock, pain, fiight, sleep uepiivation
! Response to all of these iesults in the ielease of )(*/+.(9
1. Bouy iesponus to stiess by a neuial input to the hypothalamus, which inuuces
secietion of CRB
2. CRB acts on the anteiioi pituitaiy to ielease ACTB
S. ACTB acts on the auienal coitex to ielease coitisol
! The ielease of ACTB anu coitisol is contiolleu by seveial hoimones i.e. K<.(1*#..+&,
which usually incieases the iesponse to stiess
! Cytokines (secietions of cells in immune system) stimulate ACTB secietion

28B1+/9/C+@59#7F,@3+/,1#/7#@/03+1/9#
! Coitisol also has non-stiess actions
! i.e. peimissive actions to epinephiine anu noiepinephiine of muscle cells that suiiounu
bloou vessels
! Thus basal levels of coitisol aie neeueu to maintain noimal bloou piessuie
! Basal levels aie iequiieu to maintain the cellulai concentiations of ceitain enzymes in
metabolic homeostasis
! Anti-inflammatoiy anu inflammatoiy functions
! Inhibits piouuction of both leukotiienes anu piostaglanuins, both of which aie involveu
in inflammation
! Reuuces capillaiy peimeability in injuieu aieas, to ieuuce fluiu leakage to inteistitium
! In uiseases in which coitisol is gieatly ieuuceu, an incieaseu inciuence of autoimmune
uisease is sometimes noticeu
! Coitisol is also an impoitant hoimone uuiing fetal anu neonatal life
! Implicateu in the piopei uiffeientiation of numeious tissues anu glanus incluuing vaiious
paits of the biain, the auienal meuulla, the intestine anu notably, the 2*%9,
! Coitisol thus has an impoitant iole in non-stiess situations

UF,@3+/,1#/7#:/03+1/9#+,#630-11
! Piimaiy effects is on the oiganic metabolism to mobilize fuels: inciease the plasma
concentiations of glucose, fatty acius, glyceiol, amino acius
! (Catabolizes piotein anu fat to pioviue eneigy anu inhibits giowth anu iepiouuction)
! Coitisol-inuuceu effects on oiganic metabolism aie as follows:
1. Any patient subjecteu to suigeiy catabolizes consiueiable quantities of bouy piotein
2. A uiabetic who suffeis an infection iequiies moie insulin than usual
S. A chilu subjecteu to seveie stiess of any kinu may manifest ietaiueu giowth
! It incieases ability of vasculai smooth muscle to contiact in iesponse to noiepinephiine
! I.e. a patient lacking coitisol faceu with moueiate stiess, which usually ieleases unknown
vasouilatois, may uevelop hypotension (causeu by vasouilatois)
! A peison exposeu to seveie stiess can uie, usually of ciiculatoiy failuie if his plasma
concentiation is too low
! Auministiation of laige quantities of coitisol piofounuly ieuuces inflammatoiy iesponse
to injuiy oi infection, i.e. a valuable tieatment to alleigy anu aithiitis
! Incieaseu plasma coitisol typical of infection oi tiauma exeits a uampening effect on the
bouy's immune iesponses, piotecting against possible uamage fiom excessive
inflammation

N38-0#8/0*/,-1#0-9-51-4#4F0+,C#130-11#
! C9'(./#*(&#@$K<.(1*#..+&$ACB;D@$F*(W/"$"(*0(&#@$F9G)<F(&@$<&'$I#/<6#&'(*1"+&
(which is coieleaseu fiom the anteiioi pituitaiy with ACTB)
! Insulin secietion uecieases
! vasopiessin anu aluosteione act to ietain watei anu souium in the bouy (an impoitant
featuie in the face of potential loss of watei oi hemoiihage)
! vasopiessin stimulates secietion of ACTB
! The oveiall effects of these hoimones is the same as coitisol anu epinephiine " to
mobilize eneigy stoies
! Beta-enuoiphin in stiess may be ielateu to pain-killing effects
! Sympathetic neivous system plays a iole in :+F"/6(*6:9+F"/ iesponse - incieaseu
epinephiine fiom auienal meuulla

