GROUP WEB PAGE

GROUP WEB PAGE

Group members are as follows: -

Neelam Dass

Yogita Kapdapia

Gayuatri Murgai

Muhammad Ruhani (B.sc. Biomedical Science)

Ruby Sidhu

Samra Zubairi

DESCRIPTION:
For our Internet topic we chose to do hormones. Hormones are chemicals that transfer information and instructions between cells in animals and plants. Hormones are also described as the body's chemical messengers. Hormones are responsible in regulating growth and development. Hormones control the function of various tissues. Hormones support reproductive functions and regulate metabolism. Most hormones are produced by the glands of the endocrine system, which are the pituitary; thyroid; adrenal glands and the ovaries or testes. The endocrine glands produce and secrete hormone directly into the bloodstream. Not all hormones are produced by the endocrine glands. Mucous membranes of the small intestine secrete hormones that stimulate secretion of the digestive juices from the pancreas. Other hormones are produced in the placenta an organ formed during pregnancy. The placenta regulates some aspects of foetal development.
==========================================================================================================

The Adrenal Gland: Introduction and Index by.M.i.Al-Ruhani

When you think about the adrenal glands, you should think about stress. Stress can take many forms: taking an examination, recovering from a broken bone, running away from an invading army, or maintaining proper levels of energy substrates in the face of even mild starvation. For human there is even considerable stress associated with shopping.

The adrenal glands are orange-coloured endocrine glands, which are located on the top of both kidneys. The adrenal glands are triangular shaped and measure about one-half inch in height and 3 inches in length. Each gland consists of a medulla the centre of the gland, which is surrounded by the cortex. The medulla is responsible for producing epinephrine and norepinephrine (adrenaline). The adrenal cortex produces other hormones necessary for fluid and electrolyte (salt) balance in the body such as cortisone and aldosterone. The adrenal cortex also makes sex hormones but this only becomes important if overproduction is present.

The adrenal gland produces three major classes of hormones, each of which aid in dealing with the multitude of small and large stresses faced by animals and people almost daily. There is no doubt that at least two of these groups' -glucocorticoids and mineralocorticoids - are necessary for life.

Core information on adrenal physiology is presented in the following topics:

* Functional anatomy of the adrenal gland

*Adrenal medullar hormones - Epinephrine and Norepinephrine

*Adrenal Steroids

*Mineralocorticoids

*Glucocorticoids

**Advanced and supplemental information on adrenal physiology: **

** Histology of the adrenal gland

==========================================================================================================

Functional Anatomy of the Adrenal Gland

==========================================================================================================

The two adrenal glands are located immediately anterior to the kidneys, encased in a connective tissue capsule and usually partially buried in an island of fat. Like the kidneys, the adrenal glands lie beneath the peritoneum (i.e. they are retroperitoneal). The exact location relative to the kidney and the shape of the adrenal gland varies among species.

Inspection of a mammalian adrenal gland that has been sectioned reveals two distinct regions, as demonstrated below with a sheep adrenal:

An inner medulla, which is a source of the catecholamines epinephrine and norepinephrine. The chromaffin cell is the principle cell type. The medulla is richly innervated by preganglionic sympathetic fibres and is, in essence, an extension of the sympathetic nervous system.

An outer cortex, which secretes several classes of steroid hormones (glucocorticoids and mineralocorticoids, plus a few others). Histologic examination of the cortex reveals three concentric zones of cells that differ in the major steroid hormones they secrete.

Despite their organisation into a single gland, the medulla and cortex are functionally different endocrine organs, and have different embryological origins. The medulla derives from ectoderm (neural crest), while the cortex develops from mesoderm. The utility, if any, of having them together in one discrete organ is not obvious. In some species, amphibians and certain fish, for example, two separate organs are found.

