Review of Endocrine System

Endocrine System Endocrine System

Hypofunction Hyperfunction
Inputs
Over inhibition Over stimulation
Hyperplasia
Destruction Endocrine gland Tumor / Cancer
Prohormone biosynthesis

Hormone processing

Storage
Secretion

Transportation
Degradation in blood Degradation
Excretion Target cell Excretion
Antagonist Receptor Agonist

Inhibition Effector Stimulation

1
Response
 Know Major Hormone Signal
p 674 Transduction Pathways

2
Unit 2
Hypothalamus & Pituitary:
Neuroendocrinology
I. Central endocrine organs
– Hypothalamus
– Anterior pituitary
– Posterior pituitary
– Pineal
II. Hypothalamus - Anterior Pituitary - Target System
III. Hypothalamus + Posterior Pituitary - Target System
IV. Biological Rhythms

Readings: p670 - 677, p685-689 3

Learning Objectives
By the end of this lecture you will learn about:
• The basic neuroanatomy and function of the hypothalamus and
pituitary – the central endocrine organs.
• The definition of neuroendocrinology.
• The hypothalamic-pituitary anatomical & functional links.
• Understand posterior pituitary hormones and their functions.
• Know all of the hypothalamic releasing/inhibiting hormones, their
corresponding pituitary hormones, and corresponding target
hormones – by abbreviation and by full name(s)!
• Learn more about negative feedback.
• Learn about biological rhythms controlled by hypothalamus and
pineal hormones.

4
 I. Central Endocrine Organs
• Brain (hypothalamus)
– Releasing/inhibiting hormones
– Functions include reproduction, lactation, thyroid/metabolism,
growth, stress
• Anterior pituitary
– Has corresponding hormones to each hypothalamic hormone
• Posterior pituitary
– Water balance, milk ejection
• Pineal
– Biological rhythms

5
Neuroanatomy of the
Central Endocrine Organs

Pineal

Hypothalamus

Pituitary

6
What is Neuroendocrinology?

• Link between nervous and endocrine

systems.
• Primary driving force is typically the nervous
system; the endocrine system responds to
nervous system signal; the endocrine system
feedback to nervous system.
• Often a single cell can have both neuronal
and endocrine qualities.
• Example: The hypothalamus.

7
Overview of Hypothalams Neuroendocrine System

Pay a@enAon to feedback
regulaAon at
hypothalamus & pituitary

From AC Gore,
Fundamental Neuroscience
Vol 3, Ed. Squire et al, 2008
8
Anatomical Relationship Between
Hypothalamus & Pituitary

9
 Pituitary (Anterior & Posterior)
• Hypophysis
• Small gland located in bony cavity just below
hypothalamus
– Thin stalk connects pituitary gland to hypothalamus
{infundibulum; pituitary stalk}
• Consists of two anatomically and functionally distinct
lobes
– Anterior pituitary (adenohypophysis)
• Consists of glandular epithelial tissue {Develops from Rathke’s
pouch}
– Posterior pituitary (neurohypophysis)
• Composed of nervous tissue
10
 Hypothalamus Hypothalamus
Anterior Pituitary Posterior Pituitary
Fig 18‐5, p 671
Fig 18‐8, p 676

AKA: Portal Capillary Vasculature 11
 Anterior Pituitary Posterior Pituitary
Cells Neuroterminals
Capillary

Nucleus

Secretory Secretory
vesicles in Extracellular vesicles in
cytoplasm space nerve terminals

12
Electron microscopy (TEM) images of pituitary from a female rat
II. Hypothalamus - Anterior Pituitary -Target System
Hypothalamic hormones involved in anterior pituitary
regulation are tropic hormones
•Stimulate/inhibit hormone secretion of another
endocrine gland (Anterior pituitary)
•Stimulates and maintains the target function.
Most anterior pituitary hormones are tropic hormones
•Stimulate/inhibit hormone secretion of another
endocrine gland (Target organ, e.g., thyroid gland,
testis).
•Stimulates and maintains their target functions.
•Loss of secretion of a tropic hormone results in
hypotrophy/atrophy of the target.
13
Vascular Link Between Hypothalamus &
Anterior Pituitary
Fig 18-8, p 676

14
Hypothalamic Releasing & Inhibiting Hormones
Table 18-4, p 674
Hormone
SecreAon of each anterior
pituitary hormone is
Thyrotropin-Releasing
sAmulated or inhibited by hormone (TRH)
one or more hypothalamic
hypophysiotropic hormones Corticotropin-Releasing
hormone (CRH)
Gonadotropin-releasing
hormone (GnRH)
Growth-hormone releasing
hormone (GHRH)
Somatostatin (Growth-
hormone inhibiting hormone;
GHIH)
Not identified yet Prolactin-releasing hormone
(PRH)
Dopamine (Prolactin-inhibiting Inhibits release of prolactin
hormone; PIH)
Effect on Anterior
Pituitary
Stimulates release of TSH
and prolactin
Stimulates release of ACTH
Stimulates release of FSH
and LH
Stimulates release of
growth hormone
Inhibits release of growth
hormone and TSH
Stimulates release of
prolactin
15
 Anterior Pituitary Synthesizes and Secrete 6
Different Protein (Peptide) Hormones
Tropic:
Thyroid-stimulating hormone(TSH): Stimulates secretion of thyroid hormone
Adrenocorticotropic homone (ACTH): Stimulates secretion of cortisol by adrenal cortex
Follicle-stimulating hormone (FSH): In females, stimulate growth and development of
ovarian follicles; promotes secretion of estrogen by ovaries. In males, required for
sperm production
Luteinizing hormone (LH): In females, responsible for ovulation and luteinization;
regulates ovarian secretion of female sex hormones. In males, stimulates
testosterone secretion.
Growth hormone (GH): Primary hormone responsible for regulating overall body growth;
involved in metabolism. Stimulates IGF-1 secretion.