21B@8/9/C+@59#130-11#5,4#4+1-51-
! It is possible that incieaseu coitisol can ueciease the activity of the immune system
enough to ieuuce the bouy's iesistance to infection
! It can also woisen the symptoms of uiabetes because of its effects on bloou glucose, cause
an inciease in ueath iate of ceitain neuions
! As a iesult of incieaseu bloou lipiu concentiation it may cause atheioscleiosis anu
hypeitension

C'*#&<9$+&.G::+)+#&)-$<&'$=G."+&FU.$.-&'*(0#$

! C'*#&<9$+&.G::+)+#&)- = coitisol levels aie veiy low
! (/$:)"$,: lethaigy anu loss of appetite
! Examination may ieveal low bloou piessuie (coitisol is neeueu foi caiuiovasculai actions
of epinephiine) anu low bloou sugai (loss of noimal metabolic actions of coitisol)

20+*50B#540-,59#+,1F77+@+-,@B
! Loss of auienal coitical function, i.e. infectious uiseases like /GI#*)G9(.+. infiltiates the
auienal glanus anu uestioys them
! 5-*,&: uue to an autoimmune attack, wheie the immune system mistakenly iecognizes
some component of a peison's own auienal cells as foieign
! All of the zones of the auienal coitex aie affecteu
! So coitisol -%. aluosteione levels aie uecieaseu below noimal
! Beciease in aluosteione causes imbalance in souium, potassium, anu watei in bloou
! Loss of salt anu watei balance leaus to hypotension
! Piimaiy auienal insufficiency fiom any of the above causes is also known as C''+.(&U.$
'+.#<.#
! Piogiesses slowly
! It is noimally misuiagnoseu as )"*(&+)$:</+FG#$.-&'*(0# because some patients with
piimaiy auienal insufficiency may exhibit anxiety oi emotional pioblems
! ACTB levels aie gieatly incieaseu uue to the loss of negative feeuback actions of coitisol
! ;#&-)$&%): uaily oial auministiation of glucocoiticoius anu mineialocoiticoius


6-@/,450B#540-,59#+,1F77+@+-,@B
! Nay aiise fiom pituitaiy uisease
! Symptoms aie less uiamatic than piimaiy auienal insufficiency because aluosteione
secietion (uoesn't iely on ACTB) is maintaineu by othei mechanisms
! It isn't noimally as seveie as piimaiy auienal insufficiency
! Excess glucocoiticoius
! =G."+&FU.$.-&'*(0# = excess coitisol in bloou even in non-stiesseu inuiviuual
! 5-*,&:
1. 8*+0<*-$'#:#)/: coitisol-secieting tumoi of the auienal
2. ,#)(&'<*-$'#:#)/: uue to an ACTB secieting tumoi of the pituitaiy glanu (=G."+&FU.$
'+.#<.#D, which accounts foi most cases of Cushing's synuiome
! Incieaseu bloou levels of coitisol tenu to piomote uncontiolleu catabolism of bone,
muscle, skin, anu othei oigans ((./#(1(*(.+.)
! Peison with Cushing's may show same symptoms as those with uiabetes
! O00G&(.G1*#..+(& = anti-immune actions of coitisol
! (/$:)"$,: incieaseu appetite, obesity, hypeitension (potentiate effects of epinephiine
anu noiepinephiine); at high enough levels, coitisol exeits aluosteione-like actions on the
kiuney
! ;#&-)$&%): uepenus on the cause
! Cushing's uisease: suigical iemoval of pituitaiy tumoi
! 0nilateial auienalectomy foi an auienal tumoi making too much coitisol
! Q(/#: glucocoiticoius aie often useu theiapeutically to tieat inflammation, lung uisease,
anu othei uisoiueis, if too much is auministeieu, the siue effect can be Cushing's
synuiome.

%&'()*+&#$=(&/*(9$(:$J*(W/"

! The enuociine system contiols giowth
! uiowth is ueteimineu specifically by bone giowth, paiticulaily in veitebial column anu
legs

