endocrine system 5 morphophysiology

8/12/2019 Endocrine system 5 Morphophysiology

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The Endocrine System

Basic

Morphophysiology

EMIS – ITESM

Department of BasicSciences



Introduction

• Maintenance of homeostasis involves

coordinating activities of organs and

systems throughout the body

• Endocrine system and Nervous system

are the mayor control systems



Introduction

• The Endocrine System is responsible for themaintenance of growth,metabolism,development, puberty

and mood.

• The endocrine andnervous system canwork together or alone to

perform the same generalfunctions: to monitor andadjust physiologicactivities



Introduction

Summary:

• Major control systems:

– Endocrine and nervous system work together – Function: to maintain homeostasis

• Both use

– specific communication methods – affect specific target organs

• Their methods and effects differ.



Introduction

• In general, the nervous system performs short-

term very specific responses to environmental

stimuli

- chemical messengers are neurotransmitters

• The endocrine system regulates longer-term,

ongoing metabolic processes throughout the

body- chemical messengers are hormones



Comparison of Nervous and Endocrine Systems Control

Characteristic Nervous System Endocrine System

Mediator Molecules Neurotransmitters – released locally

Hormones – deliveredthroughout the body

by the blood

Site of Mediator Action Close to site of

release

Usually far from site of

release

Types of target cells Muscle (smooth,

cardiac, and skeletal)

cells, gland cells,

other neurons

Cells throughout the

body

Time to onset of action Within milliseconds Seconds – hours -days

Duration of Action Typically briefer

(milliseconds)

Generally longer

(seconds to days)



Glands

A. Exocrine gland

– Ducts

– Lumen and

surfaces

B. Endocrine gland

– Chemical

messengers

– Blood stream



Endocrine System



Pituitary

• The hypothalamus-pituitary unit is the most dominantportion of the entire endocrine system.

• The output of the hypothalamus-pituitary unit regulates

the function of the thyroid, adrenal and reproductiveglands and also controls somatic growth, lactation,milk secretion and water metabolism.

• The pituitary gland lies in a pocket of bone at the base

of the brain, just below the hypothalamus to which it isconnected by a stalk containing nerve fibers and bloodvessels. The pituitary is composed to two lobes--anterior and posterior .



Pituitary



Pituitary

• Anterior pituitary derived

from outpouching of

pharyngeal mucosa

– Eventually pinches offand becomes separate

from pharynx

• Posterior pituitary derivedfrom outgrowth of

hypothalamus



Pituitary

Posterior pituitary remains connected to hypothalamus by infundibular stalk



Pituitary

The anterior,intermediate, andposterior lobes ofthe pituitary glandare actually threemore or lessseparate endocrineorgans.

The intermediate lobeis rudimentary inhumans. It is

separated from theanterior lobe by theremains of Rathke'spouch.



Gross Anatomy - Histological Organization of the Pituitary Gland



Anterior Pituitary

• All are peptide hormones

• All are trophic hormones: Stimulate a targetendocrine gland to secrete increased amountsof its own hormone (except PRL ).



Anterior PituitaryACTH, prolactin, and growth hormone are simple polypeptides or proteins.

TSH, LH, and FSH are glycoproteins made up of two subunits (α and β).

All of the α subunits of these hormones are products of a single gene andhave the same amino acid composition, although their carbohydrateresidues vary.

The β subunits, which are produced by separate genes and differ in structure,confer hormonal specificity. The α subunits are remarkablyinterchangeable, and hybrid molecules can be created.



Pituitary Hormones



Hypothalamic

Pituitary Axis



Pituitary Portal System

Hypothalamic-hypophyseal portalsystem links anterior pituitary tohypothalamus.

In most parts of the body, arteriesare connected with veinsthrough capillary plexus.Nonetheless, in certain areas,we can find special functionaladaptations to this system.

When capillaries connect withvessels that, in turn, offer asecond set of capillariesbefore connecting withsystemic veins, this dispositionis called a po rtal system .




Parvicellularneurosecretory cel ls secrete releasingfactors into capillaries

of the pituitary portalsystem at the medianeminence which arethen transported tothe anterior pituitarygland to regulate thesecretion of pituitaryhormones.




The anterior pituitary is made upof interlacing cell cords andan extensive network ofsinusoidal capillaries.

