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Biosynthesis
Testis - primary site of androgen synthesis in males
Leydig (95%)
both gametogenic & endocrine functions
Adrenals (5%)
Androgens in Females
Physiological significance
- apparently not necessary for normalmenstrual
cycling, but may be involved in pubertal growth
libido
REGULATION OF SECRETION
Regulation of secretion
Oestriol
Pregnenolone 17-- Hydroxy Dehydro-epi
pregnenolone androsterone
TESTOSTERONE OESTRADIOL
Androgens
Negative Feedback
(1) Sex steroids
(2) Inhibin
Physiological effects
(1) Puberty
a. Spermatogenesis
b. Secondary sex characteristics
(2) Protein anabolism
Androgens - Pharmacokinetics
Metabolism
by liver enzymes major pathway
Reduction of double bond and ketone in Ring A
Principally in liver
MOA- Androgens
T- R T- R
10%
90%
T DHT DHT- R
5- reductase
4) Mechanism of action
(1) Plasma protein binding
- 98% of circulating androgen bound to sex hormone
binding globulin
(2) Receptors
a. Gene activation
MOA
Effects - Testosterone & DHT
growth of genitals in a boy
production of sperm
growth of facial, pubic & axillary hairs
muscular development
growth of larynx & voice deepens
inhibition of bone growth
thickening of skin, loss of s.c. fat
behavioral changes in men
erythropoietin secretion increased
Clinical uses of Testosterone
Anaemia (refractory)
Recombinant erythropoietin preferred
Use as growth stimulators
Stimulate growth in boys with delayed puberty
careful use
Aging
Clinical uses of Testosterone
Orally active
Decreases DHT levels in 8 hrs & lasts 24 hrs
T1/2 : 8 hrs
40-50% metabolism
More than half excreted in feces
Benign prostatic hyperplasia reduces size
Treatment of hirsuitism in women
Also used for baldness in males
Dose: 5mg/day
Cyproterone
Cyproterone acetate
Flutamide
Bicalutamide
Nilutamide
Spironolactone
Cyproterone & Cyproterone acetate
Non-steroidal anti-inflammatory
Antagonise androgens:
Accessory sex organs
Pituitary
Uses:
Cancer of prostate along with GnRH agonist
Female hirusitism
Dose: 250 mg tds.
Bicalutamide & Nilutamide
Physiological effects
(1) Puberty
a. Spermatogenesis
b. Secondary sex
characteristics
(2) Protein anabolism
Danazol
FSH & LH release in both sexes
Binding of steroids to receptors
Enzymes needed for steroid synthesis
Weak androgenic, anabolic, progestational & glucocorticoid action
Infertility
Testosterone
Synthesis; The conc. of testosterone in the
plasma of males is relatively high during
three periods of life
1.The phase of embryonic development; it
starts to rise after the 8th week of
development and declines prior to birth
2. The neonatal period: It rises during this
period and after a few months returns to Pre
puberty level
3. At the time of male puberty level it rises
steeply .The feedback inhibition mechanism
becomes insensitive during this period .The
reason for this is unknown.
In men approximately 8 mg of testosterone is
produced daily. About 95% is produced by
the Leydig cells and 5% by the adrenal.
Plasma levels of Testosterone in males are
about 0.6 ug/dl after puberty and declines
after the age of 50.In women it is 0.03 ug/dl
Transport and Metabolism