W/,-#<0/O38
! Bone is composeu of a piotein matiix calleu )(99<F#&,
! Beie calcium salts, i.e. calcium phosphates aie uepositeu
! The bone is uiviueu into two paits: #1+1"-.#. anu ."<:/.
! Each epiphysis in contact with the shaft is contains a caitilage #1+1"-.#<9$F*(W/"$19</#
! L./#(I9<./. aie the bone-foiming cells that conveit the caitilaginous tissue at the euge to
bone, while )"(&'*()-/#. lay new caitilage uown in the inteiioi of the plate
! Lineai giowth continues as long as the caitilage plate is piesent, if it has tuineu to bone,
giowth stops. This is known as #1+1"-.#<9$)9(.G*# anu occuis at uiffeient times in
uiffeient bones, theiefoie a peison's bone age can be ueteimineu by x-iaying anu
ueteimining which have gone thiough epiphyseal closuie
! Two iapiu giowth phases: one at 2 yeais anu one at pubeity
! Boys begin pubeity 2 yeais latei than giils


A,H+0/,*-,359#75@3/01#+,79F-,@+,C#C0/O38
! Bealthy giowth is uepenuent on sufficient nutiients anu fieeuom fiom uisease
! Nalnutiition causes giowth ietaiuation in fetus
! Iiieveisible stunting of biain uevelopment is causeu by pienatal malnutiition
! Thus piopei nutiition in the pienatal anu natal stages of life is essential
! Inteiestingly a tempoiaiy peiiou of stunteu giowth (excluuing giain uevelopment) can be
ieveiseu (anu expeiience a iemaikable giowth spuit) once the chilu ietuins to a piopei
uiet

;(*0(&<9$+&:9G#&)#.$(&$F*(W/"$

! Nost impoitant giowth hoimones: +&.G9+&69+S#$F*(W/"$:<)/(*.$O anu OO@$/"-*(+'$
"(*0(&#@$+&.G9+&@$/#./(./#*(&#@$anu #./*(F#&.
! J*(W/"$:<)/(*. - peptiue hoimones act as paiaciine anu autociine agents to stimulate
cell uivision - these aie calleu mitogens (something that stimulates cell uivision)
! J*(W/"$+&"+I+/+&F$:<)/(*. inhibit cell uivision in specific tissues

<0/O38#8/0*/,-#5,4#+,1F9+,'9+J-#C0/O38#75@3/01
! uB has no effect on fetus, but plays a huge iole in postnatal giowth
! Najoi function is stimulation of cell uivision in many taiget tissues
! i.e. piomotes bone lengthening by stimulating matuiation anu cell uivision of
chonuiocytes in epiphyseal plates, continuously wiuening plates anu pioviuing moie
caitilaginous mateiial
! Bowevei it uoesn't have uiiect effects on cells
! It uoes it inuiiectly thiough the mitogen'insulin-like giowth factoi I (OJP64)
! 0nuei influence of uB, it is secieteu by livei, enteis the bloou anu functions as a hoimone
! IuF-1 acts as paiaciineautociine agent
! Nechanism:
1. uB stimulates chonuiocyte piecuisois (foi example) to uiffeientiate into
chonuiocytes. (uB stimulates all cell piecuisois)
2. Buiing uiffeientiation chonuiocytes seciete IuF-1 as well as become iesponsive to
IuF-1
S. IuF-1 acts as paiaciineautociine agent to stimulate the uiffeientiating chonuiocytes
to unueigo cell uivision
! BW<*:+.0 - uecieaseu uB secietion anu uecieaseu IuF-1 piouuction oi failuie of tissues
to iesponu to IuF-1
! R<*(&$BW<*:+.0 (giowth hoimone insensitivity synuiome) is causeu by a genetic
mutation that causes the giowth hoimone ieceptoi to fail to iesponu to giowth hoimone
! Secietion of IuF isn't limiteu to uB, it is also affecteu by nutiition
! uB uiiectly stimulates piotein synthesis in vaiious tissues anu oigans i.e. muscle
! It uoes so by incieasing aa uptake anu both the synthesis anu activity of iibosomes "
causes muscles anu oigans to enlaige
! Remembei that uB secietion is stimulateu by uBRB anu inhibiteu by somatostatin
! These ieleasing hoimones aie 18u out of phase with each othei, i.e. this means that when
one is up, the othei is uown
! They aie ieleaseu in episouic buists
! Buiing the uay little oi no uB is secieteu
! Right aftei someone falls asleep i.e. 1-2 houis aftei, piolongeu buists of secietion may
occui
! A vaiiety of othei hoimones also affect uB secietion i.e. sex, thyioiu, insulin
! Net iesult of all these inputs = uB is at the highest uuiing auolescence (anu lowest in
auults)
! Becieaseu in uB with aging is causeu by loss of lean bouy anu bone mass anu expansion
of auipose tissue
! uB has been synthesizeu with BNA iecombinant technology to help shoit-statuie
chiluien to giow, B0WEvER it is also abuseu by athletes
! uB auministiation to a healthy inuiviuual has seiious siue-effects i.e. symptoms similai to
uiabetes mellitus
! Elevateu uB cause a uisease calleu - <)*(0#F<9-
! Although uB has no effect on the fetus, IuF-1 plays a majoi iole on fetal uevelopment,
especially foi the giowth of the fetal neivous system
! OJP6X plays an impoitant iole in pienatal uevelopment, its postnatal iole is unknown

