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Steroid Hormones
V.S.RAVIKIRAN, MSc.
V.S.RAVIKIRAN, MSc., Department of Biochemistry,
ASRAM Medical college, Eluru-534005.AP, [email protected]
om
Steroid Hormones
Chapter at a Glance
The reader will be able to answer questions on the following topics:Synthesis of steroid hormones17-ketosteroidsBiological effects of glucocorticoidsAssessment of glucocorticoid secretionAdrenal hyper and hypofunctionOvarian hormonesTesticular hormones
ADRENAL CORTICAL HORMONES
• The adrenal cortex has three different zones each responsible for production of different classes of steroid hormones (C21, C19 and C18).Zona glomerulosaZona fascicularisZona reticularis
Zona glomerulosa
• The smallest and outermost zona glomerulosa produces the C21 steroids, mineralocorticoids. They have effects on water and electrolyte balance.
Zona fascicularis
• The middle zone of the adrenal cortex, the zona fascicularis produces the glucocorticoids mainly; and adrenal androgens and estrogens to a lesser extent.
Zona reticularis
• The innermost zona reticularis produces the androgens (C19) and estrogens (C18).
Synthesis of Steroid Hormones
• Cholesterol is first acted upon by desmolase and a 6-carbon unit is cleaved off, forming the 21 carbon steroid, pregnenolone.
Synthesis of pregnenolone
Synthesis of pregnenolone
It is a common precursor for all the steroid hormones.
Adrenocorticotropic hormone (ACTH) stimulates this step.
This is the rate limiting step for synthesis of all steroid hormones.
Progesterone
Progesterone is the first steroid hormone formed from pregnenolone in two steps.
The beta hydroxyl group is converted to a keto group by a 3-beta-oldehydrogenase and the Δ5 double bond shifted to Δ4.
Progesterone
• Progesterone is further converted into glucocorticoids, mineralocorticoids and sex steroids.
Adrenal glucocorticoids
• The major adrenal glucocorticoids are cortisol,cortisone and corticosterone in that order.
• The major mineralocorticoid is aldosterone, but 11-deoxycorticosterone and corticosterone also have significant mineralocorticoid activity.
Adrenal glucocorticoids
These reactions are effected by hydroxylation. These specific hydroxylases are mono-
oxygenases. All these enzymes are NADPH dependent.
Cortisol synthesis
Synthesis of mineralocorticoids
Synthesis of sex hormones
These reactions are effected by hydroxylation. These specific hydroxylases are mono-
oxygenases. All these enzymes are NADPH dependent.The ACTH stimulates the synthesis of all
steroid hormones by activating desmolase so that the availability of pregnenolone is increased.
Transport and Metabolism
• Secretion of all adrenocortical hormones is under the control of ACTH.
• The diurnal variation of secretion of cortisol (highest values early in the morning and minimum at night) parallels the pulsatile release of ACTH from anterior pituitary under the influence of CRF.
Transport and Metabolism
• Cortisol exerts the negative feedback effect on ACTH secretion.
• The ACTH also increases the secretion of aldosterone.
Transport and Metabolism
• The level of aldosterone is also affected by position, highest values in upright posture and lowest while lying down.
• All steroid hormones act through intracellular messengers and increase the rate of transcription.
Transport and Metabolism
• Approximately 70% of cortisol in blood is bound to an alpha-1-globulin called cortisol binding globulin (CBG) or transcortin.
• About 20% is bound to albumin and the rest is free, which is the biologically active fraction.
• The half-life of cortisol is about 2 hours.
Transport and Metabolism
• The steroid hormones are metabolized and inactivated by the liver.
• The major processes are reduction and conjugation.
• The C21 steroids are reduced to their tetrahydro derivatives, which are excreted as their glucuronides or sulfates in urine.
Urinary Steroids
• The urinary steroids are referred to as 17-ketosteroids and 17-hydroxy steroids.
• The 17-ketosteroids may be derived from both adrenal steroids and androgens from the gonads.
• The 17-hydroxy steroids are directly derived from the adrenal steroids (glucocorticoids and mineralocorticoids).
Urinary Steroids
Summary of major pathways for production ofglucocorticoids, mineralocorticoids and sex steroids. Precursorsin red box; intermediaries in gray box; hormones in blue box;excretory products in brown box
Biological Effects of Glucocorticoids
• The glucocorticoids, as the name suggests, mainly affect metabolism of glucose. The major biological effects of glucocorticoids are given in Table.
Effects of glucocorticoids
Biological Effects of Mineralocorticoids
Mineralocorticoids (mainly aldosterone) increases sodium reabsorption from renal tubules, leading to sodium retention and resultant water retention, acting through RAS.
The sodium potassium exchange at the renal tubules lead to increased potassium excretion.
Mechanism of Action of Steroid Hormones
Steroid hormones in general have nuclear receptors and act by regulation of gene expression.
Steroid hormones being lipid soluble can easily pass through plasma membrane and enter the cytoplasm.
Here they combine with specific receptors and the HR complex translocates to the nucleus.
Mechanism of Action of Steroid Hormones
The steroid hormone response elements on DNA (specific sequences bind specific hormones) and regulate transcription of genes.
The proteins produced in response to the hormonal stimulation produce metabolic effects, e.g. enzymes and transporters.
Adrenal Hyperfunction
• Hyperactivity of adrenal cortex may be due to primary defect in adrenal gland itself (Cushing’s syndrome) or secondarily by excessive production of ACTH from pituitary (Cushing’s disease) or ectopic ACTH production by other malignant tumors
Adrenal Hypofunction
The most common cause of adrenal hypofunction is primary adrenal insufficiency or Addison’s disease.
It is characterized by tiredness, dehydration, hyponatremia and hyperpigmentation (due to high ACTH levels and its MSH activity).
Primary Hyperaldosteronism(Conn’s Syndrome)
• This may result from an aldosterone secreting tumor. The condition may be diagnosed by:
a. Elevated plasma aldosterone levels and no change with posture
b. Plasma renin activity is decreased due to feedback effect
c. Serum electrolytes show hypernatremia and hypokalemia
Primary Hyperaldosteronism(Conn’s Syndrome
d. Plasma pH is elevated (hypokalemic alkalosis).
e. Osmolality is elevated (hypertonic expansion).
Adrenogenital Syndrome (AG Syndrome)
• There is congenital deficiency of steroid hydroxylases leading to deficient secretion of cortisol.
• Since cortisol, the major feedback effector is not present, ACTH secretion continues leading to adrenal hyperplasia (CAH).21- Hydroxylase deficiency11-Hydroxylase deficiency
SEX HORMONES
• These are secreted by the gonads in response to pituitary gonadotropins (LH and FSH).
Ovarian Hormones
They are C18 estrogens, C19 androgens and C21 progesterone. These are produced by the ovarian follicles.
Estradiol is the most important estrogen.Estradiol has not only a critical impact on
reproductive and sexual functioning, but also affects other organs including the bones.
Testicular Hormones In humans, testosterone is the major male
hormone.The Leydig cells (interstitial cells), secrete the
androgens, under the influence of LH.Androgens stimulate spermatogenesis, produce
hypertrophy of prostate, seminal vesicles, muscle, bone and kidney cells. It is anabolic.
Dihydrotestosterone (DHT) is the cause for the benign prostate hypertrophy, that affects more than 75% of men over the age of 60 years.
Summary of steroid hormones
THE END
THANKS FOR YOUR ATTENTION
