ADRENAL PHYSIOLOGY ADRENAL GLAND - PowerPoint Presentation

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ADRENAL PHYSIOLOGY

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ADRENAL GLAND

The adrenal gland is one of the body’s main endocrine glands.

It consists of a cortex and medulla.The cortex has three layers which each secrete a different class of steroid.The medulla secretes neurochemicals.

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ADRENAL GLAND

Zona glomerulosa:

(15% of cortex). Secretes mineralocorticoids eg. Aldosterone (contains aldosterone synthase) Zona fasiculata: (75% of cortex). Secretes glucocorticoids eg. Cortisol & Corticosterone. As well as small amounts of estrogens

& adrenal androgens. Stimulated by

ACTH.

Zona reticularis: Secretes the adrenal androgens dehydroepiandrosterone (DHEA) and androstenedione as well as small amounts of estrogens and some glucocorticoids. ACTH also regulates secretion of these cells.

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CORTICOSTERIOD SYNTHESIS

All human steroids are from

cholesterol.Adrenocortical cells can produce cholesterol on their own, but 80% of the cholesterol used for corticosteroid synthesis is from LDL delivered to the cells by blood plasma.ACTH increases the amount of receptors for LDL on the

adrenocortical cells

as well as the

activity of enzymes which allow cholesterol to be removed from LDL in the cell.

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CORTICOSTERIOD SYNTHESIS

Cholesterol

enters the mitochondria where it is cleaved by the enzyme cholesterol desmolase to form pregnenolone which includes STAR proteins responsible for allowing the cholesterol to enter the mitochondria – Rate limiting step.In all three zones, this initial step in steroid synthesis is stimulated by the different factors that control secretion of the major hormone products aldosterone and cortisol. (ACTH, K+

or ANGIOTENSIN II)

Cholesterol ----------

----------------> Pregnenolone

cholesterol desmolase

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CORTICOSTERIOD SYNTHESIS

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CORTICOSTERIOD TYPES

ADRENAL

STEROIDTYPE

CORTISOL

GLUCOCORTICOID

SLIGHT MINERALOCORTICOIDCORTICOSTERONEGLUCOCORTICOIDSLIGHT MINERALOCORTICOID

ALDOSTERONE

MINERALOCORTICOID

DEXOYCORTICOSTERONE

MINERALOCORTICOID

DEHYDROEPIANDOSTERONE

ADRENAL ANDROGEN

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SYNTHETIC STEROID

TYPE

CORTISONE

GLUCOCORTICOID

SLIGHT MINERALOCORTICOID

PREDNISOLONEGLUCOCORTICOID4X CORTISOL POTENCY

METHYL

PREDNISONE

GLUCOCORTICOID

5X CORTISOL

POTENCY

DEXAMETHASONE

GLUCOCORTICOID

30X CORTISOL POTENCY

9 ALPHAFLUOROCORTISOL

MINERALOCORTICOID

CORTICOSTERIOD TYPES

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CORTICOSTERIOD TRANSPORT

Generally, adrenocortical hormones are bound to plasma proteins.

~90% of cortisol secreted is bound to transcortin/ cortisol binding globulin and albumin~60% of aldosterone secreted binds to plasma proteinsCortisol therefore has a greater half life than aldosterone.

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CORTICOSTERIOD BREAKDOWN

Corticosteroids are broken down in the liver by conjugation to

glucoronic acid and to a lesser extent sulfates.These substances are inactive.~25% is eliminated through bile and then feces.The rest is highly soluble and eliminated therefore by the

kidneys.

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MINERALOCORTICOID FUNCTION

Aldosterone

increases renal absorption of sodium and excretion of potassium in the principal cells of the collecting tubules mainly.Sodium is exchanged for hydrogen

in the tubules therefore aldosterone causes a

slight alkalosis

due to the excretion of hydrogen.

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MINERALOCORTICOID FUNCTION

Aldosterone stimulates

absorption of sodium & excretion of potassium in sweat glands & salivary glands.Aldosterone increases renal absorption of sodium in the intestines (especially in the colon)

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MINERALOCORTICOID CELLULAR MECHANISM

The events are still not fully understood.

- Aldosterone is lipid soluble therefore it diffuses into the interior of the principal cells of the collecting tubules.- Aldosterone then binds to a highly specific cytoplasmic receptor.- The aldosterone receptor complex, or a product of the complex

diffuses

into the

nucleus.