==========================================================================================================

Adrenal Medullar Hormones

==========================================================================================================

Cells in the adrenal medulla synthesise and secrete norepinephrine and epinephrine. The ratio of these two catecholamines differs considerably among species: in humans, cats and chickens, roughly 80, 60 and 30% of the catecholamine output is epinephrine. Following release into blood, these hormones bind adrenergic receptors on target cells, where they induce essentially the same effects as direct sympathetic nervous stimulation.

Synthesis and Secretion of Catecholamines Synthesis of catecholamines begins with the amino acid tyrosine, which is taken up by chromaffin cells in the medulla and converted to norepinephrine and epinephrine through the following steps:

Norepinephine and epinephrine are stored in electron-dense granules, which also contain ATP and several neuropeptides. Secretion of these hormones is stimulated by acetylcholine release from preganglionic sympathetic fibre's innervating the medulla. Many types of "stresses" stimulate such secretion, including exercise, hypoglycaemia and trauma. Following secretion into blood, the catecholamines bind loosely to and are carried in the circulation by albumin and perhaps other serum proteins.

Adrenergic Receptors and Mechanism of Action

The physiologic effects of epinephrine and norepinephrine are initiated by their binding to adrenergic receptors on the surface of target cells. These receptors are prototypical examples of seven-pass transmembrane proteins that are coupled to G proteins, which stimulate or inhibit intracellular signalling pathways.

Complex physiologic responses result from adrenal medullary stimulation because there are multiple receptor types, which are differentially expressed in different tissues and cells. The alpha and beta-adrenergic receptors and their subtypes were originally defined by differential binding of various agonists and antagnonists and, more recently, by analysis of molecular clones.

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

Physiologic Effects of Medullary Hormones

In general, circulating epinephrine and norepinephrine released from the adrenal medulla have the same effects on target organs as direct stimulation by sympatheticnerves, although their effect is longer lasting. Additionally, of course, circulating hormones can cause effects in cells and tissues that are not directly innervated. The physiologic consequences of medullary catecholamine release are justifiably framed as responses, which aid in dealing with stress. These effects can be predicted to some degree by imagining what would be needed if, for example, you were trapped in Jurassic Park when the power went off. A listing of some major effects mediated by epinephrine and norepinephrine are:

Increased rate and force of contraction of the heart muscle:

This is predominantly an effect of epinephrine acting through beta-receptors.

Constriction of blood vessels:

Norepinephrine, in particular, causes widespread vasoconstriction, resulting in increased resistance and hence arterial blood pressure.

Dilation of bronchioles:

Assists in pulmonary ventilation.

Stimulation of lipolysis in fat cells:

This provides fatty acids for energy production in many tissues and aids in conservation of dwindling reserves of blood glucose.

Increased metabolic rate:

Oxygen consumption and heat production increase throughout the body in response to epinephrine. Medullary hormones also promote breakdown of glycogen in skeletal muscle to provide glucose for energy production.

Dilation of the pupils:

Particularly important in situations where you are surrounded by velociraptors under conditions of low ambient light.

Inhibition of certain "non-essential" processes:

An example is inhibition of gastrointestinal secretion and motor activity.

Common stimuli for secretion of adrenomedullary hormones include exercise, hypoglycaemia, haemorrhage and emotional distress.

====================================================================

Adrenal Steroids

======================================================================================

The adrenal cortex is a factory for steroid hormones. In toto, at least two to three dozen different steroids are synthesised and secreted from this tissue, but two classes are of particular importance:

Class of Steroid	Major Representative	Physiologic Effects
Mineralocorticoids	Aldosterone	Na+, K+ and water homeostasis
Glucocorticoids	Aldosterone	Glucose homeostasis and many others

Additionally, the adrenal cortex produces some sex steroids, particularly androgens, and a talent of considerable importance in such diseases as congenital adrenal hyperplasia.

Like all steroids, adrenal "corticosteroids" are synthesised from cholesterol through a series of enzyme-mediated transformations. The details of these pathways are presented elsewhere, but the major branches are easy to understand.

