Introduction to Endocrinology

The Endocrine System - an integrated network of multiple

organs of various embryologic origins, that release hormones
ranging from small peptides to glycoproteins, which exert their
effects in the vicinity or in distant target cells. .

Hormone
Chemical substance produced and secreted by one cell
that travels through the blood to act on another cell.
Hormones can also be secreted into the extracellular
fluid and act on a nearby cell (paracrine secretion)

Target organ - contains cells that express hormone

specific receptors and show a biologic response after
hormone binding.

The components of the endocrine

system
Endocrine glands
Hormones
Hormone transport pathways
Hormone receptors

Endocrine glands- the classic endocrine glands are

ductless and secret their chemical products
(hormones) into the interstitial space and from there
into the circulation; they are not anatomically
connected and are scattered throughout the body.

Hypothalamus
Location:

Diencephalon,
integrated part of the
nervous system
Hormones: Releasing and
inhibiting
hormones;
ADH, oxytocin.

Hypothalamus and anterior pituitary

relationship
releasing hormones
inhibiting hormones

The Pituitary Gland (Hypophysis)

Secretes nine major hormones
Attached to the hypothalamus

by

the

infundibulum
Two parts:
Anterior pituitary gland (adenohypophysis)
Posterior pituitary gland (neurohypophysis)

Thyroid gland
located in the anterior neck

in front of the trachea.

weighs 10-25g;
consists of two
lobes,
connected by an isthmus.
A pyramidal lobe may be
present, arising from the
upper isthmus

Parathyroid glands
Usually four; rice grain

size;
located at the top and
bottom of posterior faces
of the thyroid lobes;
May be many, located
up to mediastinum

Endocrine Pancreas

The Adrenal Gland

Located above the kidneys, small, averaging

1-1.5 cm in lengh.
The right adrenal has a triangular shape, the
left a semilunar shape
They are made of 2 different parts derived
from 2 distinct embryological origins: the
cortex and the medulla.

The Adrenal Gland

Female reproductive system

Ovaries-

oval-shaped
glands that are located a
sides of the uterus.
Secrete both estrogen
and progesterone;
Release ovules

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Male reproductive system

Testes

/
testicles:
produce spermatozoa
Secrete testosterone

Classification of hormones
According to their chemical structure:
Protein or peptide hormones
Steroid hormones
Amino acid- derived hormones
Eicosanoids (derived from polyunsaturated fatty

acids)

Classification of hormones
According to their properties:
Hydrophilic hormones- the majority of amines,
peptides and protein hormones. They bind to
membrane receptors.
Lipophilic hormones: steroids and thyroid hormones.

They bind to the intracellular (nuclear) receptors.

Hormones

Hypothalamic hormones
Hypophysiotropic neurohormones
GHRH (growth hormone-releasing hormone)
-stimulates the GH (growth hormone) secretion.
TRH (thyrotropin-releasing hormone) that is the
major hypothalamic factor regulating the TSH
secretion. It also has an stimulatory effect on PRL
(prolactin) secretion
GnRH (gonadotropin-releasing hormone) - controls
the secretion of both LH and FSH.

Hypothalamic hormones
Hypophysiotropic neurohormones
Dopamine - the main inhibitor of PRL (prolactine)
CRH (corticotropin-releasing factor) that stimulates
the secretion of ACTH and other products of its
precursor molecule.
Somatostatin - inhibits the secretion of GH, TSH and
ACTH.

Hypothalamic hormones
Neurohormones are released from the posterior
pituitary (neurohypophysis):
Vasopressin or antidiuretic hormone (ADH) or

arginine- vasopressin (AVP)

Oxitocin

Pituitary hormones

Peptidic hormones
GH
ACTH
MSH
PRL

Peptidic hormones
Growth hormone
The main physiologic effect is to regulate growth
(overall anabolic effects).
Stimulates the hepatic production of IGF-1 (insulin-

like growth factor)

Peptidic hormones
Adrenocorticotropic hormone
ACTH stimulates the production and release of
glucocorticoids (cortisol) ans weak androgens from
the adrenal cortex;
Mineralocorticoid secretion is under the control of RAA
(renin-angiotensin-aldosteron) system.

