hormons

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HORMONES

Endocrine cells secrete hormones; neurons

secrete neurotransmitters.

In each case, the extracellular messenger

passes to another cell where it binds to a

specific receptor molecule and triggers a

change in the activity of the second cell.

Hormones are carried rapidly in the blood

between distant organs and tissues

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A specific chemical compound

Produced by a specific tissue of the body

Where it is released in the body fluids And carried to a distant target tissue

Where it affects a pre-existing mechanism

And is effective is small amounts.

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Coordination of systems involve

Nervous System

Rapid response

Short lasting Uses neurotransmitters

Endocrine System

Slow response

Long lasting

Uses hormones

Homeostasis

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Proteins and Polypeptides Oxytocin

Insulin

Biogenic amines Thyroxine

Catecholamines

Steroids Estrogens

Progestins

Androgens

Eicosanoids Prostaglandins

Thromboxanes

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Major Endocrine Organs are

Hypothalamus

Pituitary gland

Thyroid gland

Parathyroid gland

Thymus

Adrenal gland

Pancreas

Ovaries

Testes

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Vascularity of endocrine tissue

Autocrine glands - local to same cells that

released the hormone

Paracrine glands - local to adjacent cells

Endocrine-Hormone - release into interstitial

space, lymphatics, and blood. Pheromone - into the air

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Synthesis of hormons from Tyr

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Synthesis of Steroid Hormons

f h h h h

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Most of these hormones act through a

few fundamentally similar

mechanisms. We first consider one of the best-understood hormone

mechanisms involving cAMP as the second messenger-which mediates the cellular response to epinephrine.

We then describe examples of several other fundamentalhormone mechanisms, involving different secondmessengers (cGMP, diacylglycerols, an inositoltrisphosphate, Ca2+),

The phosphorylation and dephosphorylation of specific

proteins are shown to be central to these mechanisms. Finally, we describe how steroid hormones function

through the regulation of gene activity.

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Mechanisms of Hormones Action

There are two mechanisms:

Membrano cytozolic or nondirect, that

influence with helping of messengers;

Cytosolic niuclear or direct

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Prin intermediul nicleotidelor cicliceRspuns

Rspuns

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RH

Gs ProteinAdenyl

Cyclase

Active c AMP dependant

Protein Kinase

Inactive c AMP dependant

Protein Kinase

Protein + ATP ADP + Protein PO4

Cells

Response

ICF

ECF

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Phosphodiestherase (E) descomposes AMPcyclic:

AMPc -------------- AMP

+ H2O Activity of E increases iones of calciu,

prostaglandine, insuline.

steroides ,Thyroides hormones and

methylxantineses ( cofeine , theophyline )decrease activity of E and support life of AMP- cyclic.

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Diacylglycerol and Inozytol 3

phosphate

1. 1. H+RHR

2. 2. HRGp

3. Gp PhospholipazeiC

4. Phospholipaze C activates to membranePhospholipids and produce DAG and Iinozitol triPhosphate

DAG activate PK C

Inozitol 3 fosfate increase endoplasmaticconcentration of Ca

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RH

G ProteinPhospholipase C

Active

Protein Kinase C

Inactive

Protein Kinase C

Protein PO4 Protein

Cells Response

PIP2 DAG + IP3

Cells Response

ICF

ECF

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Diacilglicerolul i inozitol fosfaii

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Mecanismul citozolic de aciune

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Action of Steroid Hormones

Steroid hormones (estrogen, progesterone, andcortisol, for example), too hydrophobic to dissolvereadily in the blood, are carried on specific carrierproteins from the point of their release to their target

tissues. In the target tissue, these hormones pass through the

plasma membrane by simple diffusion and bind tospecific receptor proteins in the nucleus

The hormone-receptor complexes act by binding to

highly specific DNA sequences called hormoneresponse elements (HREs) and altering geneexpression.

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Action of Steroid Hormones

Hormone binding triggers changes in the

conformation of the receptor proteins so that

they become capable of interacting with

specific transcription factors

The bound hormone-receptor complex can

either enhance or suppress the expression

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Classification of Hormones

Classification of Hormones

Hormones are classified according to:

histological principle - according to the place

of their synthesis;

chemical structure;

biological function; mechanism of action on the target cell.