Each of the three major pathways involves sequential processing by a group of enzymes, some of which reside in endoplasmic reticulum and others inside mitochondria. Hence, synthesis involves shuttling of the steroids between these two organelles.

Synthesis of the different steroids is not uniformly distributed through the cortex. For example, the outermost group of cells (zona glomerulosa) synthesises aldosterone, but essentially no cortisol or androgens because those cells do not express the enzyme 17-alpha-hydroxylase which is necessary for synthesis of 17-hydroxypregnenolone and 17-hydroxyprogesterone. That enzyme is however present in cells of the inner zones of the cortex (zonae fasiculata and reticularis), which are the major sites of cortisol production.

Like all steroid hormones, cortisol and aldosterone bind to their respective receptors, and the resulting hormone-receptor complexes bind to a hormone response element to modulate transcription of responsive genes. Although the physiologic effects of these two steroid hormones are distinctly different, their receptors are quite similar and, most interestingly, they bind to the same consensus response element in DNA!

==========================================================================================================

Mineralocorticoids

==========================================================================================================

Removal of the adrenal glands leads to death within just a few days. Observation of such an unfortunate subject would reveal several key derangements:

* The concentration of potassium in extracelluar fluid becomes dramatically elevated

*Urinary excretion of sodium is high and concentrations of sodium in extracellular fluid decreases significantly

*Volume of extracellular fluid and blood plummet

*The heart begins to function poorly, cardiac output declines and shock ensues

These phenomena are a direct result of loss of mineralocorticoid activity, and can largely be prevented by replacement of salts and mineralocorticoids. Clearly mineralocorticoids are acutely critical for maintenance of life!

Aldosterone and Mineralocorticoid Receptors

The principal steroid with mineralocorticoid activity is aldosterone. Cortisol, the major glucocorticoid in non-rodent species, is said to have "weak mineralocorticoid activity", which is of some importance because cortisol is secreted very much more abundantlythan aldosterone. Another way to state this is that a small fraction of the mineralocorticoid response in the body is due to cortisol rather than aldosterone.

The mineralocorticoid receptor binds both aldosterone and cortisol with equal affinity.

Moreover, the same DNA sequence serves as a hormone response element for the activated (steroid-bound) forms of both mineralocorticoid and glucocorticoid receptors. An obvious question is:

How in the world can aldosterone stimulate specific biological effects in this kind of system, particularly when blood concentrations of cortisol are something like 2000-fold higher than aldosterone?

A large part of the answer is that, in aldosterone-responsive cells, cortisol is effectively destroyed, allowing aldosterone to bind its receptor without competition. Target cells or aldosterone express the enzyme 11-beta-hydroxysteroid dehydrogenase, which has no effect on aldosterone, but converts cortisol to cortisone, which has only a very weak affinity for the mineralocorticoid receptor. In essence, this enzyme "protects" the cell from cortisol and allows aldosterone to act appropriately. Some tissues (e.g. hippocampus) express abundant mineralocorticoid receptors but not 11-beta HSD - they therefore do not show responses to aldosterone because aldosterone is not present in quantities sufficient to compete with cortisol.

An interesting demonstration of this enzyme protection system is seen in chronic licorice intoxication.

Physiologic Effects of Mineralocorticoids

Mineralocorticoids play a critical role in regulating concentrations of minerals- particularly sodium and potassium - in extracellular fluids. As described above, loss of these hormones leads rapidly to life-threatening abnormalities in electrolyte and fluid alliance.

The major target of aldosterone is the distal tubule of the kidney, where it stimulates exchange of sodium and potassium. Three primary physiologic effects result:

*Increased resorption of sodium: sodium loss in urine is decreased under aldosterone stimulation.

*Increased resorption of water, with consequent expansion of extracellular fluid volume. This is an osmotic effect directly related to increased resorption of sodium.

* Increased renal excretion of potassium.