The endothelium of the

capillaries is fenestrated, likethat in other endocrineorgans. The cells containgranules of stored hormonethat are extruded from thecells by exocyrosis.

The granules presumably breakdown in the peri-capillaryspace, and their contentsenter the capillaries.



Posterior Pituitary

• Posterior pituitary is madeup of endings of the axonsthat arise from cell bodies inthe supraoptic andparaventricular nuclei andpass to the posterior

pituittary via thehypothalamohypophysialtrat. Most of the supraopticfiber end in the posteriorlobe itself whereas some ofthe paraventricular fibersend in the median eminence.

• There are also pituicytes,stellate cells which aremodified astrocyres.



Posterior Pituitary

Hormones secreted byposterior pituitary aresynthesized in nerve cellbodies in hypothalamus andsecreted by axonal terminalsin posterior pituitary, and

from there into veins, whichcarry them into systemiccirculation

Hormones secreted byposterior pituitary are :

1. ADH (vasopressin)

2. Oxytocin

Both are peptide hormones.



Hypothalamic Control over Endocrine Organs



Hypothalamic Control over Endocrine Organs

Characteristics of hypothalamic releasing hormones

1. Secretion in pulses

2. Act on specific membrane receptors

3. Transduce signals via second messengers

4. Stimulate release of stored pituitary hormones

5. Stimulate synthesis of pituitary hormones

6. Stimulates hyperplasia and hypertophy of target

cells

7. Regulates its own receptor



Pituitary

Hypothalamic releasinghormone

Effect on pituitary

Corticotropin releasing hormone

(CRH)

Stimulates ACTH secretion

Thyrotropin releasing hormone

(TRH)

Stimulates TSH and Prolactin

secretionGrowth hormone releasing

hormone (GHRH)

Stimulates GH secretion

Somatostatin Inhibits GH (and other

hormone) secretion

Gonadotropin releasing

hormone (GnRH) a.k.a LHRH

Stimulates LH and FSH

secretion

Prolactin releasing hormone

(PRH)

Stimulates PRL secretion

Prolactin inhibiting hormone

(dopamine)

Inhibits PRL secretion



Classification of hormones

• There are two classifications of hormones:

steroidal and non-steroidal

• Steroidal hormones are lipid soluble and

can diffuse directly into the target cells via

the cell membrane.

• Non-Steroidal hormones are synthesized

by amino acids and target cells need

receptors to diffuse into the cell.



Classification of hormones

• Peptide hormones (Hydrophilic: polar) – formed from chains of amino acids

– most hormones are peptide hormones

– longer chains are called protein hormones

– Example: growth hormone• Steroid hormones (Hydrophobic: nonpolar)

– type of lipid derived from cholesterol

– Example: testosterone

• Biogenic amines (Hydrophobic: nonpolar) – small molecules produced by altering the structure of

a specific amino acid

– Example: thyroid hormone



Water and Lipid soluble hormones



Major mechanism of hormone action

• Negative feedback Loop

• Positive feedback Loop



Negative Feedback Loop

• Mechanism:

– A stimulus starts a process

– Process causes release of a hormone

– Either the hormone or a product of its effects

causes the process to slow down or turn off.

• Example: the regulation of the bloodglucose level in the body



Negative Feedback Loop



Positive Feedback Loop

• Called positive because it accelerates theoriginal process

– can ensure that the pathway continues to run

– can speed up its activities.

• Few positive feedback loops in the human

endocrine system. – Example: milk release from the mammary

glands



Positive Feedback Loop



Thyroid gland

• Largest pure endocrine gland

• Internally, composed of hollow follicles- separated by areolar CT rich in capillaries

- walls are formed of cuboidal or squamous epithelialcells (follicular cells)

- lying within the epithelium are parafollicular (C) cells

- central lumen filled with colloid (‘gluelike’) consisting of

thyroglobulin (protein precursor to thyroid hormone)

• Amino-based TH and protein based Calcitonin



Thyroid gland



Anatomy and Histological Organization of the Thyroid Gland



The Regulation of Thyroid Secretion

• Thyroid function is regulatedprimarily by variations in thecirculating level of TSH.

• TSH secretion is increasedby TRH and inhibited in anegative feedback fashion

by circulating free T4 andT3.

• The effect of T4 is enhancedby production of T3 in thecytoplasm of the pituitarycells by the 5'-D2 they

contain.