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MINERALOCORTICOID CELLULAR MECHANISM

- Then it

induces parts of DNA to form RNA involved in sodium, hydrogen & potassium transport.- The proteins formed are enzymes or membrane transport proteins that are responsible for sodium, potassium and hydrogen transport.

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MINERALOCORTICOID CELLULAR MECHANISM

The enzyme

Sodium potassium ATPase is one of the proteins greatly increased.This enzyme is the principal part of the sodium potassium ATP-ase pump which serves to exchange sodium for potassium at the basolateral

aspects of the cells.

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MINERALOCORTICOID REGULATION

Four factors are known to play essential roles in the regulation of aldosterone:

Increased potassium in the ECF stimulates aldosterone secretion. (most potent)Increased angiotensin II stimulates aldosterone secretion (most potent)Increased sodium in ECF slightly decreases aldosterone secretionACTH is necessary but has little effect in controlling the rate of secretion. Only needed to start the process.

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GLUCOCORTICOID FUNCTION

The best known effect of glucocorticoids on

metabolism is that it stimulates gluconeogenesis in the liver.Cortisol increases the formation of enzymes needed to convert amino acids into glucose in the liver

Cortisol also causes the

mobilization of amino acids

from extra-hepatic tissue; mainly muscle.

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GLUCOCORTICOID FUNCTION

Cortisol causes

decreased glucose utilization by cells. The mechanism is unknown.Cortisol causes an increase in blood glucose concentration due to previous effects. For unknown reasons cortisol impairs the functionality of insulin when the blood sugar is too high.

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GLUCOCORTICOID FUNCTION

- Cortisol

reduces protein stores in all cells except the liver by decreased synthesis & increased catabolismCortisol increases liver & plasma proteins- Mobilization of fatty acids from adipose tissue, thereby increasing its

use as energy

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GLUCOCORTICOID FUNCTION

Generally speaking,

Cortisol helps shift the metabolism of the body from using glucose for energy to using fatty acids in times of stress, to conserve glucose for future use in the event that no glucose is taken into the body.

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GLUCOCORTICOID CELLULAR MECHANISM

- Cortisol is

lipid soluble therefore it diffuses into the target cells.- Cortisol then binds to a protein cytoplasmic receptor.

- The cortisol receptor complex then

diffuses

into the nucleus where it interacts with specific regulatory DNA sequences called glucocorticoid response elements.

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GLUCOCORTICOID REGULATION

Hormones involved:

CRH (Corticotropin-releasing hormone) is a peptide composed of 41 amino acids. The cell bodies of the neurons that secrete CRH are located mainly in the paraventricular nucleus of the

hypothalamus.

This nucleus in turn

receives many nervous connections from the limbic system and lower brain stem.

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GLUCOCORTICOID REGULATION

Hormones involved:

ACTH is a peptide composed of 39 amino acids. ACTH is secreted by the cells of the adenohypophysis.

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GLUCOCORTICOID REGULATION

Corticotropin

-releasing hormone (CRH) is secreted into the primary capillary plexus of the hypophysial portal system and then carried to the anterior pituitary gland where it induces

ACTH secretion.

ACTH

then in turn stimulates the production of cortisol from the zona fasiculata of the adrenal cortex.The principal effect of ACTH is to bind to receptors in the cell membranes of the zona

fasiculata

cells to activate

adenyl

cyclase

thereby activating the

cAMP

secondary messenger system.

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GLUCOCORTICOID REGULATION

The

cAMP activates intracellular hormones which then cause the production of the steroid hormones.The most important of all the ACTH-stimulated steps for controlling adrenocortical secretion is activation of the enzyme protein kinase A,

which causes initial conversion of

cholesterol to pregnenolone.

This initial conversion is the “rate-limiting” step for all the adrenocortical hormones.

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GLUCOCORTICOID REGULATION

Cortisol has

direct negative feedback effects on.The hypothalamus to decrease the formation of CRF The anterior pituitary gland to decrease the formation of ACTH. - Both of these feedbacks help regulate the plasma concentration of cortisol.

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ADRENAL ANDROGENS

Several

moderately active male sex hormones called adrenal androgens (the most important of which is DHEA dehydroepiandrosterone) are continually secreted by the adrenal cortex, especially during fetal life.Made in the Zona reticularis.Progesterone and estrogens which are female sex hormones, are secreted in minute quantities. Normally, the adrenal androgens have

only weak effects in humans.

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Questions

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Questions