Q8B0/+4#./0*/,-1
! Absolutely neeueu foi noimal giowth
! Najoi iole: Requiie foi the synthesis anu giowth piomoting effects of uB
! i.e. infants with hypothyioiuism have ietaiueu giowth, uue to sloweu bone giowth

X,1F9+,
! Besiues its ability to piomote entiy of glucose anu aa into the cell.
! Najoi iole: It stimulates stoiage of fat anu inhibits piotein uegiauation
! Bas a uiiect effect on cell uiffeientiation anu uivision uuiing fetal life

6-;#8/0*/,-1
! uiowth spuit at 8-1u iequiies sex hoimones
! Najoi iole: stimulate secietion of uB anu IuF-1
! It also stops bone giowth by inuucing epiphyseal closuie
! It thus has a uual effect
! Testosteione (but not estiogen) exeits a uiiect anabolic effect on piotein synthesis in
noniepiouuctive tissues i.e. muscle
! Explains why men have moie mass than women
! Also abuseu by no-goou cheateis
! Siue effects: livei uamage, incieaseu iisk of piostate cancei, infeitility

:/03+1/9
! Remembei that its is the piimaiy hoimone ieleaseu uuiing stiess anu will ST0NT giowth
unuei stiessful conuitions
! i.e. inhibits BNA synthesis, inuuces piotein catabolism, inhibits bone giowth
! Auministiation of glucocoiticoius foi theiapy of asthma oi othei uisoiueis may
tempoiaiily ueciease lineai giowth in chiluien

C)*(0#F<9-$<&'$J+F<&/+.0
! =<G.#: excess amounts of uB, uue to tumois in anteiioi pituitaiy
! These tumois aie slow giowing anu seciete uB at veiy high iates
! If tumoi aiises befoie pubeity, when epiphyseal plates aie still open = F+F<&/+.0
! If tumoi aiises aftei pubeity, when lineai giowth is no longei possible = <)*(0#F<9-
Aciomegaly - no height expansion, only thickening of bones in hanus, feet anu heau
Thickening of the jaw = 1*(F&</"+.0
Also enlaiges the heait anu inteifeies with noimal functioning
! uB also has metabolic actions on bloou sugai levels anu bloou fatty aciu levels
! Najoi iole of uB in metabolism is to inciease these levels
! Theiefoie one way to inciease uB levels in noimal auult is loweiing of bloou sugai oi
fatty acius; uB levels will ietuin to baseline once these aie iestoieu
! In aciomegaly, uB levels aie always elevateu; thus it is associateu with elevateu plasma
levels of glucose anu fatty acius
! !*#</0#&/H of gigantism anu aciomegaly is to suigically iemove the pituitaiy tumoi
! If suigeiy is unsuccessful " long-teim auministiation of somatostatin


%&'()*+&#$=(&/*(9$(:$=<
XY
;(0#(./<.+.

! Nany hoimones, although impoitant i.e. giowth aie not necessaiy foi suivival
! Ca
2+
balance howevei is essential, the absence of it is uetiimental
! i.e. low plasma calcium incieases excitability of neive anu muscle plasma membianes
! i.e. high plasma calcium causes caiuiac aiihythmias anu uepiesseu neuiomusculai
excitability (fiom its effects on membiane potential)

%::#)/(*$.+/#.$:(*$=<9)+G0$"(0#(./<.+.$
! Calcium balance uepenus on the bone, kiuneys, anu gastiointestinal tiact
! Activities of gastiointestinal tiact anu kiuneys ueteimine the net intake anu output of
calcium foi the entiie bouy
! In contiast inteichanges of Ca between extiacellulai fluiu anu bone uo not altei total bouy
balance

