Gonad Hormones : Male
Prof.Dr.Gülden Burçak
2011-2012
Testis
 male sex hormones
 male germ cells
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Testis : two functional units
 Semineferous
tubules lined with Sertoli
cells and germ cells (spermatogonia) for
production and transport of sperm .
Sertoli cells provide the environment
necessary for germ cell differentiation
and maturation
 Interstitial cells ( Leydig cells) for
production of testosterone.
Hypothalamic-Pituitary-Testis Axis
Constant pulsatile release of GnRH from
the hypothalamus
 Synthesis, storage and secretion of
gonadotropins (FSH and LH) from the
anterior pituitary
 (-)feedback relationship between the
androgens and GnRH, FSH, LH
secretions
 Prolonged exposure to LH results in
desensitization
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In childhood
 testosterone and plasma gonadotropin levels are low
 HPA is highly sensitive to (-) feedback effects of
gonadal steroids
 Onset of puberty
 Bursts of GnRH release
 Sleep associated surges in LH secretion and to a
lesser extent in FSH secretion
 Later in puberty pulsatile gonadotropin secretion
throughout the day and night and more sustained
plasma gonadotropin, testosterone and
dihydrotestosterone
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For normal testicular function, GnRH pulses
occur at a frequency of 3.8 pulses every 6
hours.
 At a lower pulse rate FSH release ; at a
higher pulse rate LH is more prominent
 Circulating half-life : FSH,4 hours ; LH, 30
minutes
 Testosterone : diurnal rythmic pattern,
highest in the early morning
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LH
binds Leydig cells
testosterone synthesis and secretion
secretion is inhibited by both testosterone and
estradiol
conversion of testosterone to estradiol in brain,
pituitary and testes
FSH
binds Sertoli cells
synthesis of androgen binding protein, aromatase
enzyme complex, inhibin
secretion is primarily inhibited by inhibin B but also
by testosterone
Testosterone biosynthesis
Cholesterol
 de novo synthesis or from LDL
 cholesterol esters storage in cytoplasm
 LH (cAMP) (acute) : esterase activation
and cholesterol transport to the inner
mitochondrial membrane (steroidogenic
acute regulatory protein (StAR)
 LH (cAMP) (chronic) : steroidogenic
enzyme synthesis
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Side chain cleavage and removal of the
six-carbon fragment
 Cytochrome P450 side chain cleavage
 Two hydroxylations first at C22 then at
C20 (O2 and NADPH)
 Cholesterol 20,22- desmolase
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5α-reductase,type I : liver
Type II : reproductive tissues and peripheral targets
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Daily testicular production
5mg testosteron,
50-100μg DHT ; %25 of DHT in circulation
%25 of estradiol (E2) in circulation
Testosterone : a circulating precursor of DHT
and E2
DHT (5α-reductase) in liver, kidney, muscle,
prostate, external genitalia and genital skin
E2 (aromatase enzyme complex) in muscle,
liver, kidney, brain, adipose tissue.
50% loosely bound to albumin (> 400 mg /L)
45% bound with high affinity to SHBG
1-2% to CBG
< % 4 is free
The normal level of SHBG is about 30-50%
lower in men than in women
 SHBG levels may be elevated in testosterone
deficient men.
 A change in the level of SHBG causes a
greater change in the free testosterone level
than in the free estradiol level.
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Effects of androgens
Sexual differentiation
 Spermatogenesis
 Development of secondary sexual organs
 Anabolic metabolism and gene regulation
 Male pattern behaviour
 Estradiol : sexual behavior and control
of LH secretion
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Targets for testosterone
Embryonic Wolffian structures,
spermatogonia, muscles,bone, kidney and brain
Targets for dihydrotestosterone
Prostate, external genitalia and the genital
skin
The kidney is a major target tissue of the
androgens : general enlargement of the kidney
Excretory metabolites : inactive
or less active
Oxidation at the 17-position in many
tissues, including the liver
 17 ketosteroids : androsterone and
etiocholanolone
 conjugated with glucuronide and sulfate
 Androstanediol
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Pathological States
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Primary hypogonadism
Genetic disorders : Klinefelter’s syndrome
Androgen receptor defects : Testicular
feminization syndrome
Inherited enzyme defects : 20,22-desmolase,
3ß-hydroxydehydrogenase,17α-hydroxylase
17,20 desmolase , 17-ketosteroid reductase
Failure of the pituitary/hypothalamus to
respond to low testosterone levels
In hypogonadism
Hypothalamus : Low GnRH ; low FSH,LH;
low E2 /testosterone
 Pituitary : High GnRH ; low FSH,LH ;
low E2 /testosterone
 Gonad : High GnRH ; high FSH,LH ;
low E2 /testosterone
 Hyperprolactinemia is associated with
diminished libido and impotence
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Hypergonadism
 Testicular hyperfunction : Testicular
tumors (often produce hCG and αfetoprotein)
 Hypothalamic/pituitary hyperactivity
usually from a tumor
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 Benign prostatic hypertrophy : extensive and
uncontrolled division of prostate cells
 Testosterone / dihydrotestosterone +
estradiol
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Erectile dysfunction may occur secondarily to
vascular problems associated with diabetes,
atherosclerosis
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Infertility