• TSH secretion is alsoinhibited by stress, and inexperimental animals it isincreased by cold anddecreased by warmth.



• Some of thewidespread effectsof THs in the bodyare secondary tostimulation of O2

consumption(calorigenic action).

• THs also affectgrowth anddevelopment in

mammals, helpregulate lipidmetabolism, andincrease theabsorption ofcarbohydrates fromthe intestine.

• They also increasethe dissociation ofO2 fromhemoglobin byincreasing red cell2,3-DPG



Parathyroid glands

• Lie on the posterior surface of the thyroid gland surrounded byCT capsules (number varies)

• Contains thick branching cords composed of 2 types of endocrinecells

- chief cells – small abundant parathyroid glandular cells that

produce PTH- Oxyphil cells and transitional cells – likely immature of inactive

principal cells

• Regulates calcium homeostasis: PTH increases calcium levelsand is essential to life:

1) stimulates osteoclasts to release calcium from bones

2) decreases secretion of calcium by the kidney

3) activates vit D, which stimulates uptake of Ca by the intestine



Parathyroid glands



Ad l l d



Adrenal gland



Adrenal gland

Divided into 2 regions:

- Suprarenal cortex

Zona Glomerulosa – mineralocorticoids

Zona Fasciculata – glucocorticoids

Zona Reticularis – androgens

- Suprarenal medulla

Chromaffin cells produce epinephrine andnorephinephrine

- modified ganglionic sympathetic neurons

- active in the ‘fight, flight, and fright’ (fight or flight) response

- hormones stored in secretory vesicles



Adrenal gland



Adrenal gland

• Both basal secretion of glucocorticoidsand the increased secretion provokedby stress are dependent upon ACTHfrom the anterior pituitary.

• Angiotensin II also stimulates theadrenal cortex, but its effect is mainlyon aldosterone secretion.

• Large doses of a number of othernaturally occurring substances,

including vasopressin, serotonin, andVIP, are capable of stimulating theadrenal directly, but there is noevidence that these agents play anyrole in the physiologic regulation ofglucocorticoid secretion.



Mechanism of action of ACTH When ACTH binds to its

receptor (R), adenylylcyclase (AC) is activatedvia Gs. The resultingincrease in cAMP activatesprotein kinase A, and thekinase phosphorylatescholesteryl ester hydrolase(CEH), increasing its

activity.

Consequently, more freecholesterol is formed andconverted topregnenolone. Note that inthe subsequent steps insteroid biosynthesis,

products are shuttledbetween the mitochondriaand the smoothendoplasmic reticulum(SER). Corticosterone isalso synthesized andsecreted.



Effects of Glucocorticoids

Glucocorticoids:

• increase protein catabolism,hepatic glycogenesis andgluconeogenesis.

• exert an antiinsulin action inperipheral tissues

• raise plasma lipid levels andincrease ketone body formationbut in healthy persons theincrease in insulin secretionprovoked by the rise in plasmaglucose obscures these actions




Small amounts of glucocorticoids must be

present for a number of metabolic reactionsto occur, although the glucocorticoids donot produce the reactions by themselves.This effect is called their permissive action.Permissive effects include the requirementfor glucocorticoids to be present:

• for glucagon and catecholamines to exerttheir calorigenic effects;

• for catecholamines to exert their lipolyticeffects; and

• for catecholamines to produce pressorresponses and bronchodilation.




Glucocorticoid excess:

• exert a significant mineralocorticoidaction Hypertension

• leads to bone dissolution by decreasingbone formation and increasing boneresorption osteoporosis

• accelerate the basic

electroencephalographic rhythms andproduce mental aberrations rangingfrom increased appetite, insomnia, andeuphoria to frank toxic psychoses

Eff t f Gl ti id




Pharmacological doses of corticoids:

• inhibit the inflammatory response totissue injury

• inhibit ACTH secretion to the pointthat severe adrenal insufficiency

• inhibit growth, decrease GHsecretion, induce PNMT, anddecrease TSH secretion

• accelerate the maturation ofsurfactant in the lungs (during fetallife)



Renin Angiotensin System

• Renin, an acid protease secreted by the kidneys into thebloodstream, acts in concert with angiotensin-convertingenzyme (ACE) to form angiotensin II. It splits the decapeptideangiotensin I from the amino terminal end ofangiotensinogen.