Knowing these effects should quickly suggest the cellular mechanism of action this hormone. Aldosterone stimulates transcription of the gene encoding the sodium-potassium ATPase, leading to increase numbers of "sodium pumps" in the basolateral membranes of tubular epithelial cells. Aldosterone also stimulates expression of a sodium channel, which facilitates uptake of sodium from the tubular lumen.

Aldosterone has effects on sweat glands, salivary glands and the colon, which are essentially identical to those seen in the distal tubule of the kidney. The major net effect is again to observe body sodium by stimulating its resorption or, in the case of the colon, absorption from the intestinal lumen. Conservation of water follows conservation of sodium.

==========================================================================================================

FIVE WEB-PAGE EVALUATION

1.ADRENAL GLANDS MARGARET MERCY HOSPITAL SCHOOL OF MEDICAL TECHNOLOGY March 23rd, 1995 Adrenal glands are paired organs located one at the upper pole of each kidney. Each gland consists of outer cortex and inner medulla. ADRENAL CORTEX: composed of 3 layers 1-Zona glomerul

http://members.aol.com/neskander/cortisol.html

Evaluation: An articles from members aol.com.on adrenal gland has Provides good links to authors and associates and further sites that the reader can pursue for further information. Also very good linkage with sickle cell anemia.

2.Adrenal Gland Cancer: symptoms, diagnosis and treatments. Doctors for patients write EndocrineWeb. Endocrine Disorders & Endocrine Surgery Cancer of the Adrenal Glands. ~ ADRENAL CANCER ~ Adrenocortical carcinoma is a rare tumor afflicting only one or two percent in million.

http://endocrineweb.com/adreca.html

Evaluation: Doctor writes Well-argued articles by Endocrine web for patients. Endocrine Disorders & Endocrine Surgery Cancer of the Adrenal Glands Email link for further information. Copyright © 1997, 1998. Endocrine Web Inc. All rights reserved

3.Adrenal Tumours and Spinal Disease Adrenal Tumours and Spinal Disease This article submitted by Charlie O on 6/14/98. Email Address: My closest friend has been diagnosed with two things that sprung up simultaneously, it seems. He has deg

http://dem0nmac.mgh.harvard.edu/forum/SpinalDisord.

Evaluation: Well-argued articles by Charlie on the 14/06/98 in the Review located in a US academic research database. E-mail link to author and clearly dated well presented with information. Provides good links to authors and associates and further sites on same topics.

4.Chin Med J (Taipei) 1997;60:321-5. (Adrenal Pseudocyst Mim [ Next ] [ Prev ] [ Abs ] [ Chi ] [ TOC ] [ Home ] [Chin Med J (Taipei) 1997;60:321-5.] A Large Adrenal Pseudocyst Mimicking Malignant Intraabdominal Tumour: A Case Report Chung-Tai Yue1, Amy Liao2, Pegg

http://www.vghtpe.gov.tw/~cmj/6006/600607.htm

Evaluation: Well argued articles presented by Chung-Tai Yue, M.D., Department of Pathology and Laboratory Medicine,Shin-Kong Wu Ho-Su Memorial Hospital, No. 95, Wen Chang Road, Shih-Lin, Taipei, Taiwan, R.O.C. Academic research database. E-mail link to author and clearly dated well presented with information. Provides good links to authors and associates and further sites on same topics.

5. ADRENAL DISEASE THERAPY PROTOCOL

PROTOCOLS SEARCH LEF logo ADRENAL DISEASE DISEASE THERAPY PROTOCOL Printing? Use this! Please read this before continuing on: DISCLAIMER THIS INFORMATION (AND ANY ACCOMPANYING PRINTED MATERIAL) IS NO

http://lef.org/protocols/prtcl-002.shtml

Evaluation: produced by the life extension foundation information. Provides good links to authors and associates and further sites that the reader can pursue for further information.

Academic research database. E-mail link to author and clearly dated well presented with information. Provides good links to authors and associates and further sites on same topics.

By M.I.Al-Ruhani,May 2000