Endocrine GlandsEndocrine Glands33rdrd Year Medicine Year Medicine

Dr. Zienab Al-RefaieDr. Zienab Al-Refaie

Associate. Prof. PhysiologyAssociate. Prof. Physiology

Endocrine GlandsEndocrine Glands

Endocrine GlandsEndocrine GlandsIntroductionIntroduction

ObjectivesObjectives::

1- intercellular communication1- intercellular communication

2-classification of hormones.2-classification of hormones.

3-neuro endocrine inter-relation.3-neuro endocrine inter-relation.

4-control of hormone secretion.4-control of hormone secretion.

5-characters of hormone receptors.5-characters of hormone receptors.

6-mechanisms of hormone action.6-mechanisms of hormone action.

Intercellular communication: cell to Intercellular communication: cell to cell relation and its method cell relation and its method

1- Direct communication :1- Direct communication : it occurs between it occurs between contiguous cells of the same type . e.g. myocardial cells contiguous cells of the same type . e.g. myocardial cells

2- Paracrine communication :2- Paracrine communication :the chemical the chemical messengers secreted by some cells may affect the messengers secreted by some cells may affect the nearby cells. nearby cells.

3- Endocrine communication: 3- Endocrine communication: some body cells release some body cells release specific chemical substances, hormones, in blood to specific chemical substances, hormones, in blood to affect distant body cells . This method is slow because affect distant body cells . This method is slow because the blood velocity is slow (0.001-1m/sec).the blood velocity is slow (0.001-1m/sec).

4- Neural communication:4- Neural communication: the cells of the nervous the cells of the nervous system communicate at their synaptic junctions with system communicate at their synaptic junctions with each other and with other body cells by releasing each other and with other body cells by releasing neurotransmitters. neurotransmitters.

Nervous &Endocrine Systems Nervous &Endocrine Systems inter-relationinter-relation

The nervous and the endocrine systems The nervous and the endocrine systems are inter-related in the hypothalamus are inter-related in the hypothalamus through the:through the:

The The hypothalamo-hypophyseal tracthypothalamo-hypophyseal tract . . TheThe hypothalamo hypothalamo--hypopheseal –portal hypopheseal –portal

circulationcirculation . .

Hypothalamo-hypophyseal Portal Hypothalamo-hypophyseal Portal circulationcirculation

NoteNote

The anterior pituitary receives The anterior pituitary receives portal bloodportal blood

The posterior pituitary receives The posterior pituitary receives arterial blood.arterial blood.

Hypothalamo-hypophyseal Tract Hypothalamo-hypophyseal Tract

Differences between steroid and Differences between steroid and peptide hormonespeptide hormones

PropertyPropertySteroidSteroidPeptidePeptide

Interaction with Interaction with the cell the cell membrane.membrane.

DiffusesDiffusesInteracts with Interacts with membrane membrane receptorsreceptors

ReceptorsReceptorsIn cytoplasm or In cytoplasm or nucleusnucleus

In cell In cell membranemembrane

Action Action Gene Gene transcriptiontranscription

Second Second messengermessenger

Response timeResponse timeHours to daysHours to daysSeconds to Seconds to minutesminutes

Forms of H. in the BloodForms of H. in the Blood

1- Free. 1- Free. * It is not carried on a plasma protein . * It is not carried on a plasma protein . * It can bind directly to the receptors : active . * It can bind directly to the receptors : active . * It is small in size , so can be filtered in urine . * It is small in size , so can be filtered in urine .

2- protein bound . 2- protein bound . * Carried on plasma protein . * Carried on plasma protein . * It acts as a reservoir. * It acts as a reservoir. * It increases the half life of the hormone.* It increases the half life of the hormone. * It is more soluble in plasma ( the lipid steroids , when bound to * It is more soluble in plasma ( the lipid steroids , when bound to plasma proteins they are transformed into water soluble. plasma proteins they are transformed into water soluble. * It is large in size , and so is not filtered in urine . * It is large in size , and so is not filtered in urine .

Control of hormone secretionControl of hormone secretion

I- Nervous control : through the I- Nervous control : through the

hypothalamus.hypothalamus.

2- Freed back control :2- Freed back control :

* -Ve feed back.* -Ve feed back.

* +Ve feed back.* +Ve feed back.