Not Tropic:
Prolactin (PRL): Enhances breast development and milk production in female.

16
Targets of Anterior Pituitary Hormones
Fig 18-6, p 673

17
Regulation of Anterior Pituitary Gland
• Responds to hypothalamic releasing and
inhibiting hormones
• Also responds to feedback by target-gland
hormones

18
Links Between
Hypothalamic - Anterior Pituitary - Target Hormones
GnRH
CRH
TRH
GHRH/ss
PIH (DA)

LH/FSH
ACTH
TSH
GH
PRL

Sex steroid hormones
CorAsol (glucocorAcoids)
Thyroid hormones
IGF‐I (also growth)
Milk synthesis 19
More on Negative Feedback
Fig 18-7, p 675

20
 III. Hypothalamus + Posterior Pituitary -
Target System Fig 18‐5, p 671

1. The paraventricular and supraoptic

nuclei both contain neurons that
produce vasopressin and oxytocin. The
hormone, either vasopressin or oxytocin
depending on the neuron, is synthesized
in the neuronal cell body in the
hypothalamus.
2. The hormone travels down the axon to
be stored in the neuronal terminals
within the posterior pituitary.
3. When the neuron is excited, the stored
hormone is released from the terminals
into the systemic blood for distribution
throughout the body.
21
Posterior Pituitary

– Along with hypothalamus forms neuroendocrine

system
– Does not synthesize any hormones
– Store and release two small peptide hormones
• Vasopressin
– Conserves water during urine formation
• Oxytocin
– Stimulates uterine contraction during childbirth and milk
ejection during breast-feeding

22
 Vasopressin (VP)

• Also called ADH (anti-diuretic hormone) and

arginine vasopressin (AVP).
• Major function:
– Enhances water retention by the kidneys; it is
primary regulator of water balance in the body.
• Result is to cause changes in drinking and salt appetite.
– Works together with CRH on stress response.
– Arteriolar smooth muscle contraction (blood
pressure) - minor effect
• Regulated by osmoreceptors in hypothalamus,
that respond to a rise in plasma osmolarity (solute
concentration).
23
Oxytocin (OT)

• Stimulates uterine smooth muscle contraction

during childbirth.
• Promotes milk ejection from mammary glands
during suckling.
• Works together with prolactin on lactotropes.
• Involved in some behaviors including maternal
behavior and pair-bonding in monogamous
species.

24
 Vasopressin and Oxytocin
• They are synthesized off of genes located “head to head” in
opposite orientations.
• Each is nine amino acids (nonapeptide) and they are
structurally similar.
• Both are in cells that are relative large (20-40 um), known as
magnocellular neurons*.
• One type of OT receptor, on breast tissue, pituitary, brain,
uterus, arterioles.
• Three types of AVP receptors, on kidney, pituitary, brain.
• All receptors are G-protein coupled receptors.

*Contrast this with parvicellular (small) cells of hypothalamic

releasing/inhibiting neurons
25
 Vosopressin and Oxytocin Synthesis

Oxytocin gene Vasopressin gene
transcripAon transcripAon
Intergenic region

H2N Neurophysin COOH COOH Neurophysin NH2

Signal Signal
PepAde PepAde

Oxytocin Vasopressin

CYIQNCPLG CYFQNCPRG

26
 IV. Biological Rhythms
• Hypothalamus:
Suprachiasmatic nucleus (SCN) -- Neural control
• Pineal gland:
Melatonin -- Hormonal control

• Cycles of biological rhythms:

– Hourly (hormone pulses)
– Daily (circadian/diurnal)
– Weekly/monthly (estrous/menstrual)
– Yearly (seasonal)

27
 Metatonin
Pineal Gland
• Tiny, pinecone-shaped structure
• Located in center of brain
• Secretes melatonin, a tryptophan metabolite
– Hormone of darkness
• Secretion falls to low levels during light of day
– Functions
• Helps keep body’s circadian rhythms in synchrony with light-dark
cycle
• Promotes sleep
• Influences reproductive activity, including onset of puberty
• Acts as antioxidant to remove free radicals
• Enhances immunity

28
 Circadian Rhythms

• Suprachiasmatic nucleus (SCN)

– Part of hypothalamus
Fundamental Neuroscience, Vol 2 (2002)
– Body’s master biological clock
– Self-induced cyclic variations in clock protein
concentrations within SCN bring about cyclic changes
in neural discharge from SCN
• Cycle takes about a day
• Drives body’s circadian (daily) rhythms
– SCN must be set daily by external cues so body’s
biological rhythms are synchronized with activity levels
driven by surrounding environment

29
Circadian Rhythms
• Daily changes in light intensity
– Major environmental cue used to adjust SCN
master clock
– Photoreceptors in retina pick up light signals
and transmit them directly to SCN
– SCN relays message regarding light status to
pineal gland

30
Circadian (Diurnal) Rhythms of Hormones

From: Richter et al., Biological Research 37, 2004

31
Examples of Other Circadian Rhythms in Humans

Fundamental
Neuroscience,
Vol 2 (2002)

32