W/,-
! 99% Ca is founu in bone
! composeu of connective tissue maue of seveial cell types suiiounueu by a collagen
matiix, calleu (./#(+' (wheie mineials aie uepositeu i.e. hyuioxyapatites)
! Some bones have maiiow cavity wheie bloou cells foim
! 1S of bone is osteoiu anu 2S mineial
! Cells involveu: (./#(I9<./.@$(./#()9<./.@$anu (./#()-/#.
! 0steoblasts - aie bone-foiming cells; seciete collagen to foim a matiix, which becomes
calcifieu (mineializeu); once suiiounueu by the calcifieu matiix they become.
! 0steocytes - have long cytoplasmic piocesses that extenu thioughout the bone anu foim
tight junctions with othei osteocytes
! 0steoclasts - laige, multinucleateu cells that bieak uown (iesoib) pieviously foimeu
bone by secieting B ions, which uissolve the ciystals, anu hyuiolytic enzymes, which
uigest the osteoiu
! Bone is always iemoueleu thioughout life by these cells: osteoclasts iesoib olu bone anu
osteoblasts lay uown a new matiix etc.
! This piocess uepenus on stiesses on the bouy i.e. exeicise, giavity
! Paiathyioiu hoimone is the piimaiy hoimone that iegulates Ca levels

Y+4,-B1
! Kiuneys filtei the bloou in oiuei to eliminate soluble wastes
! Amount of Ca excieteu by kiuneys is the uiffeience between the amount filteieu anu
iecaptuieu (ieabsoibeu)
! Reabsoiption uecieases when plasma Ca incieases anu incieases when plasma Ca
uecieases
! Boimonal contiolleis of Ca also iegulate phosphate balance

<5130/+,3-13+,59#305@3
! Absoiption of Na anu K is 1uu%
! Consiueiable amount of ingesteu Ca is not absoibeu anu simple leaves the bouy with
feces
! Boimones also contiol the active tianspoit system that achieves calcium absoiption
! i.e. incieases oi uecieases can occui in the amount of calcium absoibeu fiom the uiet

;(*0(&<9$=(&/*(9.
! 1<*</"-*(+'$"(*0(&#
! 4@X76'+"-'*(M-K+/<0+&$B

250538B0/+4#8/0*/,-
! Bone, kiuneys, anu gastiointestinal tiact aie contiolleu by PTB
! Paiathyioiu glanus, which seciete PTB, aie in the neck, embeuueu in the posteiioi
aspects of the thyioiu glanu
! The glanus aie uistinct
! PTB piouuction is contiolleu by extiacellulai Ca concentiation acting uiiectly on
secietoiy cells
! Becieaseu plasma calcium concentiation stimulates paiathyioiu hoimone secietion anu
vice veisa
! Functions of PTB:
1. Biiectly incieases iesoiption of bone by osteoclasts anu incieases plasma Ca
2. Stimulates the foimation of 1,2S-uihyuioxyvitamin B (which incieases intestinal
absoiption of Ca anu phosphate), thus the PTB effect on gastiointestinal tiact is
inuiiect
S. Biiectly incieases Ca ieabsoiption in kiuneys " uecieasing uiinaiy Ca concentiation
4. Biiectly ieuuces the ieabsoiption of phosphate in kiuneys, iaising uiinaiy
concentiation of phosphate

HRKP@.10/.#"3/E1)-$1%'6
! vitamin B is a gioup of compounus
! i.e. vitamin BS (cholecalcifeiol) foimeu by 0v fiom cholesteiol ueiivative in skin
! i.e. vitamin B2 (eigocalcifeiol) ueiiveu fiom plants
! vitamin B bioken uown in the livei by enzyme 2S-hyuioxylase anu then in kiuney cells by
1-hyuioxylase to foim 1,2S-uihyuioxyvitamin B (calcitiiol)
! It is a hoimone
! Stimulates absoiption of Ca in intestinal tiact
! i.e. uecieaseu vitamin B = uecieaseu plasma Ca = BAB
! Note that a ueciease in plasma Ca stimulates secietion of PTB anu thus moie 1,2S-(0B)2B
is foimeu
5-2+1)"%1%
! Calcitonin is a peptiue hoimone secieteu by cells (1<*<:(99+)G9<*$)#99.) in thyioiu glanus
(that aie uistinct fiom thyioiu follicles)
! Calcitonin uecieases plasma Ca by ieuucing bone iesoiption (inhibits osteoclasts)

