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Steroid Hormones
V.S.RAVIKIRAN, MSc.
V.S.RAVIKIRAN, MSc.,
Department of Biochemistry,
ASRAM Medical college,
Eluru-534005.AP, India.
vsravikiran2013@gmail.com
Steroid Hormones
Chapter at a Glance
The reader will be able to answer questions
on the following topics:
Synthesis of steroid hormones
17-ketosteroids
Biological effects of glucocorticoids
Assessment of glucocorticoid secretion
Adrenal hyper and hypofunction
Ovarian hormones
Testicular 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 glomerulosa
Zona fascicularis
Zona 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 of
glucocorticoids,
mineralocorticoi
ds and sex
steroids.
Precursors
in 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 deficiency
11-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

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Steroid hormones

  • 2. V.S.RAVIKIRAN, MSc., Department of Biochemistry, ASRAM Medical college, Eluru-534005.AP, India. vsravikiran2013@gmail.com
  • 4. Chapter at a Glance The reader will be able to answer questions on the following topics: Synthesis of steroid hormones 17-ketosteroids Biological effects of glucocorticoids Assessment of glucocorticoid secretion Adrenal hyper and hypofunction Ovarian hormones Testicular hormones
  • 5. 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 glomerulosa Zona fascicularis Zona reticularis
  • 6. Zona glomerulosa • The smallest and outermost zona glomerulosa produces the C21 steroids, mineralocorticoids. They have effects on water and electrolyte balance.
  • 7. 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.
  • 8. Zona reticularis • The innermost zona reticularis produces the androgens (C19) and estrogens (C18).
  • 9. 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.
  • 11. 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.
  • 12. 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.
  • 14. • Progesterone is further converted into glucocorticoids,  mineralocorticoids and sex steroids.
  • 15. 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.
  • 16. Adrenal glucocorticoids These reactions are effected by hydroxylation. These specific hydroxylases are mono- oxygenases. All these enzymes are NADPH dependent.
  • 20. 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.
  • 21. 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.
  • 22. Transport and Metabolism • Cortisol exerts the negative feedback effect on ACTH secretion. • The ACTH also increases the secretion of aldosterone.
  • 23. 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.
  • 24. 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.
  • 25. 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.
  • 26. 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).
  • 28. Summary of major pathways for production of glucocorticoids, mineralocorticoi ds and sex steroids. Precursors in red box; intermediaries in gray box; hormones in blue box; excretory products in brown box
  • 29. 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.
  • 31. 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.
  • 32. 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.
  • 33. 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.
  • 34. 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
  • 35. 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).
  • 36. 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
  • 37. Primary Hyperaldosteronism (Conn’s Syndrome d. Plasma pH is elevated (hypokalemic alkalosis). e. Osmolality is elevated (hypertonic expansion).
  • 38. 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 deficiency 11-Hydroxylase deficiency
  • 39. SEX HORMONES • These are secreted by the gonads in response to pituitary gonadotropins (LH and FSH).
  • 40. 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.
  • 41. 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.
  • 42. Summary of steroid hormones
  • 43. THE END THANKS FOR YOUR ATTENTION