What is Feed BackWhat is Feed Back

When the endocrine gland senses When the endocrine gland senses that there is too much (or too little) of that there is too much (or too little) of the regulated variable, it responds by the regulated variable, it responds by decreasing (or increasing) the rate of decreasing (or increasing) the rate of hormone secretion. hormone secretion.

-Ve Feed back control of Hormone -Ve Feed back control of Hormone secretionsecretion

+Ve feed back+Ve feed back

During ovarian cycle in femalesDuring ovarian cycle in females

High Estrogen Increase FSH More Estrogen

Increase LHOvulation

QuizQuiz H. that binds to cytoplasmic receptors and H. that binds to cytoplasmic receptors and

circulates mostly bound to plasma ptn.circulates mostly bound to plasma ptn. Peptide H. that lacks hypothalamic Peptide H. that lacks hypothalamic

pituitary control.pituitary control. H. that shows late onset of action and acts H. that shows late onset of action and acts

through nuclear receptors.through nuclear receptors. Peptide H. which is formed in the post. Peptide H. which is formed in the post.

Pituitary.Pituitary.

A- thyroxin B- insulinA- thyroxin B- insulinC- cortisole D- vasopressinC- cortisole D- vasopressin

Hormone ReceptorsHormone Receptors

* Site* Site * Specificity* Specificity * Dynamic: * Dynamic: Down-regulationDown-regulation Up-regulationUp-regulation

Adenyl Cyclase PathwayAdenyl Cyclase Pathway

Some hormones that act by adenyl Some hormones that act by adenyl cyclase pathwaycyclase pathway

ACTH Angiotensin IIACTH Angiotensin II

Calcitonin ParathormoneCalcitonin Parathormone

Catecholamines (Catecholamines (ββ) )

LH FSHLH FSH

CRH ADH ( kidney)CRH ADH ( kidney)

Glucagon TSHGlucagon TSH

Phospholipase C PathwayPhospholipase C Pathway

Some hormones that act by Some hormones that act by phospholipase pathwayphospholipase pathway

Angiotensin II OxytocinAngiotensin II Oxytocin

ADH (smooth muscles)ADH (smooth muscles)

Catecholamines (Catecholamines (αα receprors) receprors)

GnRHGnRH

GHRHGHRH

Second MessengerSecond Messenger

Peptide hormone is the 1Peptide hormone is the 1stst messenger (outside the cell).messenger (outside the cell).

When it binds with its receptor, it When it binds with its receptor, it leads to formation of a 2leads to formation of a 2ndnd messenger (inside the cell).messenger (inside the cell).

The 2The 2ndnd messenger performs the messenger performs the effects of the hormone.effects of the hormone.

Mechanism of Action of Steroid H.Mechanism of Action of Steroid H.

Effects of Ant. Pituitary H.Effects of Ant. Pituitary H.

Actions of Ant. Pituitary H. Actions of Ant. Pituitary H.

Actions and Control of GHActions and Control of GH

Effect of sleep & exercise on GH Effect of sleep & exercise on GH secretionsecretion

Effect of GH injection on growth Effect of GH injection on growth raterate

Diabetogenic effects of GHDiabetogenic effects of GH

Target EffectTarget Effect

Muscle Decreased glucose uptakeMuscle Decreased glucose uptake

Fat Increased lipolysis.Fat Increased lipolysis.

Liver Increased gluconeogenesisLiver Increased gluconeogenesis

All of them Insulin resistanceAll of them Insulin resistance

GH and IGFGH and IGF

Effect of arginine infusion on GH Effect of arginine infusion on GH and Insulinand Insulin

Effect of protein deficiency and Effect of protein deficiency and nutrient replacement on GH levelnutrient replacement on GH level

AcromegalyAcromegaly

Increased levels of GHIncreased levels of GH

Gigantism: increased before pubertyGigantism: increased before puberty

before union of epiphysisbefore union of epiphysis

growth of all bones and visceragrowth of all bones and viscera

Acromegaly: increased after pubertyAcromegaly: increased after puberty

after union of epiphysisafter union of epiphysis

growth of flat bonesgrowth of flat bones

Major role of ProlactinMajor role of Prolactin

Antidiuretic hormoneAntidiuretic hormone

It is secreted from:It is secreted from:

* Supraoptic nucleus: mainly, to the * Supraoptic nucleus: mainly, to the

posterior pituitary then into the blood.posterior pituitary then into the blood.