V-35E/9+@#W/,-#Z+1-51-1#

! These uiseases ieflect pooi bone metabolism
! V+)S#/. (in chiluien) anu (./#(0<9<)+< (in auults) aie conuitions wheie mineialization of
bone matiix is ueficient
! Causes bone to be soft anu easily fiactuieu
! =<G.#: vitamin B ueficiency

! In contiast to these, (./#(1(*(.+., both mineials anu matiix aie lost uue to an imbalance
between bone iesoiption anu bone foimation
! =<G.#: excessive hoimonal concentiation that favois bone iesoiption anu highly ueficient
plasma Ca
! Commonly seen in aging anu moie common in women (smallei bone mass to begin with
anu menopause iemoves the bone-piomoting influence of estiogen)
! !*#</0#&/: postmenopausal women: estiogen oi its synthetic analogs, iegulai weight
beaiing exeicises (biisk walking oi staii climbing); uiugs - I+.1"(.1"</#. (inteifeie with
iesoiption of osteoclasts), .#9#)/+K#$#./*(F#&$*#)#1/(*$0('G9</(*.$[,%VT.M - inteiact
with estiogen anu compensates foi loss of estiogen

.B!-0@59@-*+5#
#
Piimaiy hypeipaiathyioiuism
! =<G.#H benign tumoi (auenoma) of one of the foui paiathyioiu glanus
! Tumois aie uniesponsive to extiacellulai Ca anu excietes PTB in excess
! %::#)/.H$incieaseu calcium iesoiption fiom bone, incieaseu kiuney ieabsoiption of Ca anu
incieaseu piouuction of 1,2S-(0B)2B fiom kiuney
! !*#</0#&/: suigical iemoval of paiathyioiu tumoi

Bumoial hypeicalcemia of malignancy
! =<G.#H cancei
! The cause of hypeicalcemia is often the ielease of a molecule that is chemically similai to
PTB - 8!;6*#9</#'$1#1/+'#$A8!;*1D, which is piouuceu by ceitain types of canceious
cells
! PTB ielease is uecieaseu uu to hypeicalcemia causeu by PTBip
! !*#</0#&/: tieat the cancei that is ieleasing PTBip; uiugs like bisphosphonates that
ueciease bone iesoiption

! Excessive ingestion of vitamin B = hypeicalcemia uespite low PTB levels
! ,-01/(0.$of hypeicalcemia: tiieuness anu lethaigy with muscle weakness as well as
nausea anu vomiting (uue to effects on uI tiact)



.B!/@59@-*+5

Piimaiy hypopaiathyioiuism
! =<G.#: iemoval of paiathyioiu glanus (fiom the tieatment of thyioiu uisease foi example)
! Low PTB = uecieaseu 1,2S-(0B)2B fiom kiuney
! Becieases in bone iesoiption, kiuney Ca ieabsoiption, anu uI Ca absoiption
! Pseuuohypopaiathyioiuism
! Resistance to the effects of PTB in taiget tissue leaus to sympmtoms of
hypopaiathyioiuism

Seconuaiy hypeipaiathyioiuism
! =<G.#: failuie to absoib vitamin B fiom uI tiact oi uecieaseu kiuney 1,2S-(0B)2B (kiuney
uisease)
! Becieaseu plasma Ca fiom uecieaseu uI absoiption iesults in stimulation of paiathyioiu
glanus
! ,-01/(0.: effects on excitable tissues " incieases the excitability of neives anu
muscles, which leaus to CNS effects (seizuies), muscles spasms ("-1()<9)#0+)$/#/<&-)
anu neive excitability
! !*#</0#&/: supplemental uietaiy Ca anu high uoses of uietaiy vitamin B (consumeu oi
injections)
Note that 1,25 (OH)D has a SIGNIFICANT effect on Ca levels
if there is failure to absorb vitamin D from GI tract, it leads to decreased kidney 1,25 OH and
significant loss of calcium plasma, DESPITE INCREASED PTH (due to low Ca levels)
- This is because your are MISSING the absorptions of Ca from BOTH kidney and GI tract
Note: if there is increased PTH wouldn't that lead to more bone resporption as well?