• Angiotensinogen is synthesized in the liver. Its circulatinglevel is increased by glucocorticoids, thyroid hormones,estrogens, several cytokines, and angiotensin II.

• ACE is a dipeptidyl carboxypeptidase that splits off thephysiologically inactive angiotensin I, forming theoctapeptide angiotensin II




• Most of the converting enzyme that forms angiotensin IIin the circulation is located in endothelial cells. Much ofthe conversion occurs as the blood passes through thelungs, but conversion also occurs in many other parts ofthe body.

• Angiotensin II produces arteriolar constriction and a risein systolic and diastolic blood pressure. It is one of themost potent vasoconstrictors known, being 4 to 8 timesas active as norepinephrine

• Angiotensin II also acts directly on the adrenal cortex toincrease the secretion of aldosterone, and the renin –angiotensin system is a major regulator of aldosteronesecretion



R i A i t i S t




Pancreas



Pancreas

• It is a soft,lobulated organthat stretchesobliquely acrossthe posteriorabdominal wallin the epigastricregion.

• It is situatedbehind the

stomach andextends from theduodenum to thespleen.



Pancreas

The pancreas isretroperitoneal except for asmall part of its

tail.

It consists of ahead, uncinateprocess, neck,body, and tail.

Pancreas



Pancreas

The pancreatic branches of splenic artery also supply the neck, body and tail of the pancreas.The largest of those branches is called arteria pancreatica magna.

A dorsal dorsal or superior pancreatic artery has a dorsal origin in relation to the pancreas; itis usually present, but has a great variability of origin: from the splenic artery (37%), fourthbranch of the celiac (33%), superior mesenteric (21%), and less often from the hepatic(8%). It helps to form an inferior or transverse pancreatic artery, which supplies the lower

portion of the body

The superior

pancreaticoduodenal

artery from

gastroduodenal artery and

the inferior

pancreaticoduodenal

artery from superior

mesenteric artery

bifurcates into anterior and

posterior branches, join

each other and form

anterior and posterior

pancreaticoduodenal

arcades supplying the

pancreatic head and

uncinate process

P



• Veins accompany the SPDA and IPDA. The body and neck of thepancreas drain into splenic vein; the head drains into the superiormesenteric and portal veins.

• Lymph is drained via the splenic, celiac and superior mesentericlymph

Pancreas



Pancreas

Pancreas contains endocrine and exocrinecells:

• Exocrine acinar cells, form most of the gland- secrete a powerful, digestive fluid digestive juice

with enzymes into the duodenum; its duct joins the

common bile duct

• Endocrine cells are contained in sphericalbodies- pancreatic islets or islets of Langerhans

- about 1 million scattered among the exocrine cells



Pancreas

Each islet contains 4 major cells

• Alpha cells – glucagon

• Beta cells – insulin• Delta cells – somatostatin (growth-hormone

inhibiting hormone)

• F cells – pancreatic polypeptide (PP)



Hormones of Pancreas

Pancreas



Pancreas

• Glucagon raises bloodglucose levels.

• Insulin lowers bloodglucose levels.

• Somatostatin inhibits bothglocagon and insulinrelease.

• Pancreatic polypeptide

inhibits somatostatinsecretion, gallbladdercontraction and secretionof digestive enzymes bythe pancreas.

Glucagon



Glucagon

• Hypoglycemia

stimulatesrelease ofglucagon

• Glucagon

causeshepatocytes toconvertglycogen toglucose(glycogenolysis)

• Hyperglycemiainhibit releaseof glucagon



Insulin

• Insulin allows glucoseto diffuse into cells,increases amino aciduptake by cells, andincreaes fatty aciduptake by cells.

• This facilitatesglucose conversioninto glycogen(glycogenesis),synthesis of proteins,and synthesis of fattyacids (lipogenesis).



Insulin: Mechanism of Action

• Binding of insulin triggers the tyrosine

kinase activity of the β subunits,producing autophosphorylation of theβ subunits on tyrosine residues. Theautophosphorylation, which isnecessary for insulin to exert itsbiologic effects, triggers

phosphorylation of some cytoplasmicproteins and dephosphorylation ofothers, mostly on serine and threonineresidues.