* Paraventricular nuclei: to lesser extent ,* Paraventricular nuclei: to lesser extent ,

to the anterior pituitary, stimulates ACTHto the anterior pituitary, stimulates ACTH

Actions of ADHActions of ADHOn the V2 receptors of the late distal and the cortical On the V2 receptors of the late distal and the cortical

collecting tubules, induces translocation of water collecting tubules, induces translocation of water channels, aquaporin 2 to the cell membrane. This channels, aquaporin 2 to the cell membrane. This allows passage of water from the lumen to the allows passage of water from the lumen to the inside of the cell & then to the renal interstitium.inside of the cell & then to the renal interstitium.

On the V1 receptors in vascular smooth muscles, On the V1 receptors in vascular smooth muscles, increases intracellular Caincreases intracellular Ca2+2+ , which induces , which induces vasoconstriction in cases of hemorrhage.vasoconstriction in cases of hemorrhage.

On the V3 receptors of the corticotropes, stimulates On the V3 receptors of the corticotropes, stimulates secretion of ACTH that in its turn causes cortisole secretion of ACTH that in its turn causes cortisole secretion in stressful conditions. secretion in stressful conditions.

Action of ADH on V2 receptorsAction of ADH on V2 receptors

Relationship between change in Relationship between change in plasma osmolality and ADHplasma osmolality and ADH

Relationship between plasma Relationship between plasma volume and ADHvolume and ADH

Analysis of various types of Analysis of various types of diabetes insipidusdiabetes insipidus

ADH level and Plasma osmolality in ADH level and Plasma osmolality in both types of diabetes insipidusboth types of diabetes insipidus

The adrenal cortexThe adrenal cortex

It is the outer part of the adrenal gland and forms about It is the outer part of the adrenal gland and forms about 80 % of the gland. 80 % of the gland.

It secretes steroid hormones . It is divided into three It secretes steroid hormones . It is divided into three distinct zones:distinct zones:

Zona Glomerulose, Zona Glomerulose, the outermost layer,the outermost layer, secretes secretes mineralocorticoids, aldosterone, desoxycorticosterone mineralocorticoids, aldosterone, desoxycorticosterone and corticosterone . They maintain Naand corticosterone . They maintain Na++ and K and K ++ balance balance and ECF volume and ECF volume

Zona Fasciculata :Zona Fasciculata : is the middle widest zone and is the middle widest zone and secretes glucocorticoids : cortisol and corticosterone that secretes glucocorticoids : cortisol and corticosterone that have widespread effects on carbohydrate and protein have widespread effects on carbohydrate and protein metabolism . metabolism .

Zona Reticularis : Zona Reticularis : is the innermost layer and secretes is the innermost layer and secretes mainly sex hormones, dehydroepiandrosterone ( DHEA ), mainly sex hormones, dehydroepiandrosterone ( DHEA ), androstenedione and small amounts of estrogen androstenedione and small amounts of estrogen . .

Actions of cortisoleActions of cortisoleOn carbohydrate metabolism : On carbohydrate metabolism : 1- Stimulation of gluconeogenesis by the liver from 1- Stimulation of gluconeogenesis by the liver from

amino acids. amino acids. 2- Increased gluconeogenesis leads to the build up of 2- Increased gluconeogenesis leads to the build up of

sufficient glycogen sufficient glycogen On protein metabolism:On protein metabolism: 1- Cortisol reduces protein synthesis &increases protein 1- Cortisol reduces protein synthesis &increases protein

catabolism in all body cells except liver cells.catabolism in all body cells except liver cells. 2- It increases plasma amino acid level.2- It increases plasma amino acid level. 3- It inhibits amino acid transport to extrahepatic cells 3- It inhibits amino acid transport to extrahepatic cells

and stimulates amino acid transport into liver cells.and stimulates amino acid transport into liver cells.On fat metabolism:On fat metabolism: 1-Cortisol has a lipolytic action.1-Cortisol has a lipolytic action. 2-It increases FFA in plasma. 2-It increases FFA in plasma.

Actions of cortisoleActions of cortisoleEffect on vascular system:Effect on vascular system: Cortisole is required for the maintenance of normal Cortisole is required for the maintenance of normal

arterial blood pressure in response to the vasoconstrictor arterial blood pressure in response to the vasoconstrictor effect of catecholamines (effect of catecholamines (permissive actionpermissive action).).