Peptidic hormones
MSH - Melanocyte-stimulating hormone
Increases melanin synthesis in melanocytes.
Has structure similarities to ACTH
Both hormones have a common precursor (POMC

pro-opio-melanocortin)

Peptidic hormones
Prolactin
The main physiologic effects of PRL are stimulation
of growth and development of the mammary gland,
synthesis of milk and maintenance of milk secretion;
Prolactin also modulates reproductive and parental
behavior.
In excess, PRL inhibits LH and FSH;

Glycoproteic hormones
TSH
FSH
LH

Glycoproteic hormones
Thyroid- stimulating hormone (TSH)
Stimulates all the events involved in thyroid hormone

synthesis and release.

In addition, it acts as a growth factor for the thyroid

gland.

Glycoproteic hormones
Gonadotropins (LH and FSH)
stimulate sex hormones synthesis,
Stimulate spermatogenesis,
Stimulate folliculogenesis and ovulation.
Their central role is the control of reproductive

function in both males and females.

Thyroid hormone synthesis

The production and the release of thyroid hormones are
under negative feedback regulation by the
hypothalamic- pituitary- thyroid axis.

Thyroid hormones play important roles in maintaining

energy homeostsis and regulating energy expenditure.

Their primary physiologic effects are to stimulate cell

metabolism and activity.

They have a vital role in the

development,
differentiation and maturation of fetus during gestation.

Parathyroid hormone synthesis

The main physiologic effects of PTH (parathyroid

hormone) is to regulate plasma calcium levels.

It acts in relation with other hormones:

- vitamin D
- calcitonin (produced in the parafollicular C cells
of the thyroid)

Hormones of the adrenal cortex

The adrenal synthesis starts with cholesterol which is

converted to pregnenolone.
The hormones produced by the human adrenal glands

are called steroid hormones.

The adrenal cortex contains 3 zones that vary in the

steroid hormones production :
Zona glomerulosa- mineralocorticoids
Zona fasciculata- glucocorticoids, cortisol and

corticosterone and androgens (DHEA and DHEAS)

Zona reticularis- androgens; it also produces

glucocorticoids

The general metabolic effects, sexual effects, cardiovascular effects, etc. of the steroid hormones make
them absolutely necessary for living.

Hormones of the adrenal medulla

The medulla is the central part of the adrenal gland.
It produces catecholamines
norepinephrine
epinephrine and,
to a lesser extent, dopamine)

The response to stress consists of close interaction

between the steroid hormones and catecholamines
to ensure adequate fuel metabolism and hemodynamic
control.

Gonadal hormone synthesis

The testis produces:
Testosterone,

androstendione, estradiol
amounts) produced by the Leydig cells, and

(small

Inhibin and activins, produced and released from the

Sertoli cells.

Gonadal hormone synthesis

The ovary produces steroid hormones (progesteron,

estrogen and testosterone) and peptide hormones

(inhibins).
Estrogen - produced by the ovarian follicle.
Progesteron - produced by the corpus luteum

(remanent of the ovulatory follicle, after ovulation).

Hormonal transport
Secreted hormones move through the bloodstream to
endocrine target organs, which are often distant from
the initial site of hormone release.
This represents the most important way of hormone
transport.

Hormone transport in the circulation

There are two distinct transport ways:
The general bloodstream
The circulation at the hypothalmo-hypophyseal portal

system (both ways).

Hypothalmo-Hypophyseal Portal
System (Gr.T.Popa - Una Fielding)

Hormone receptors
Hormones produce their biologic effects by binding to
specific hormone receptors in target cells

Hormone receptors
Depending on their cellular localization, hormone
receptors can be classified as:
Membrane receptors that bind catecholamins,

peptides, proteic hormones and eicosanoids

Intracellular (nuclear) receptors that bind steroid

hormones, thyroid hormones and vitamin D.

Functioning of the endocrine system

A. Synthesis and storage of hormones

Any cell in the human body is able to synthesise

hormones.

On the other hand, endocrine tissue:

- synthesizes a bigger amount than the nonendocrine
tissue
- is able to convert prohormones to hormones
- releases hormones into the bloodstream constantly

Synthesis and storage of hormones

1. Peptide hormones

- are synthesized as prohormones and undergo posttranslational processing.

- they are stored in secretory granules before being
released by exocytosis

Synthesis and storage of hormones

2. Thyroid hormones - Synthesis of thyroid hormones
by the thyroid gland involves major steps:
- active transport of iodide across the basement
membrane into the thyroid cell (trapping)
- oxidation of iodide and iodination of thyrosyl
residues in thyroglobulin (organification)

Synthesis and storage of hormones

- connection of iodotyrosine molecules within
thyroglobulin to form the iodothyronines T3 and T4
(coupling)
- protheolysis of thyroglobulin, with consequent
release of free iodothyronines and iodotyrosines
within the thyroid cell, with conservation and reuse of
the liberated iodide
- intrathyroidal 5-deiodination of T4 and T3.