• Four related insulin receptor substrate(IRS) proteins in cells have beendescribed (IRS - I to IV). IRS-1 hasreceived the most attention, butpathways in addition to IRS-l playimportant roles in the actions ofinsulin. Exposure to increased amounts of

insulin leads to down regulation.




Effects of Insulin

The physiologic effects of

insulin are far-reachingand complex.

ff f



Effects of Insulin

Rapid (seconds)

Increased transport ofglucose, AA and K into

insulin-sensitive cells

Delayed (hours)

Increase in mRNA forlipogenic and otherenzimes

Intermediate (minutes)

• Stimulation of proteinsynthesis

• Inhibition of proteindegradation

• Activation of glycolyticenzimes and glycogensynthase

• Inhibition of phosphorilaseand gluconeogenicenzimes



Effects of Insulin

• Glucose enters cells by facilitated diffusion or, in the intestineand kidneys, by secondary active transport with Na+.

• In muscle, fat and some other tissues, insulin facilitates glucoseentry into cells by increasing the number of glucose transporters inthe cell membranes.

• They differ from and have no homology with the sodium-dependentglucose transporters, SGLT 1 and SGLT 2, responsible for thesecondary active transport of glucose out of the intestine and renaltubules, although the SGLTs also have 12 transmembrane domains.

• Seven different glucose transporters have been characterized. Theycontain 492-524 amino acid residues, and their affinity for glucosevaries. Each transporter appears to have evolved for special tasks.

Eff t f I li



Effects of Insulin



Effects of Insulin

• GLUT 4 is the transporter inmuscle and adipose tissuethat is stimulated by insulin. Apool of GLUT 4 molecules ismaintained in vesicles in thecytoplasm of insulin-sensitivecells.

• When the insulin receptors ofthese cells are activated, thevesicles move rapidly to thecell membrane and fuse withit, inserting the transportersinto the cell membrane.

• When insulin action ceases,the transporter-containingpatches of membrane areendocytosed, and thevesicles are ready for the nextexposure to insulin.

Activation of the insulin receptor brings about the

movement of the vesicles to the cell membrane by

activating phosphoinositol-3 kinase.

Insulin also increases the entry of glucose into livercells, but it does not exert this effect by increasing

the number of GLUT 4 transporters. Instead, it

induces glucokinase, and this increases the

phosphorylation of glucose, so that the intracellular

free glucose concentration stays low,

facilitating the entry of glucose into the cell.



Pancreas

Interactions between

Glucagon and Insulin

Starvation



Gonads



Gonads

• Ovaries (female gonads). – Produce steroid hormones.

• Estrogens.

• Progesterone.

– Produce inhibin. – Produce relaxin.

• Testes (male gonads). – Produce testosterone (an androgen).

– Produce inhibin.

G d



Gonads

• Testes:- Interstitial cells produce androgens (testosterone)

promotes production of functional sperm, maintains

secretory glands, influences 2nd sexual characteristics,

and stimulates muscle growth

- Nurse cells (or sustentabular cells) secrete inhibin

• Ovaries

- Follicular cells produce estrogens and inhibin- Corpus luteum releases progestins and relaxin

Gonads



Gonads

Female sex hormones

• Estrogen and progesterone along with FSH and LH (from theanterior pituitary), regulate the menstrual cycle, maintainpregnancy, and prepare the mammary glands for lactation.

• Maintain the feminine secondary sex characteristics (largerbreasts and hips).

• Inhibin inhibits secretion of FSH.

• Relaxin increases the flexibility of the pubic symphisis duringpregnancy and helps dilate the cervix during labor and delivery.

Male sex hormones

• Testosterone regulates the production of sperm. maintainssecretory glands, and stimulates muscle growth.

• Stimulates the production of male secondary sexcharacteristics (beard growth and deepening of the voice).



Pi l



Pineal

• Contains neurons, glial cells, and special secretorycells called pinealocytes

• Secretes melatonin

• Production rates rises at night (darkness) anddeclines during the day

• Melatonin contributes to the body’s biological clock.

• Melatonin slows the maturation of sperm, oocytes,and reproductive organs

Clinical Note - Endocrine Abnormalities



ClinicalImplications ofEndocrineSystem



“Pour être subversif, il faut être subjectif ”

(Frédéric Beigbeder)

endocrine system 5 morphophysiology

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