gonad hormones : male prof.dr.gülden burçak 2011-2012
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Gonad Hormones : Gonad Hormones : MaleMale
Prof.Dr.Gülden BurçakProf.Dr.Gülden Burçak
2011-20122011-2012
TestisTestis male sex hormones male sex hormones male germ cellsmale germ cells
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
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
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
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 (steroidogenic acute regulatory protein (StAR)acute regulatory protein (StAR)
LH (cAMP) (chronic) : steroidogenic LH (cAMP) (chronic) : steroidogenic enzyme synthesisenzyme synthesis
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
5α-reductase,type I : liver
Type II : reproductive tissues and peripheral targets
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.
Effects of androgens
Sexual differentiation Spermatogenesis Development of secondary sexual
organs Anabolic metabolism and gene
regulation Male pattern behaviourEstradiol : sexual behavior and control
of LH secretion
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
Pathological States 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 hypogonadismIn hypogonadism
Hypothalamus : Low GnRH ; low Hypothalamus : Low GnRH ; low FSH,LH; low E2 /testosteroneFSH,LH; low E2 /testosterone
Pituitary : High GnRH ; low FSH,LH ; Pituitary : High GnRH ; low FSH,LH ; low E2 /testosterone low E2 /testosterone
Gonad : High GnRH ; high FSH,LH ; Gonad : High GnRH ; high FSH,LH ;
low E2 /testosteronelow E2 /testosterone Hyperprolactinemia is associated Hyperprolactinemia is associated
with diminished libido and impotencewith diminished libido and impotence
Hypergonadism Testicular hyperfunction : Testicular
tumors (often produce hCG and α-fetoprotein)
Hypothalamic/pituitary hyperactivity usually from a tumor
Benign prostatic hypertrophy : extensive and uncontrolled division of prostate cells
Testosterone / dihydrotestosterone + estradiol
Erectile dysfunction may occur secondarily to vascular problems associated with diabetes, atherosclerosis
Infertility