ADRENAL GLANDS AND HORMONES

Adrenal glands

The adrenals are orange-colored glands that sit on top of the

kidneys near the spine, just underneath the last rib and extending

down about an inch. The right adrenal is shaped something like a

pyramid, whereas the left is shaped more like a half moon.

Adrenal glands – paired, pyramid-shaped organs atop the kidneys

Weigh 6-10 g.Structurally and functionally, they are two glands in oneAdrenal cortex (80-90%)– glandular tissue derived from embryonic mesoderm

Adrenal medulla (10-20%)– formed from neural ectoderm, can be considered a modified sympathetic ganglion

Adrenal medulla (inner part) that

constitutes 20% of the gland and a

cortex (outer part) that constitutes the

remaining 80%. The cortex consists

of three zones. The medulla and each

of the zones in the cortex each

produce different hormones that serve

a variety of functions in our body.

ADRENAL GLANDS

The Adrenal Cortex

The adrenal cortex is divided into

three zones which each secrete

different hormones that carry out

specific functions throughout body.

1. Zone of glomerulosa Aldosterone is secreted from this zone which is the major hormone

controlling the sodium and potassium levels, and thus fluid balance,

within bloodstream, cells and interstitial fluids. It is also called

mineralocorticoids.

3

2

Medulla

Cortex

1. Zone of glomerulosa

The Adrenal Cortex

2. Zone of fasciculata Coritsol (hydrocortisone) is produced,

affects glucose, amino acid and fat

metabolism, which is called glucocorticoids.

Cells of this zone are arranged into fascicles

separated by venous sinuses.

3. Zone of reticularis

Dehydroepiandrosterone (DHEA)-precursor for androgen is

synthesized. This zona manufactures an ancillary portion of sex

hormones for each sex and also produces male hormones in women

and female hormones in men to keep the effects of the dominant sex

hormones in balance .

3

2

Medulla

Cortex

1. Zone of glomerulosa

ADRENALS

Zona ReticularisSex steroids (androgens)

Zona FasciculataGlucocorticoids (Cortisol)

Glucose homeostasis and many others

Zona Glomerulosa

Mineralocorticoids (Aldosterone)

Na+, K+ and water homeostasis

Medulla: “Catecholamines”Epinephrine, Norepinephrine

CORTEX

Synthesis of adrenocorticosteroids

All steroid hormones have in common the 17-carbon cyclopentao-

perhydrophenanthrene nucleus. Additional carbons can be added at

positions 10 and 13 or as a side chain attached to C17.

1. Uptake of cholesterol by the adrenal cortex is mediated by the LDL receptor. With long-term stimulation of the adrenal cortex by ACTH, the number of LDL receptors increases. Much of the cholesterol in the adrenal is esterified and stored in cytoplasmic lipid droplets.

2. 2. Upon stimulation of the adrenal by ACTH or cAMP, an esterase is activated, and the free cholesterol formed is transported into the mitochondria.

3. In the mitochondria, a cytochrome P450 side chain cleavage

enzyme (P450scc) converts cholesterol to pregnenolone.

Synthesis of adrenocorticosteroids

4. Pregnenolone may be converted by dehydrogenase/isomerase to progesterone or else by P450c17 (17-α-hydroxylase) to 17α-hydroxypregnenolone. Progesterone can also be converted to 17α-hydroxyprogesterone by P450c17.

Synthesis of adrenocorticosteroids

17-α-hydroxylase

17-α-hydroxylase

dehydrogenase/isomerase

5. After the synthesis of progesterone and 17-hydroxyprogesterone, P450c21(21-hydroxylase) can hydroxylate these steroids at the 21 position, resulting in 11-deoxycorticosterone and 11-deoxycortisol, respectively.

Synthesis of adrenocorticosteroids

21-hydroxylase

21-hydroxylase

6. The final step in the synthesis of adrenal mineralocorticoids and glucocorticoids is mediated by P450c11 (11-β-hydroxylase), which also mediates the final steps in the synthesis of aldosterone from deoxycorticosterone.

11-β-hydroxylase

11-β-hydroxylase

11

7. P450c17 has two activities, that of a 17α-hydroxylase and that of a C-

17,20 lyase capable of breaking up the C-17,20 carbon bond of 17α-

hydroxypregnenolone or 17α-hydroxyprogesterone, yielding

dehydroepiandrosterone (DHEA) or androstenedione, respectively.

Synthesis of adrenocorticosteroids

Synthesis of adrenocorticosteroids

8. 17-hydroxysteroid dehydrogenase convert androstenedione to

testosterone. P450 also mediates the aromatization of androgens to

estrogens in the gonads. In peripheral target tissues, testosterone can

further be converted to 5α-dihydrotestosterone by 5α-reductase.

Biosynthesis

Of human

steroid

Hormones

Biochemical actions of adrenocorticosteroids

A. Mineralocorticoids: aldosterone

It promotes Na+ reabsorption at the distal

convoluted tubules of kidney. Na+ retention

is accompanied by corresponding excretion

of K+,H+ and NH4+ ions.

Biochemical actions of adrenocorticosteroids

B. Glucocorticoids: Cortisol

Biochemical actions of adrenocorticosteroids

1. Effects on glucose metabolism: They promote gluconeogenesis.

They work in tandem with insulin from the pancreas to maintain blood

glucose levels in the proper balance.

2. Effects on lipid metabolism: They increase lipolysis in adipose

tissue and reduce synthesis of TAG.