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Histological principle of hormones

classification:

hypothalamic hormones - releasing factors:

a) liberins b) statins

Hypothalamic via posterior pituitary:

Oxytocin

Antidiuretic hormone (ADH)

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classification:

Anterior pituitary hormones tropins:

Follicle-stimulating hormone (FSH)

Luteinizing hormone (LH)

Prolactin (LTH) Thyroid stimulating hormone (TSH) thyrotropin

Adrenocorticotropic hormone (ACTH)

Growth hormone (GH) somatotropinMelanocyte-stimulating hormone (MSH)melanotropin

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classification: Thyroid gland hormones:

Thyroxin and Triodothyroxin

Calcitonin

Parathyroid gland hormones

Parathyroid hormone

Adrenal cortex hormones

Mineralocorticoids (aldosterone)

Glucocorticoids (cortisol)

Adrenal medulla hormones

Catecholamines (Adrenalin and Noradrenalin)

Pancreas hormones

Glucagons

Insulin

Ovary hormones

Estrogens (estradiol)

Progestrogen

Placenta hormones

Chorionic gonadotropin

Testes hormones

Andro ens testosterone

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Hormone hierarchy

Hormone systems are often linked to each

another, giving rise in some cases to a

hierarchy of higher-order and lower-order

hormones.

A particularly important example is the

pituitaryhypothalamic axis, which is

controlled by the central nervous system(CNS)

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Hormone hierarchy

Nerve cells in the hypothalamus react tostimulatory or inhibitory signals from the CNS byreleasing activating or inhibiting factors, whichare known as liberins (releasing hormones) andstatins (inhibiting hormones).

These neurohormones reach theadenohypophysis by short routes through the

bloodstream. In the adenohypophysis, theystimulate (liberins) or inhibit (statins) thebiosynthesis and release oftropines.

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Hormone hierarchy

Tropines (glandotropic hormones) in turnstimulate peripheral glands to synthesizeglandular hormones.

Finally, the glandular hormone acts on its targetcells in the organism.

In addition, it passes effects back to the higher-order hormone systems. This (usually negative)

feedback influences the concentrations of thehigher-order hormones, creating a feedbackloop.

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Hormonii hipotalamo-hipofizari Secreia hormonilor adenohipofizei este reglat de ctre peptide

elaborate n diverse arii ale hipotalamusului releasing factori(neurohormoni)

Liberine i statine

Hormonii Hormonii tropi

hipotalamici hipofizari

1. somatoliberina + somatotropina

2. corticoliberina + corticotropina

3. tireoliberina + tireotropina

4. folililiberina + folitropina

5. luliliberina + lutropina6. prolactoliberina + prolactina

7. prolactostatina -

8. somatostatin

9. melanostatina -

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Hypothalamic Releasing Factors

Release stimulating factor

Release inhibitory factor

Each Pituitary Hormone has a set orstimulating and inhibiting factors except theGonadotropins.

Prolactin Release Factor = GonadotropinInhibitory factor.

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Releasing factors Release hormones

Release inhibiting hormones

Oxytocin Milk ejection mechanism Uterine Contraction

Induction of labor

Orgasmic responses

Feedback mechanism - Positive

Vasopressin or ADH - AntiDiuretic Hormone Action on Distal Convoluted tubule and Collecting Duct

Pressor effects

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MSH - Intermediate lobe Anterior Lobe Hormones

Basophilic and Acidophilic

Trophic and nontrophic hormones

Growth Hormone Prolactin

Thyroid Stimulating Hormone - TSH

AdrenoCorticoTrophic Hormone - ACTH

Follicle Stimulating Hormone

Lutenizing Hormone Long Loop and Short Loop Feedback Systems

Autocrine Feedback Systems

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Protein mole. wgt. 22,000

Bound to High Affinity Bound protein and LowAffinity Bound protein.

Binding compensates for irrating secretion rates.

Half life varies 6 to 20 minutes.

Somatomedins - produced by liver - polypeptides- growth factors

Growth hormone increase IGF-I somatomedin What is growth?

