lecture 1, introduction to endocrinology

8/17/2019 Lecture 1, Introduction to Endocrinology

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Introduction to Endocrinology

The Endocrine System - an integrated network of multipleorgans of various embryologic origins, that release hormones ranging from small peptides to glycoproteins, which exert theireffects in the vicinity or in distant target cells. .


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Hormone

Chemical substance produced and secreted by one cellthat travels through the blood to act on another cell.

Hormones can also be secreted into the extracellularfluid and act on a nearby cell (paracrine secretion)


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Target organ - contains cells that express hormonespecific receptors and show a biologic response after

hormone binding.


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The components of the endocrine

system

ndocrine glandsHormones

Hormone transport pathways

Hormone receptors


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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.


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Hypothalamus

"ocation# $iencephalon,

integrated part of thenervous system

Hormones# %eleasing and

inhibiting hormones!

&$H, oxytocin.


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Hypothalamus and anterior pituitary

relationship

releasing hormones

inhibiting hormones


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The 'ituitary land (Hypophysis)

ecretes nine ma*or hormones

&ttached to the hypothalamus by theinfundibulum

Two parts#

&nterior pituitary gland (adenohypophysis)'osterior pituitary gland (neurohypophysis)


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Thyroid gland

located in the anterior neck

in front of the trachea.weighs +-/g!

consists of two lobes,

connected by an isthmus.

& pyramidal lobe may be

present, arising from the

upper isthmus


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'arathyroid glands

0sually four! rice grain

si1e!located at the top and

bottom of posterior faces

of the thyroid lobes!

2ay be many, located

up to mediastinum


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ndocrine 'ancreas


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The &drenal land

Located above the kidneys, small, averaging1-1.5 cm in lengh.

The right adrenal has a triangular shape, theleft a semilunar shape

They are made of 2 dierent parts derivedfrom 2 distinct embryological origins! thecorte" and the medulla.


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The &drenal land


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3emale reproductive system

Ovaries- oval-shaped

glands that are located a

sides of the uterus.

ecrete both estrogen

and progesterone!

%elease ovules

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2ale reproductive system

Testes / testicles#

produce spermato1oa

ecrete testosterone


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Classification of hormonesAccording to their chemical structure#

'rotein or peptide hormones

teroid hormones

&mino acid- derived hormones

icosanoids (derived from polyunsaturated fatty

acids)


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Classification of hormones

According to their properties#

Hydrophilic hormones- the ma*ority of amines, peptides and protein hormones. They bind to

membrane receptors.

"ipophilic hormones# steroids and thyroid hormones.

They bind to the intracellular (nuclear) receptors


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Hormones


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Hypothalamic hormones!ypophysiotropic neurohormones

"!#! (growth hormone-releasing hormone)

-stimulates the H (growth hormone) secretion.T#! (thyrotropin-releasing hormone) that is the

ma*or hypothalamic factor regulating the TH

secretion. 4t also has an stimulatory effect on '%"

(prolactin) secretion

"n#! (gonadotropin-releasing hormone) - controls

the secretion of both "H and 3H.


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Hypothalamic hormones!ypophysiotropic neurohormones

$opamine - the main inhibitor of '%" (prolactine)

C%H (corticotropin-releasing factor) that stimulatesthe secretion of &CTH and other products of its

precursor molecule.

omatostatin - inhibits the secretion of H, TH and

&CTH.


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Hypothalamic hormones$eurohormones are released from the posterior

pituitary (neurohypophysis)%

5asopressin or antidiuretic hormone (&$H) or

arginine- vasopressin (&5')

6xitocin


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'ituitary hormones


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%eptidic hormones

&H'(TH

)*H

%+L


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'eptidic hormones

"ro&th hormone

The main physiologic effect is to regulate growth(overall anabolic effects).

timulates the hepatic production of 43-+ (insulin-like growth factor)


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'eptidic hormones

Adrenocorticotropic hormone

&CTH stimulates the production and release of

glucocorticoids (cortisol) ans weak androgens from

the adrenal cortex!

2ineralocorticoid secretion is under the control of %&&

(renin-angiotensin-aldosteron) system.


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'eptidic hormones

'S! - 'elanocyte-stimulating hormone

4ncreases melanin synthesis in melanocytes.