3. Effects on protein and nucleic acid metabolism: They promote

transcription and protein synthesis in liver. They also cause catabolic

effects in extrahepatic tissues results in enhanced degradation of protein

B. Glucocorticoids: Cortisol

4. Effects on water and electrolyte metabolism: Deficiency of them

cause increased production of ADH which can decrease glomerular

filtration rate causing water retention in the body.

5. Effects on immune system: Cortisol suppress the immune response

directly and indirectly by affecting most cells that participate in immune

reactions and inflammatory reactions. It is powerful anti-inflammatory

even when secreted at normal levels. It also reduces the rate at which

lymphocytes multiply and accelerates their programmed cell death to

further protect the body from this overreaction. This is one of the

reasons why strong corticosteroids (prednisone, prednisolone, etc.) are

used with all diseases involving inflammatory processes, including

auto-immune diseases.

6. Effects on cardiovascular system: Cortisol could control the

contraction of the walls of the mid-sized arteries in increasing blood

pressure, but this hypertensive effect is moderated by calcium and

magnesium. It also directly affects the heart by regulating sodium and

potassium in the heart cells and increasing the strength of contraction of

the heart muscle.

7. Effects on central nervous system: The changes of behavior, mood,

excitability and even the electrical activity of neurons in the brain

frequently occur in cases of excess and deficient cortisol levels. Many

signs and symptoms of adrenal fatigue involve moodiness, decreased

tolerance, decreased clarity of thought and decreased memory. These

occur because the brain is affected by both too little and too much

cortisol.

There are four major categories of stress:

1. Physical stress: such as overwork, lack of sleep, athletic

overtraining. 2.Chemical stress: environmental pollutants, allergies to

foods, diets high in refined carbohydrates, endocrine gland imbalances.

3. Thermal stress: over-heating or over-chilling of the body

4. Emotional and mental stress

Stress

Adrenal glands are the anti-stress glands of the body.

Stress: During stress cortisol must

simultaneously provide more blood glucose,

mobilize fats and proteins for a back-up

supply of glucose, modify immune reactions,

heartbeat, blood pressure, brain alertness and

nervous system responsiveness. If cortisol

level cannot rise in response to these needs,

maintaining your body under stress is nearly

impossible.

Adrenals

Kidney

Posterior Pituitary Gland

Hypothalamus

AnteriorPituitary Gland

ACTH

Stress Circadian

rhythm

CRH

(-)

Glucocorticoids, Catecholamines, etc..

Glucocorticoids, Catecholamines, etc..

Muscle: Net loss of aminoAcids (glucose)

Liver: Deamination of

proteins into amino acids,

gluconeogenesis (glucose)

Fat Cells: Free fatty

acid mobilization

Heart rate: Increased

Immune system: altered

Hypothalamopituitary adrenal (HPA) axis

(Figure 9-40)

Fasting

People have considerable difficulty when on a prolonged fasting.

They will always rationalize the problems encountered on a fasting

as being due to the body detoxifying.

During a fasting, the body will call on the adrenals to produce

glucocorticoids to maintain blood glucose level which is adequate for

normal level of activity. The glucocorticoids can elevate blood

glucose by breaking down protein into carbohydrates through the

process of gluconeogenesis.

THE GENERAL ADAPTATION SYNDROME

Regulation of glucocorticoids

The Secretion of glucocorticoids from the adrenal cortex is regulated

by negative feedback involving the CRH secretion by the

hypothalamus. CRH then acts on the anterior pituitary to stimulate

ACTH secretion, which then stimulates the adrenal cortex into cortisol

secretion. About 70% of blood cortisol is bound to a carrier protein

called corticosteroid-binding globulin. Another 15% is bound to

albumin, the remaining 15% exists free in blood.

The HPA axis or HPA system, a negative

feedback system, is one of the most important

elements of homeostasis, the process that

maintains a steady internal biochemical and

physiological balance in our body. The HPA

Axis adjusts cortisol level according to the needs

of the body, under normal and stressed

conditions, via ACTH. ACTH is secreted from

the pituitary gland in response to orders from the

hypothalamus and travels in the bloodstream to

the adrenal cortex.

※ The Hypothalamus/Pituitary/Adrenal (HPA) Axis

The Adrenal Medulla

The functional unit of the adrenal

medulla is the chromaffin cell, which

functions as a neuroendocrine cell. In

response to stimulation, chromaffin cells

secrete the hormones epinephrine

(adrenaline) and norepinephrine

(noradrenalin) directly into the blood.

The medulla is involved in extreme stress and, within this context,

epinephrine and norepinephrine both work with cortisol from the

adrenal cortex. Epinephrine and norepinephrine are important mainly in

crisis situations.

1

3

2

Medulla

Cortex

CATECHOLAMINES BIOSYNTHESIS

1. Tyrosine is precursor for the synthesis of catecholamines.

2. The catecholamine are produced in response to fight,

fright and flight (3F). These include emergencies like

shock, cold, fatigue, emotional condition like anger.

BIOCHEMICAL FUNCTION OF CATECHOLAMINE1. Effect on carbohydrate metabolism: Both of them can increase

glycogenolysis and gluconeogenesis and decrease glycogenesis.①Catecholamine promote the release of glucose from liver and

decrees its utilization by muscle; Epinepherine inhibits insulin ②secretion but promote glucagon secretion.

2. Effect on lipid metabolism: Both of them enhance the breakdown of TAG in adipose tissue. This cause increase in the free fatty acid in the circulation which are effectively utilized by the heart and muscle as fuel source.

3. Effect on physiological function: Cateccholamines increase cardiac output, blood pressure and oxygen consumption. They cause smooth muscle relaxation in bronchi, GIT and blood vessels supplying skeletal muscle.