1. Steroid Hormones

2. Objectives Recall the overall role of steroids in human body.
Understand the physiological roles of cholesterol especially in synthesis of steroid hormones.
Recall the biochemical and clinical aspects of all types of adrenal steroids.
Explain with appropriate details the biochemical and physiological aspects of steroids from the testis and ovaries
Recognize the biochemical and clinical relations of congenital adrenal hyperplasia and testicular feminization syndrome

3. Steroid Hormones Types of steroid hormones:
Glucocorticoids: cortisol is the major representative in most mammals
Mineralocorticoids: aldosterone being most prominent
Sex hormones:
Androgens: such as testosterone
Estrogens: including estradiol & estrone
Progestogens: also known a progestins such as progesterone

4. Steroid Hormones Steroid hormones are synthesized in:
All steroid hormones are:
Derived from cholesterol
& differ only in the ring structure & side chains attached to it.
Lipid soluble & thus are freely permeable to membranes so are not stored in cells
Steroid hormones are synthesized in:
Adrenal cortex: cortisol, aldosterone & androgens (androstendione)
Testis: testosterone
Ovaries: estrogens & progesterone
Placenta: progesterone
Some peripheral tissues (as adipose tissue & the brain)

5. Steroid Hormones
Cholesterol
is the precursor of
steroid hormones

6. Transport of Steroid Hormones in Blood
Steroid hormones have to be carried in the blood complexed to specific binding plasma proteins (globulins).
Cortisol: by corticosteroid binding globulin (transcortin)
Sex steroids (testosterone & estradiol): by sex hormone-binding protein (SHBG)
Aldosterone: by the plasma protein albumin

7. General Functions of Steroid Hormones
Steroid hormones play important roles in:
Metabolic regulation (glucocorticoids i.e. cortisol)
Electrolyte balance (mineralocorticoids i.e. aldosterone)
Reproductive functions (gonadal steroids i.e. testosterone & estrogens)
Steroids also play roles in:
Inflammatory responses
Stress responses
Bone metabolism
Cardiovascular fitness
Behavior, cognition & mood

8. Steroid Hormone Synthesis
A series of enzymatic steps in the mitochondria & ER of steroidogenic tissues convert cholesterol into all of the other steroid hormones & intermediates.
An important control point this process is the transport of free cholesterol from the cytoplasm into mitochondria.
This step is carried out by the Steroidogenic Acute Regulatory Protein (STAR)

9. Sources of Cholesterol for Steroid Synthesis
Lipoproteins in Blood
Sources of Cholesterol for Steroid Synthesis LH
Acetyl CoA
Cholesterol pool
ATP
cholesterol
cAMP
Protein
Kinase
mitochondria
STAR
Desmolase
Pregnenolone
Pregnenolone
In:
Adrenal Cortex
Testis
Ovary
ALL STEROID HORMONES

10. Steroid Hormone Synthesis
The first enzymatic step is
the conversion of cholesterol to pregnenolone
which occurs in the mitochondria.
This reaction is carried out by the enzyme desmolase
This is a rate limiting, nonreversible step
in the initiation of steroid biosynthesis.
This step occurs in
Adrenal Cortex, Ovary & Testis

11. Steroid hormone synthesis in the Adrenal Cortex

12. The adrenal gland is composed of the adrenal cortex & adrenal medulla
Organization of the Adrenal Gland
The adrenal gland is composed of the adrenal cortex & adrenal medulla
1- The adrenal cortex:
The zona glomerulosa: secretes aldosterone
The zona fasciculata: secretes cortisol
The zona reticularis: secretes the adrenal androgens
2- The adrenal medulla:
Secretes adrenaline (epinephrine)
As you knowthe adrenal gland is:

13. Cholesterol Steroid Hormone Synthesis In Adrenal Cortex Pregnenolone
Desmolase
Pregnenolone
3-β-Hydroxysteroid dehydrogenase
Progesterone
21-α-Hydroxylase
17-α-Hydroxylase
17-α-Hydroxyprogesterone
11-Deoxycorticosterone
androgen
21-α-Hydroxylase
Androstenedione
11- β -Hydroxylase
11-Deoxycortisol
Testosterone
Corticosterone
NOT IN
ADRENAL
CORTEX
Peripheral
Tissues
Aldosterone
Cortisol
Estradiol