Has structure similarities to &CTH7oth hormones have a common precursor ('62C 8

pro-opio-melanocortin)


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'eptidic hormones

rolactin

The main physiologic effects of '%" are stimulationof growth and development of the mammary gland,

synthesis of milk and maintenance of milk secretion!

'rolactin also modulates reproductive and parental

behavior.

4n excess, '%" inhibits "H and 3H!


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&lycoproteic hormonesTSH

FSHLH


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lycoproteic hormonesThyroid- stimulating hormone (TS!)

timulates all the events involved in thyroid hormonesynthesis and release.

4n addition, it acts as a growth factor for the thyroidgland.


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lycoproteic hormones"onadotropins (! and *S!)

stimulate sex hormones synthesis,timulate spermatogenesis,

timulate folliculogenesis and ovulation.

Their central role is the control of reproductive

function in both males and females.


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Thyroid hormone synthesis

The production and the release of thyroid hormones areunder negative feedback regulation by the

hypothalamic- pituitary- thyroid axis.


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Thyroid hormones play important roles in maintainingenergy homeostsis and regulating energy expenditure.

Their primary physiologic effects are to stimulate cellmetabolism and activity.

They have a vital role in the development,

differentiation and maturation of fetus during gestation.


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'arathyroid hormone synthesis

The main physiologic effects of 'TH (parathyroid

hormone) is to regulate plasma calcium levels.

4t acts in relation with other hormones#

- vitamin $- calcitonin (produced in the parafollicular C cells

of the thyroid)


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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.


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The adrenal cortex contains 9 1ones that vary in thesteroid hormones production #

+ona glomerulosa- mineralocorticoids

+ona fasciculata- glucocorticoids, cortisol and

corticosterone and androgens ($H& and $H&)

+ona reticularis- androgens! it also producesglucocorticoids


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The general metabolic effects, sexual effects, cardio-vascular effects, etc. of the steroid hormones make

them absolutely necessary for living.


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Hormones of the adrenal medullaThe medulla is the central part of the adrenal gland.

4t produces catecholamines norepinephrine

epinephrine and,

to a lesser extent, dopamine)


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The response to stress consists of close interaction

between the steroid hormones and catecholamines to ensure ade:uate fuel metabolism and hemodynamic

control.


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onadal hormone synthesis

The testis produces#

Testosterone, androstendione, estradiol (smallamounts) produced by the "eydig cells, and

4nhibin and activins, produced and released from theertoli cells.


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onadal hormone synthesisThe ovary produces steroid hormones (progesteron,

estrogen and testosterone) and peptide hormones

(inhibins).

strogen - produced by the ovarian follicle.

'rogesteron - produced by the corpus luteum

(remanent of the ovulatory follicle, after ovulation).


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Hormonal transport

ecreted hormones move through the bloodstream to

endocrine target organs, which are often distant fromthe initial site of hormone release.

This represents the most important way of hormone

transport.


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Hormone transport in the circulation

There are two distinct transport ways#

The general bloodstream

The circulation at the hypothalmo-hypophyseal portalsystem (both ways).


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Hypothalmo-Hypophyseal 'ortal

ystem (r.T.'opa - 0na 3ielding)


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Hormone receptors

Hormones produce their biologic effects by binding to

specific hormone receptors in target cells


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Hormone receptors$epending on their cellular locali1ation, hormone

receptors can be classified as#

'embrane receptors that bind catecholamins,

peptides, proteic hormones and eicosanoids

Intracellular (nuclear) receptors that bind steroid

hormones, thyroid hormones and vitamin $.


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3unctioning of the endocrine system


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&. ynthesis and storage of hormones


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&ny cell in the human body is able to synthesise

hormones.


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6n the other hand, endocrine tissue#

- synthesi1es a bigger amount than the nonendocrine

tissue

- is able to convert prohormones to hormones

- releases hormones into the bloodstream constantly


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ynthesis and storage of hormones

, eptide hormones

- are synthesi1ed as prohormones and undergo post-

translational processing.