Uptake of Amino Acids

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Protein Anabolic

Increased plasma phosphorus

Increase absorption of calcium in

gut Diabetogenic

Growth Periods

Dwarfism

Giantism

Acromegly

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Hands

Feet

Jaws

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Prolactin Release Inhibitory Factor

Prolactin Release Stimulating Factor

Gonadotrophin Release Inhibiting Factor Prolactin hormone - Pregnancy hormone

199 amino acids

20 minute half life

Receptor resembles growth hormone receptor

Increases milk production

Maintains corpus luteum

Dopamine controls rate of release

Calcium Homeostasis and Endocrine

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Calcium Homeostasis and Endocrine

Regulation of Ca++ concentration

Calcium is required for muscle contraction, intracellularmessenger systems, cardiac repolarization.

The total quantity of calcium in organism is about 1 kg:

99% of calcium is located in bones as hydroxyapatites

1% of calcium is located in cells and blood

In the blood calcium can be in the following state:

In complex with albumin (40% total blood calcium)

In complex with anions - Phosphate and Citrate (10% total blood

calcium) In a free form ionic calcium Ca++(50%)

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Calcium Homeostasis

The most important hormones for maintaining

calcium levels in the body are:

Parathyroid hormone (PTH) produced by

Parathyroid gland

Calcitriol - 1,25(OH)2D3 (the active form of

vitamin D)

Calcitonineproduced byParafollicular C cells ofThyroid gland

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Parathyroid hormone

The major regulator is Parathyroid hormone, which is partof a negative feedback loop to maintain [Ca++]. PTHsecretion is stimulated by hypocalcemia, and it worksthrough three mechanisms to increase Ca++ levels:

PTH stimulates the release of Ca++ from bone, stimulating

bone resorption. PTH decreases urinary loss of Ca++ by stimulating Ca++

reabsorption. PTH also inhibits phosphate reabsorption.

PTH indirectly stimulates Ca++ absorption in the smallintestine by stimulating synthesis of 1,25(OH)

2D

3in the

kidney.

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C l it i

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Calcitonine

Produced by Parafollicular C cells of Thyroid inresponse to increased Ca++

Actions

Inhibit osteoclastic resorption of bone Decrease renal Ca++ excretion and increase renal

PO43- excretion

Non-essential hormone. Patients with totalthyroidectomy maintain normal Ca++concentrations

Calcitriol

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Calcitriol

Sources Food Vitamin D2

UV light mediated cholesterol metabolism vitaminD3

Metabolism

D2 and D3 are converted to 25(OH)-D in the liver

25(OH)-D is converted to 1,25(OH)2-D in the Kidney

Function Stimulation of Osteoblasts

Increases absorption in intestin of dietary Ca++

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Calcitonine

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Calcitonine

Produced by Parafollicular C cells of Thyroid inresponse to increased Ca++

Actions

Inhibit osteoclastic resorption of bone Decrease renal Ca++ excretion and increase renal

PO43- excretion

Non-essential hormone. Patients with totalthyroidectomy maintain normal Ca++concentrations

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Hormones of the pancreas

The endocrine portion of pancreas is representedby clusters of cells called islets of Langerhans.The islets contain four types of cells. In order of

abundance, they are: beta cells, which secrete insulin and amylin

alpha cells, which secrete glucagon;

delta cells, which secrete somatostatin, and

gamma cells, which secrete pancreaticpolypeptide.

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Insulin

Insulin is a small protein consisting of

an alpha chain (A chain) of 21 amino acidslinked by two disulfide (SS) bridges to a

beta chain (B chain) of 30 amino acids. Beta cells secrete insulin in response to a

rising level of circulating glucose ("blood

sugar"). Insulin major function is to maintain low

blood glucose level.

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Insulin

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Synthesis of insulin

Preproinsulin, the first precursor.The signal peptide at the N-end is deleted, creatingproinsulin .

Proinsulin differs from insulin in that it has a third

peptide, C, which connects the A and B peptidestogether. The primary sequence of proinsulin goes inthe order "B-C-A". This C peptide is spliced from thechain by the action of proteolytic enzymes, known asprohormone convertases.

The remaining polypeptides (51 amino acids in total),the B- and A- chains, are bound together by disulphidebonds.

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Regulation of insulin secretion:

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Regulation of insulin secretion:

The secretion of insulin is increased by: The secretion of insulin is decreased by:

glucose or carbohydrates intake amino acids from ingested

proteins (especially alanine,

glycine and arginine)

acetylcholine, released from vagus

nerve endings (parasympathetic

nervous system)

cholecystokinin, released by

intestinal mucosa

gastrin and secretin

glucose-dependent insulinotropic

peptide (GIP).