14. Regulation of Cortisol Secretion from the Adrenal Cortex
Negative feedback control:
ACTH release from the anterior pituitary is stimulated by hypothalamic secretion of corticotrophin releasing hormone (CRH).
CRH   ACTH   Cortisol
 Cortisol (or synthetic steroids)
Suppress CRH & ACTH secretion
Hypothalamus
Pituitary
Adrenal

15. Testosterone Production in the Testis

16. Pathway of Testosterone Production in the Testis
The production of androgens from cholesterol is identical to that in the adrenal, except that it continues from androstenedione to testosterone.
Cholesterol
In the Testis
Androstenedione
Testosterone
17b-hydroxysteroid
Oxidoreductase
N.B. In the adrenal cortex, androstendione (adrenal androgen) is formed.
They are released to blood & converted in the testis (& peripheral tissues)
to testosterone

17. Pathway of Testosterone Production in the Testis
The main steroid produced in the male is testosterone produced from the testis. .
In the male, there is peripheral conversion of testosterone to:
Dihydrotestosterone: in androgen target tissues, like muscles by 5 a reductase
Or to
Estradiol : mostly in adipose tissue by enzyme cytochrome P450 aromatase

18. Control of Testicular Function by the Pituitary Gonadotrophins (LH & FSH)
Hypothalamus
GnRH LH
++ testosterone synthesis in testis
FSH
++ spermatogenesis in testis + -
Anterior Pituitary
FSH LH + +
Testis
Testosterone
++ Spermatogenesis
++ Development of secondary
male sex characters
++ Anabolism
Testosterone
Spermatogenesis +

19. Synthesis of Steroid Hormones in the Ovary

20. Synthesis of Steroid Hormones in the Ovary
Estradiol is formed from the conversion of androgens (testosterone) into
estradiol by the enzyme cytochrome P450 aromatase (in granulosa cells).
The androgens required for conversion come from the neighboring theca
cells.
Cholesterol
Theca Cells
Androstendione Testosterone Estradiol
Aromatase
Stimulated by FSH
Stimulated
by LH
Granulosa Cells of the Ovary

21. Synthesis of steroid Hormones in the OvaryLH
++ estrogen secretion
++ ovulation
FSH
++ secretion of estrogen
Regulates growth of ovarian follicle
Theca
cells
Granulosa LH
LH receptor
cholesterol
Androstendione
Androstendione Testosterone
FSH
aromatase
Estradiol
FSH receptors
LH & FSH stimulates estrogen secretion
FSH regulates growth of ovarian follicles
LH stimulates ovulation

22. Mechanism of Action of Steroid Hormones
Cytosolic
Receptors
Hormone Receptor
Complex
HRE
of genes
Transcription
of genes
is increased

23. Congenital Adrenal Hyperplasia (CAH)
It is the result of an inherited enzyme defect in steroid hormones biosynthesis in the adrenal cortex.
The Adrenal Cortex :
Cannot secrete cortisol  absent negative feedback to the pituitary)  ACTH continues to drive steroid biosynthesis  adrenal hyperplasia & accumulation of cortisol precursors (depending on which enzyme is lacking)
Cannot secrete aldosterone  electrolyte disturbances
The condition might be fatal unless diagnosed early

24. 21 -Hydroxylase Deficiency
17-hydroxy-progesterone
Progesterone
Androstenedione In
Peripheral Tissues
21 -hydroxylase
11-deoxycorticosterone
11-deoxycortisol
Testosterone
Aldosterone
Cortisol
Precocious
sexual development
in ♂
Virilisation
of ♀

25. 21 -Hydroxylase Deficiency
Accounts for ~ 95% of all cases of CAH
Autosomal recessive condition
Low or absent synthesis of Cortisol & Aldosterone
 Cortisol  ACTH secretion  Adrenal Gland hyperplasia
Some of the accumulated precursors are diverted to the biosynthesis of sex hormones  Signs of Androgen Excess:
 stimulation of adrenal androgen production  virilisation in baby girls &
precocious puberty in boys
In severe cases, Aldosterone Deficiency is evident  salt & water loss  hypovolaemia & shock  neonatal adrenal crisis