Transcript Document

In The Name of Almighty Allah
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MALE SEX HORMONES
OH
OH
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TESTO S TERO NE
DIHYDRO TES TO S TERO NE
Natural androgens
ANDROGENS
• Prototype is testosterone
• Main function: Development and maintenance
of primary and secondary sex characteristics in
males (androgenic)
• protein retention (anabolic action)
ANDROGENS
The male sex hormones or androgens are produced by
 Leydig cells of testes in response to LH and
 to a minor extent by adrenal glands in both the sexes.
 Ovaries also produce a small amount of androgens.
Biosynthesis of androgens:
Site: synthesized in the interstitial tissue by the leydig cells.
Precursor: Cholesterol
It is first converted to pregnenolone by cytochrome p450 side
chain cleavage enzyme which then forms androstenedione by
two pathways:
1. Through progesterone (Progesterone (or ∆4) pathway)
2. Through 17-hydroxypregnenolone.(Dehydroepiandrosterone or
∆5 pathway)
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Dehydroepiandrosterone (or ∆5)
pathway,
Progesterone (or ∆4)
pathway
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The conversion of pregnenolone to testosterone requires the action of five
enzyme activities contained in three proteins:
(1) 3β-hydroxysteroid dehydrogenase (3β-HSD) and ∆5,4-isomerase;
(2) 17α-hydroxylase and C17-20 Lyase and
(3) 17β-hydroxysteroid dehydrogenase (17β-OHSD).
The ∆5 route appears to be most used in human testes.
Regulation:
 The production of androgens is under the control of LH and FSH.
 Regulated by negative feedback mechanism
 The rate limiting step is the delivery of cholesterol to IMM by StAR.
Steroidogenic acute regulatory protein (StAR)
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Testosterone is metabolized by two
pathways.
 First pathway involves oxidation at the 17 position,
occurs in many tissues, including liver and produces 17-ketosteroids that are generally
inactive or less active than the parent compound.
 Second pathway (Dihydrotestosterone Is Formed From Testosterone in Peripheral
tissues)
occurs primarily in target tissues
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involves reduction of the A ring double bond and the 3 Ketosterone, a reaction catalyzed
by the NADPH-dependent 5 α reductase
5 mg of testosterone is produced daily by testes. Approximately 400 µg of DHT is
produced daily
 Some estradiol is formed from the peripheral aromatization of testosterone.
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Transport of androgens:
In the plasma testosterone and DHT bind to two proteins1. Sex hormone binding globulin ( SHBG) binds 97 to 99% and
2. Testosterone-estrogen binding globulin( TEBG).
A small fraction is in free form.
Both these proteins are synthesized in liver.
The plasma testosterone level in normal men is about 0.7 µg/dl while in
women it is < 0.1 µg/dl.
Mode of action:
Group I hormone
Both testosterone and dihydrotestosterone bind to a single class of
receptors on the target tissues. The affinity of DHT for the receptor is
much higher compared to testosterone.
Receptor sites for androgens are found in muscle, brain, and other target
tissues.
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Physiological and biochemical functions of androgen:
The androgens influence
1. Growth, development and maintenance of male reproductive
organs.
2. Sexual differentiation and secondary sexual characteristics.
3. Spermatogenesis.
4. Male pattern of aggressive behavior.
5. pubertal transformation:
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Enlargement of testes, penis and scrotum
Pubic and axillary hair
Bone growth
Red cell mass increase
Skeletal muscle mass increase
Larynx enlarges - deepening of the voice
Increase in sebaceous glands - often cause of acne
Development of Beard
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Biochemical functions:
Protein retention ( Anabolic action)
Effect on protein metabolism:
Androgens promote
 RNA synthesis( transcription)
 Protein synthesis( translation).
 Rapidgrowth of musculo-skeletal system associated with puberty.
Effect on carbohydrate and fat metabolism Glycolysis,
 Production of D-fructose from D-glucose by seminal vesicles.
 fatty acid synthesis and
 citric acid cycle.
Effects on mineral metabolismAndrogens promote
 Mineral deposition and bone growth
 Kidney reabsorption of Na+, Cl- and water.
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Abnormalities associated with male sex
hormones:
Hypogonadisn is a disorder characterized by a defect in
testosterone synthesis. It may be of two types.
1. Primary hypogonadism is caused by a failure of testes to
produce testosterone.
2. Secondary hypogonadism is due to an impairment in the
release of gonadotropins.
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All Praise be to HIM, The Lord of the
Universe,The Lord of the day of
Judgment
Thanks a lot
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