Low glucose level in the blood Adrenalin and noradrenalin

(sympathetic nervous system)

Somatostatin from D-cells of

pancreas

Mechanism of insulin action

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Mechanism of insulin action.

Insulin triggers these effects by binding to the insulinreceptor a transmembrane proteinembedded in theplasma membrane of the responding cells.

The insulin receptor is a tyrosine kinase. The activatedreceptor phosphorylates a number of intracellular proteins

(insulin receptor substrateor IRS), which in turn alters theiractivity, thereby generating a biological response.

Activation of insulin receptor leads to internal cellularmechanisms that directly affect glucose uptake byregulating the number and operation of protein molecules

in the cell membrane that transport glucose into the cell -glucose transporters - GLUT.
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellMembranes.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellMembranes.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellMembranes.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellMembranes.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellMembranes.html

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Mechanism of insulin action

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Mechanism of insulin action.

The actions of insulin on the global human metabolismlevel include:

Activation of RNA transcription and proteinssynthesis;

Control of cellular intake and activation of thetransmembrane transport of glucose, amino acids,ions;

Modification of the activity of numerous enzymes:

- activation of enzyme, that catalyze the synthesis ofglycogen, fat, proteins.

- inactivation of enzyme, that catalyze the reactions ofcatabolism.

Glucose metabolism differs depending

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Glucose metabolism differs depending

on the type of cell

Muscle and Adipose tussue require the use of glucosetransporters GLUT-4, which is only made available in thepresence of insulin.

Once insulin binds to the receptors the glucosetransporters penetrate through the plasma membrane. At

this point, glucose can be transported into the cell at arapid rate.

Insulin stimulates skeletal muscle fibersto take up glucose and convert it into glycogen;

use glucose as an energy substrate

take up amino acids from the blood and convert them intoprotein.
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Effects of insulin on Liver Tissue

. Insulin acts on liver cells

stimulating them to take up glucose from the

blood and convert it into glycogen,

inhibiting glycogenolysis and gluconeogenesis, activating glycolysis in order to produce

intermediates for glycerol and fatty acid synthesis,

activating fat synthesis

Additional Functions of Insulin:
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Additional Functions of Insulin:

In addition to its role in carbohydrate and lipidmetabolism, insulin serves the following functions:

Increases amino acid transport into cells- when insulinlevels are low, proteins are degraded

Regulates transcription, changing the amount ofmRNA present in the cell

Activates cell growth, DNA synthesis and cellreplication

Increases the permeability of most cells to potassium,magnesium and phosphate ions

Increases the secretion of hydrochloric acid by Parietalcells in the stomach.

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Diabetes mellitus

Diabetes mellitus is an insulin deficiency state. Diabetes mellitus is an endocrine disorder characterized by

many signs and symptoms.

Primary among these are:

Hyperglycemia Glucoseuria - a failure of the kidney to reclaim glucose so

that glucose spills over into the urine

Polyuria - a resulting increase in the volume of urinebecause of the osmotic effect of this glucose (it reduces the

return of water to the blood). polydipsia - increased thirst and consequent increased fluid

intake
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Type 1 Diabetes Mellitus

Type 1 Diabetes Mellitus (also known as Insulin-Dependent DiabetesMellitus or IDDM)

is characterized by little (hypo) or no circulating insulin;

most commonly appears in childhood.

It results from destruction of the beta cells of the islets.

The destruction results from a cell-mediated autoimmune attack againstthe beta cells.

Type 1 diabetes is controlled by carefully-regulated injections of insulin.

Acute complications including hypoglycemia, diabetic ketoacidosis, ornonketotic hyperosmolar comamay occur if the disease is not adequatelycontrolled. Serious long-termcomplications include cardiovasculardisease, chronic renal failure, retinal damage, which can lead toblindness, several types ofnerve damage, microvascular damage and poorwound healing. Poor healing ofwounds, particularly of the feet, can leadto gangrene, possibly requiring amputation.
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Type 2 Diabetes Mellitus

Type 2 diabetes mellitus usually strikes in adults and,particularly often, in overweight people. Despite researchefforts, the precise nature of the defects leading to type IIdiabetes have been difficult to ascertain, and thepathogenesis of this condition is plainly multifactorial.