Effect on Kidney:Effect on Kidney: Cortisole is essential for rapid excretion of a water load, Cortisole is essential for rapid excretion of a water load,

as it inhibits ADH secretion and action.as it inhibits ADH secretion and action.Functions of cortisole in stress:Functions of cortisole in stress: Cortisole is required for catecholamines to exert their Cortisole is required for catecholamines to exert their

pressor and lipolytic actions.pressor and lipolytic actions. It increases FFA that are important as emergency It increases FFA that are important as emergency

energy source, and raises blood glucose level together energy source, and raises blood glucose level together with catecholamines to protect against hypoglycemia. with catecholamines to protect against hypoglycemia.

Actions of cortisoleActions of cortisoleEffect of cortisole on blood cells and immunity:Effect of cortisole on blood cells and immunity: Cortisole decreases the number of circulating eosinphils and the Cortisole decreases the number of circulating eosinphils and the

number of lymphocytes (T lymphocytes) mainly.number of lymphocytes (T lymphocytes) mainly. It increases number of neutrophils (but inhibits their function). It increases number of neutrophils (but inhibits their function). It inhibits production of interleukin 2 (IL-2) by lymphocytes.It inhibits production of interleukin 2 (IL-2) by lymphocytes. It antagonizes the synthesis, secretion and actions of interleukin 1. It antagonizes the synthesis, secretion and actions of interleukin 1. High conctrations of glucocorticoids interfere with antibody High conctrations of glucocorticoids interfere with antibody

production from B-lymphocytes.production from B-lymphocytes.N.B.N.B. * Large doses of glucocorticoids can lead to fulminating infection.* Large doses of glucocorticoids can lead to fulminating infection. * On the other hand, this ability of glucocorticoids to suppress * On the other hand, this ability of glucocorticoids to suppress

immunity makes them useful in prevention of immunological immunity makes them useful in prevention of immunological rejection of transplanted organs.rejection of transplanted organs.

Anti – Inflammatory Effects of Cortisole:Anti – Inflammatory Effects of Cortisole: Cortisol stabilizes the membranes of lysosomes so prevents the Cortisol stabilizes the membranes of lysosomes so prevents the

release of their proteolytic enzymes.release of their proteolytic enzymes. It diminishes vasodilation.It diminishes vasodilation. It decreases migration of white blood cells into the inflammed area.It decreases migration of white blood cells into the inflammed area.

Relative potency of cortisole and Relative potency of cortisole and some synthetic steroidssome synthetic steroids

Pattern of cortisole level during the Pattern of cortisole level during the dayday

Pattern of cortisole and ACTH level Pattern of cortisole and ACTH level during the dayduring the day

Effect of stress on cortisole Effect of stress on cortisole secretionsecretion

Control of cortisole secretionControl of cortisole secretion

Chronotropic variations in the level Chronotropic variations in the level of some hormonesof some hormones

Manifestations of hypercortisismManifestations of hypercortisism

Cushing’s diseaseCushing’s disease

A patient with Cushing’s disease before and after subtotal adrenalectomy

Actions of aldosteroneActions of aldosterone

Aldosterone increases the reabsorption of NaAldosterone increases the reabsorption of Na++ from urine, sweat, saliva, gastric juice and from urine, sweat, saliva, gastric juice and colon.colon.

It stimulates secretion of K It stimulates secretion of K ++ by the kidney by the kidney Because HBecause H22O is passively reabsorbed with O is passively reabsorbed with

Na Na ++, there is no increase in plasma Na , there is no increase in plasma Na ++ concentration. so ECFV expands in an concentration. so ECFV expands in an isotonic manner.isotonic manner.

Aldosterone also causes H Aldosterone also causes H ++ to be secreted to be secreted

into renal tubules.into renal tubules.

Control of aldosterone levelControl of aldosterone level

Renin- angiotensin systemRenin- angiotensin system Atrial natriuretic peptideAtrial natriuretic peptide Plasma k+ level Plasma k+ level Role of ACTH Role of ACTH Plasma Na+ level Plasma Na+ level

Addison’s diseaseAddison’s disease

Actions and control of aldosteroneActions and control of aldosterone

Best of luckBest of luck