- they are stored in secretory granules before being

released by exocytosis


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ynthesis and storage of hormones Thyroid hormones - ynthesis of thyroid hormones

by the thyroid gland involves ma*or steps#

- active transport of iodide across the basementmembrane into the thyroid cell (trapping)

- oxidation of iodide and iodination of thyrosyl

residues in thyroglobulin (organification)


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ynthesis and storage of hormones- connection of iodotyrosine molecules within

thyroglobulin to form the iodothyronines T9 and T;

(coupling)

- protheolysis of thyroglobulin, with conse:uent

release of free iodothyronines and iodotyrosines

within the thyroid cell, with conservation and reuse of

the liberated iodide- intrathyroidal /


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ynthesis and storage of hormones9. Steroid hormones

teroid hormones are produced mainly in#

- the adrenals,- gonads,

- nervous system,

- other tissues, including adipocytes, placenta orskin.


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ynthesis and storage of hormonesteroids are not stored in endocrine organs.

Hormone release is regulated at the level of synthesis.

teroid hormones are derived from cholesterol via

action of a series of steroidogenic en1ymes of the

cytochrome ';/ class of oxidases.


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ynthesis and storage of hormones;. .itamin 0

"ike steroids, vitamin $ is derived from cholesterol.

Cholesterol is converted to =- dehydrocholesterol and

then to cholecalciferol (vitamin $9) in skin in

response to sun light.


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ynthesis and storage of hormones/. 1atecholamines

ynthesis starts from phenylalanine.

Cytosolic catecholamines are loaded into secretory

granules and released when needed.


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>. Eicosanoids

&re mostly derived from

arachidonic acid, which

in turn is synthesi1ed

from essential fatty acids

stored in the cell

membranes.


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>. Eicosanoids

Their actions are paracrine and autocrine and they have

renal, gonadic, pituitary actions.


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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 $).


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%egulation of hormonal production

&t the level of transcription (genic)#

- posttranscriptional mechanism- translation efficiency

&t the level of release (feedback)

ndocrine feedback (in thyroid


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( y

hormones)


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Hormone transport


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Hormone transportipophilic hormones (steroid, thyroid hormones)

bound to specific proteins

&lbumines and prealbumines

pecific globulines (T7 8 thyroxin binding

globulin! H7 8 sex-hormone binding globulin!

C7 8 corticosteroid binding globulin).

0nbound (free)


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Hormone transport

!idrophilic hormones (peptidic hormones and

catecholamines) are transported unbound, excepting

for C%H and H, partialy bound.


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2etabolism and elimination of

hormones


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hormoneseptide hormones

2ost of them have short half-life in the circulation(few minutes).

The ma*or mechanism for peptide hormone

degradation is via binding to cell surface receptors and

non- receptor hormone- binding sites, with subse:uent

internali1ation and degradation in the cell (lysosome).


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hormonesThyroid hormones

Have relatively long half-life in the circulation (about= days for T; and + day for T9).

Thyroid hormones are sub*ect to multiple

deiodinations by at least three different deiodinases,

whose levels vary in different tissues.


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hormones1athecolamines

Have a half- life of about two minutes.

&re degradated by two principal routes#

- Catechol-6- methyltransferase (C62T), producing

normetanephrine and metanephrine.

- 2ono-amine oxidase (2&6), producing vanil-

mandelic acid (52&).


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hormones

Steroid hormones

Cortisol and aldosteron are metabolised in the liver

'ndrogens are also metabolised in theliver


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'hysiologic functions and the role

of hormones


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%egulation of sodium and water balance and control

of blood volume and presure

%egulation of calcium and phosphate balance to

preserve extracellular fluid concentrations re:uired for

cell membrane integrity and intracellular signaling


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%egulation of energy balance and control of fuel

metabolism,

Coordination of the host hemodynamic and metabolic

counterregulatory responses to stress

%egulation of reproduction, development, growth and

senescence.


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$isorders of the endocrine system


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$isorders of the endocrine system*unctional disorders%

$ecreased hormonal production

4ncreased hormonal production

&bnormal hormonal production, with abnormaleffects

%eceptor resistance to hormonal action

$efects in transportation or metabolisationComplex disordes (association of hypo?

hyperfunction on different hormonal lines).


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$isorders of the endocrine system

'orphologic disorders%with or without functional endocrine conse:uences,

posible associated disorders (neurological,

ophtalmologic, respiratory).

lecture 1, introduction to endocrinology

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