Insulin injections are not useful for therapy. Rather the disease is controlled through dietary therapy

and hypoglycemic agents. Several drugs, all of which can betaken by mouth, are useful in restoring better control overblood sugar in patients with type 2 diabetes. However, late

in the course of disease, patients may have to begin to takeinsulin. It is as though after years of pumping out insulin inan effort to overcome the patient's insulin resistance, thebeta cells become exhausted.

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Glucagon

is synthesized and secreted from alpha cells(-cells) ofthe islets of Langerhans, which are located in theendocrine portion of the pancreas.

Glucagon is a linear polypeptide of 29 amino acids. It issynthesized as proglucagon and proteolyticallyprocessed to yield glucagon within alpha cells of thepancreatic islets.

Glucagon has a major role in maintaining normalconcentrations of glucose in blood, and is often

described as having the opposite effect of insulin. Thatis, glucagon has the effect of increasing blood glucoselevels.

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Effects of Glucagon

Glucagon acts principally on the liver where it

stimulates the conversion of:

glycogen into glucose (glycogenolysis) and

fat and protein into intermediate metabolites

that are ultimately converted into glucose

(gluconeogenesis)

Hormones of thyroid gland.

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Hormones of thyroid gland.

Follicular cells in the gland producethe 2 main thyroid hormones, tetraiodothyronine(thyroxine, T4), and triiodothyronine (T3).

These hormones act on cells in every body tissueby combining with nuclear receptors and alteringexpression of a wide range of gene products.

Thyroid hormone is required for normal brain

and somatic tissue development in the fetus andneonate, and, in all ages, regulates protein,carbohydrate, and fat metabolism.

Synthesis and Release of Thyroid

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Hormones

The follicular cells surround a space filled with colloid,which contain thyroglobulin - a glycoprotein containingtyrosine. Thyroglobulin is synthesized by thyroidepithelial cells and secreted into the lumen of thefollicle colloid.

Synthesis of thyroid hormones requires iodine. Iodine,ingested in food and water as iodide, is actively takenup from blood by thyroid epithelial cells, which have ontheir outer plasma membrane a sodium-iodide

symporter or "iodine trap". Once inside the cell, iodideis transported into the lumen of the follicle along withthyroglobulin.

http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/thyroid/nai_symport.htmlhttp://www.vivo.colostate.edu/hbooks/pathphys/endocrine/thyroid/nai_symport.htmlhttp://www.vivo.colostate.edu/hbooks/pathphys/endocrine/thyroid/nai_symport.htmlhttp://www.vivo.colostate.edu/hbooks/pathphys/endocrine/thyroid/nai_symport.htmlhttp://www.vivo.colostate.edu/hbooks/pathphys/endocrine/thyroid/nai_symport.htmlhttp://www.vivo.colostate.edu/hbooks/pathphys/endocrine/thyroid/nai_symport.htmlhttp://www.vivo.colostate.edu/hbooks/pathphys/endocrine/thyroid/nai_symport.html

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Hormones

Sinthesis of thyroid hormones is catalyzed by the enzymethyroid peroxidase.

Thyroid peroxidase catalyzes two sequential reactions:

Iodination of tyrosines on thyroglobulin (also known as"organification of iodide").

Synthesis of thyroxine or triiodothyronine from twoiodotyrosines.

Tyrosine in contact with the membrane of the follicularcells is iodinated at 1 (monoiodotyrosine) or 2

(diiodotyrosine) sites and then coupled to produce the 2forms of thyroid hormone (diiodotyrosine + diiodotyrosine T4; diiodotyrosine + monoiodotyrosine T3):

h id id

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Thyroid peroxidase

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Once inside the thyroid follicular cells, T3 andT4 are cleaved from thyroglobulin: colloid-laden endosomes fuse with lysosomes, whichcontain hydrolytic enzymes that digestthyroglobulin, thereby liberating free thyroidhormones.

Free T3 and T4 are then released into the

bloodstream, where they are bound to serumproteins for transport to target cells.

Mechanism of Action of ThyroidH

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Hormones

The mechanism of action of thyroid hormones iscytosolic-nuclear mechanism.

Receptors for thyroid hormones are intracellular DNA-binding proteins that function as hormone-responsivetranscription factors, very similar conceptually to thereceptors for steroid hormones.

Thyroid hormones enter cells through membranetransporter proteins.