Synthesis and storage of hormones

3. Steroid hormones
Steroid hormones are produced mainly in:
- the adrenals,
- gonads,
- nervous system,
- other tissues, including adipocytes, placenta or
skin.

Synthesis and storage of hormones

Steroids are not stored in endocrine organs.
Hormone release is regulated at the level of synthesis.
Steroid hormones are derived from cholesterol via

action of a series of steroidogenic enzymes of the

cytochrome P450 class of oxidases.

Synthesis and storage of hormones

Synthesis and storage of hormones

4. Vitamin D3
Like steroids, vitamin D is derived from cholesterol.
Cholesterol is converted to 7- dehydrocholesterol and

then to cholecalciferol (vitamin D3) in skin in

response to sun light.

Synthesis and storage of hormones

Synthesis and storage of hormones

5. Catecholamines
Synthesis starts from phenylalanine.
Cytosolic catecholamines are loaded into secretory

granules and released when needed.

Synthesis and storage of hormones

6. Eicosanoids
Are mostly derived from
arachidonic acid, which
in turn is synthesized
from essential fatty acids
stored in the cell
membranes.

Synthesis and storage of hormones

6. Eicosanoids
Their actions are paracrine and autocrine and they have
renal, gonadic, pituitary actions.

Synthesis and storage of hormones

Hormone storage:
in secretory granules (peptidic hormones),
in the follicular colloid (thyroid hormones),
in intracellular vesicles (steroid hormones)
synaptic vesicles (catecholamines),
hepatic and renal (vitamin D).

Regulation of hormonal production

At the level of transcription (genic):

- posttranscriptional mechanism
- translation efficiency
At the level of release (feed- back)

Endocrine feedback (in thyroid

hormones)

Hormone transport

Hormone transport
Lipophilic hormones (steroid, thyroid hormones)
bound to specific proteins
Albumines and prealbumines
Specific

globulines (TBG thyroxin binding

globulin; SHBG sex-hormone binding globulin;
CBG corticosteroid binding globulin).
Unbound (free)

Hormone transport
Hidrophilic hormones (peptidic hormones and
catecholamines) are transported unbound, excepting
for CRH and GH, partialy bound.

Metabolism and elimination of

hormones

Metabolism and elimination of

hormones
Peptide hormones

Most of them have short half-life in the circulation

(few minutes).
The

major mechanism for peptide hormone

degradation is via binding to cell surface receptors and
non- receptor hormone- binding sites, with subsequent
internalization and degradation in the cell (lysosome).

Metabolism and elimination of

hormones
Thyroid hormones

Have relatively long half-life in the circulation (about

7 days for T4 and 1 day for T3).

Thyroid

hormones are subject to multiple

deiodinations by at least three different deiodinases,
whose levels vary in different tissues.

Metabolism and elimination of

hormones
Cathecolamines

Have a half- life of about two minutes.

Are degradated by two principal routes:
- Catechol-O- methyltransferase (COMT), producing

normetanephrine and metanephrine.

- Mono-amine oxidase (MAO), producing vanilmandelic acid (VMA).

Metabolism and elimination of

hormones
Steroid hormones
Cortisol and aldosteron are metabolised in the liver
Androgens are also metabolised in the

liver

Physiologic functions and the role

of hormones

Regulation of sodium and water balance and control

of blood volume and presure

Regulation of calcium and phosphate balance to

preserve extracellular fluid concentrations required for

cell membrane integrity and intracellular signaling

Regulation of energy balance and control of fuel

metabolism,
Coordination of the host hemodynamic and metabolic

counterregulatory responses to stress

Regulation of reproduction, development, growth and

senescence.

Disorders of the endocrine system

Disorders of the endocrine system

Functional disorders:
Decreased hormonal production
Increased hormonal production
Abnormal hormonal production, with abnormal
effects
Receptor resistance to hormonal action
Defects in transportation or metabolisation
Complex disordes (association of hypo/
hyperfunction on different hormonal lines).

Disorders of the endocrine system

Morphologic disorders:
with or without functional endocrine consequences,
posible
associated
disorders
(neurological,
ophtalmologic, respiratory).