Once inside the nucleus, the hormone binds its

receptor, and the hormone-receptor complex interactswith specific sequences of DNA in the promoters ofresponsive genes.

Eff f Th id H
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Effects of Thyroid Hormones

Metabolism: Thyroid hormones stimulate diverse metabolic activities inmost tissues, leading to an increase in basal metabolic rate.

One consequence of this activity is to increase body heat production,which seems to result, at least in part, from increased oxygenconsumption and rates of ATP hydrolysis. A few examples of specificmetabolic effects of thyroid hormones include:

Lipid metabolism: Increased thyroid hormone levels stimulate fatmobilization, leading to increased concentrations of fatty acids in plasma.

Carbohydrate metabolism: Thyroid hormones stimulate almost all aspectsof carbohydrate metabolism, including enhancement of insulin-dependententry of glucose into cells and increased gluconeogenesis andglycogenolysis to generate free glucose.

Growth: Thyroid hormones are clearly necessary for normal growth inchildren and young animals, as evidenced by the growth-retardationobserved in thyroid deficiency.

Other Effects

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Other ffects

Cardiovascular system: Thyroid hormones increases heartrate, cardiac contractility and cardiac output. They alsopromote vasodilatation, which leads to enhanced bloodflow to many organs.

Central nervous system: Both decreased and increased

concentrations of thyroid hormones lead to alterations inmental state. Too little thyroid hormone tends to feelmentally sluggish, while too much induces anxiety andnervousness.

Reproductive system: Normal reproductive behavior and

physiology is dependent on having essentially normal levelsof thyroid hormone. Hypothyroidism in particular iscommonly associated with infertility.

H th idi

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Hypothyroidism

Hypothyroidism is the result from any condition that results in thyroid hormonedeficiency. Two well-known examples include:

Iodine deficiency: Iodide is absolutely necessary for production of thyroidhormones; without adequate iodine intake, thyroid hormones cannot besynthesized. In the case of iodide deficiency, the thyroid becomes inordinatelylarge and is called a goiter.

Primary thyroid disease: Inflammatory diseases of the thyroid that destroy parts

of the gland are clearly an important cause of hypothyroidism. Common symptoms of hypothyroidism arising after early childhood include

lethargy, fatigue, cold-intolerance, weakness, hair loss and reproductive failure. Ifthese signs are severe, the clinical condition is called myxedema.

The most severe and devastating form of hypothyroidism is seen in young childrenwith congenital thyroid deficiency. If that condition is not corrected bysupplemental therapy soon after birth, the child will suffer from cretinism, a form

of irreversible growth and mental retardation. Most cases of hypothyroidism are readily treated by oral administration of

synthetic thyroid hormone.
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Infancy onset

Persists throughout life

Severe mental retardation

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Hyperthyroidism

Hyperthyroidism results from secretion of thyroid hormones. Inhumans the most common form of hyperthyroidism is Gravesdisease, an immune disease in which autoantibodies bind to andactivate the thyroid-stimulating hormone receptor, leading tocontinual stimulation of thyroid hormone synthesis. Anotherinteresting, but rare cause of hyperthyroidism is so-called

hamburger thyrotoxicosis. Common signs of hyperthyroidism are basically the opposite of

those seen in hypothyroidism, and include nervousness, insomnia,high heart rate, eye disease and anxiety. Graves disease iscommonly treated with anti-thyroid drugs, which suppresssynthesis of thyroid hormones primarily by interfering with

iodination of thyroglobulin by thyroid peroxidase.

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Hyperthyroidism

Adrenal Gland

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The two adrenal glands are located immediatelyanterior to the kidneys, encased in a connective

tissue capsule and usually partially buried in an

island of fat. Like the kidneys, the adrenal glandslie beneath the peritoneum.

Sectioned mammalian adrenal gland reveals two

distinct regions:

An inner medulla

An outer cortex

The inner medulla, which is a source of

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,the catecholamines epinephrine andnorepinephrine. The chromaffin cell isthe principle cell type.The adrenal

medulla consists ofmasses of neuronsthat are part of the sympathetic branchof the autonomic nervous system.Instead of releasing theirneurotransmitters at a synapse, theseneurons release them into the blood.

Thus, although part of the nervoussystem, the adrenal medulla functionsas an endocrine gland.

The outer cortex, which secretes severalclasses of steroid hormones(glucocorticoids, mineralocorticoids and

androgens). Cortex consists of threeconcentric zones of cells that differ inthe major steroid hormones theysecrete.

Adrenal Medulla Hormones
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Cells in the adrenal medulla synthesize andsecrete epinephrine and norepinephrine. Theratio of these two catecholamines differs: inhumans 80% of the catecholamine output isepinephrine.

Following release into blood, these hormonesbind adrenergic receptors on target cells,

where they induce essentially the same effectsas direct sympathetic nervous stimulation.

Synthesis and Secretion ofCatecholamines

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Catecholamines

Secretion of these hormones is stimulated byacetylcholine release from preganglionic sympathetic

fibers innervating the medulla. Many types of "stresses"

stimulate such secretion, including exercise,

hypoglycemia and trauma. Following secretion into

blood, the catecholamines are carried in the circulation

by albumin.

Biosinteza

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Biosinteza

Adrenergic Receptors and Mechanismof Action

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of Action Adrenergic receptors are typical examples of seven-pass

transmembrane proteins that are coupled to G proteins whichstimulate or inhibit intracellular signaling pathways

(membrane-intracellular mechanism).

Complex physiologic responses result from adrenal medulla

stimulation because there are multiple receptor types which

are differentially expressed in different tissues and cells. The

alpha and beta adrenergic receptors were defined:

Receptor Effectively Binds Effect of Ligand Binding

Alpha1 Epinephrine, Norepinphrine Increased free calcium

Alpha2 Epinephrine, Norepinphrine Decreased cyclic AMP

Beta1 Epinephrine, Norepinphrine Increased cyclic AMP

Beta2 Epinephrine Increased cyclic AMP

Effects of Medulla Hormones

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Release ofadrenaline and noradrenaline is triggeredby nervous stimulation in response to physical ormental stress.

Common stimuli for secretion of adrenomedullary

hormones include exercise, hypoglycemia, hemorrhageand emotional distress.

Circulating epinephrine and norepinephrine releasedfrom the adrenal medulla have the same effects on

target organs as direct stimulation by sympatheticnerves, although their effect is longer lasting.

A major effects mediated byepinephrine and norepinephrine are:

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epinephrine and norepinephrine are:

Hyperglycemia

Stimulation of glycogenbreakdown in skeletal muscle to provideglucose for energy production

Stimulation of lipolysis in fat cells: this provides fatty acids forenergy production in many tissues and aids in conservation ofreserves of blood glucose.

Increased metabolic rate: oxygen consumption and heatproduction increase throughout the body in response toepinephrine.

Increased rate and force of contraction of the heart muscle: this ispredominantly an effect of epinephrine acting through beta

receptors. Constriction of blood vessels: norepinephrine, in particular, causes

widespread vasoconstriction, resulting in increased resistance andhence arterial

A major effects mediated by

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epinephrine and norepinephrine are:

Dilation of bronchioles: assists in pulmonary ventilation. Dilation of the pupils: particularly important in situations

where you are surrounded by velociraptors underconditions of low ambient light.

Inhibition of certain "non-essential" processes: an example

is inhibition of gastrointestinal secretion and motor activity. clotting time of the blood is reduced;

increased ACTH secretion from the anterior lobe of thepituitary.

All of these effects prepare the body to take immediateand vigorous action.

Adrenal Steroids
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Class of Steroid

Region of adrenal

glandMajor Representative Effects

Mineralocorticoids

Glomerulosa

AldosteroneNa+, K+ and water

homeostasis

Glucocorticoids

Fasciculata

ReticularisCortisol

Glucose homeostasis and

many others

Androgens

Fasciculata

Reticularis Testosterone

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Steroid hormones are hydrophobic and mustbe carried in the blood bound to a serum

protein:

Glucocorticoids are transported by transcortincorticosteroid-binding globulin;

Mineralocorticoids are transported by plasma

albumin.

The cytosolic-nuclear mechanism of

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steroid hormones action

. Like all steroid hormones, cortisol andaldosterone bind to their respective receptor

(a protein present in the cytoplasm and/or

nucleus of "target" cells), and the resultinghormone-receptor complex binds to a

hormone response elementin DNA to

modulate transcription of responsive genes.

Mineralocorticoids

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The major target of aldosterone is the

distal tubule of the kidney, where it

stimulates exchange of sodium and

potassium. Three primary physiologic

effects of aldosterone result:

Increased resorption of sodium(Na+).

Increased resorption of water. This is

an osmotic effect directly related to

increased resorption of sodium. This

helps maintain normal blood

pressure. Increased renal excretion of

potassium (K+).

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Control of Aldosterone Secretion

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Small increases in blood levels of potassiumstrongly stimulate aldosterone secretion.

Angiotensin II: Activation of the renin-angiotensin

system as a result of decreased renal blood flow(usually due to decreased vascular volume)

results in release of angiotensin II, which

stimulates aldosterone secretion.

a drop in the level of sodium ions in the blood;

ACTH (adrenocorticotropic hormone)

Glucocorticoids
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The glucocorticoids get their name fromtheir effect of raising the level of blood

glucose. One way they do this is by

stimulating gluconeogenesis in the liver:

the conversion of fat and protein into

intermediate metabolites, that areultimately converted into glucose.

Cortisol and the other glucocorticoids

also have a potent anti-inflammatory

effect on the body. They depress the

immune response, especially cell-

mediated immune responses.

Effects on Metabolism
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Glucocorticoids stimulate processes that serve to increase andmaintain normal concentrations of glucose in blood. These effectsinclude:

Stimulation of gluconeogenesis, particularly in the liver: Thispathway results in the synthesis of glucose from non-hexosesubstrates such as amino acids and lipids.

Mobilization of amino acids from extrahepatic tissues: These serveas substrates for gluconeogenesis.

Inhibition of glucose uptake in muscle and adipose tissue: Amechanism to conserve glucose.

Stimulation of fat breakdown in adipose tissue: The fatty acids

released by lipolysis are used for production of energy in tissues likemuscle, and the released glycerol provide another substrate forgluconeogenesis.

Effects on Inflammation and ImmuneFunction

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Function

Glucocorticoids have potent anti-inflammatory and immunosuppressive

properties.

As a consequence, glucocorticoids are widelyused as drugs to treat inflammatory

conditions such as arthritis or dermatitis, and

as adjunction therapy for conditions such asautoimmune diseases.

Control of Cortisol Secretion

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Cortisol and other glucocorticoids are

secreted in response to a single stimulator:adrenocorticotropic hormone (ACTH).

ACTH is itself secreted under control ofthe hypothalamic peptide corticotropin-releasing hormone (CRH).

Virtually any type of physical or mental

stress results in elevation of cortisolconcentrations in blood due to enhancedsecretion of CRH in the hypothalamus.

Cortisol secretion is suppressed byclassical negative feedback loops.

The combination of positive and negativecontrol on CRH secretion results inpulsatile secretion of cortisol. Typically,pulse amplitude and frequency are highestin the morning and lowest at night.

Hyperadrenocorticism
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Hyperadrenocorticism or Cushings disease. Excessivelevels of glucocorticoids are seen in two situations

Excessive endogenous production of cortisol

Administration of glucocorticoids for theraputic

purposes. Cushing's disease has widespread effects on

metabolism and organ function. A diverse set of clinicalmanifestations accompany this disorder, including

hypertension, apparent obesity, muscle wasting, thinskin, and metabolic aberrations such as diabetes.

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Hyper-

Adrenalism

Primarily theGlucocorticoids

Hypoadrenocorticism

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Hypoadrenocorticism

Insufficient production of cortisol, often accompanied by analdosterone deficiency, is called hypoadrenocorticism orAddison's disease

Most commonly, this disease is a result ofinfectiousdisease (e.g. tuberculosis in humans) or autoimmune

destruction of the adrenal cortex. As with Cushing's disease, numerous diverse clinical signs

accompany Addison's disease, including cardiovasculardisease, lethargy, diarrhea, and weakness.

Aldosterone deficiency can be acutely life threatening due

to disorders of electrolyte balance and cardiac function.
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Low adrenal activity

Gonocorticoid appearnormal

Increased

pigmentation due toincreased ACTH

Sex Hormones

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Sex Hormones

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Classic Sex Hormones: Gonad and

Adrenal

Estrogen

Progesterone

Dihydrotestosterone

Testosterone

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Follicles

Estrogen

Progesterone

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Mature Testis

Semeniferous Tubules, Interstitial cells

Testosterone

Estrogen

Inhibin

hormons

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