Cells of the testis
• Spermatogonia• Leydig (interstycial) cells:
– Influence of LH• testosterone
• Sertoli cells:– Optimális medium for the
differentiation of a spermiums– FSH, LH stimulate
spermatogenézist• The maturing germ cells
and spermatids (left arrow) • Leydig cells (right arrow)
are shown at higher magnification
Testosteron & DHT
Biosynthesis of testosteron
C
CH3
O
HO O
C O
CH3
O
C O
CH3
OH
C
CH3
O
HO
OH
HO
O
O
O
O
OH
HO
OH
17--hidroxiláz
C17,20-liáz
17--hidroxiszteroid dehidrogenáz
Pregnenolon
17--hidroxi-pregnenolon
Dehidroepiandroszteron
5-Androszténdiol Tesztoszteron
Androszténdion
17--hidroxi-progeszteron
Progeszteron
Biosynthsis oftestosteron
Mechanism of the action of testosteron
androgen receptorbinds testosterone directly or its active metabolite 5-dihydrotestosterone (DHT). dissociation of heat shock proteins (hsp)the receptor enters the nucleus steroid hormone bindingeither in the cytoplasm or in the nucleus, the androgen receptor binds as dimers to specific DNA elements present as enhancers in upstream promoter sequences of androgen target genes.
RNA-polymerase II [RNA-Pol II],TATA box binding protein [TBP], TBP associating factors [TAF's], general transcription factors [GTF's])triggers mRNA synthesis consequently protein synthesisresults in an androgen response.
Hormons of testis
• 50-100 g DHT/day• Periferial testosteron + DHT conversion
• 17-estradiol (E2)
• Leydig-, Sertoli-cells• FSH regulation?• Testosteron:
– dominant: prenatál period, puberty
– 5 mg/day adult men
– After birth: only androsterone
[testosteron] is lowered by the years
• Sex Hormon Binding Protein (SHBP) vagy (Testosterone-Estrogen Binding Protein (TEBP)
• 97-99 % testosteron / SHBP + albumin
• SHBP– liver– Estrogen elevates its level– testoszterone decreases
Testosteron + DHT
• Sexual differenciátion• Spermatogenesis• Secundary sexual characters• Anabolic effects, gén-regulation
• Benign hypertrophy of prostatse • – 5hydroxylase inhibitiors• Lack of Testosteron biosyntesis
– hipogonadizmus– 5hydroxilase defective receptors
The role of testosteron / DHT receptor
• Testicular feminization syndrome
Note the absence of lumens and presence of only sertoli cells in the seminiferous
tubules. Numerous Leydig cells are seen. Leydig cells
in testicular feminization syndrome often lack Reinke’s crystalloids
Testosteron metabolism
• Oxydation at C17 position
• Reduction at C3 , double bond
Tesztoszteron
OH
O
Ovarium: steroid hormon synthesis
– Theca interna
– Stratum granulosum
Aromatáz
Androszténdion
17-HSDH
Petefészek -Stratum granulosum
Ösztron Ösztradiol
Tesztoszteron
Petefészek - Theca Interna
Koleszterin
Pregnenolon
Progeszteron
Oldallánc hasítás
3-HSDH
17-OH-progeszteron Androszténdion
17-OH-pregnenolon DHEA
17-OH-áz 17,20-liáz
Petefészek - Theca interna
Biosynthesis of steroid hormons: ovarium - granulosa cells
Petefészek -Stratum granulosum
Ösztradiol (E2)
Tesztoszteron
Androszténdion
OH
HO
Aromatáz
HO
O
Ösztron (E1)
Ösztriol
HO
HO
OH
Koleszterin
HO
HO
C
CH3
O
C
CH3
O
O
Koleszterin
Pregnenolon
Progeszteron
• Folliculus – estrogen– the endometrium to become thicker and more richly supplied with blood vessels and glands
• rising level of LH causes the developing egg within the follicle to complete the first meiotic division (meiosis I), forming a secondary oocyte.
• ~ 2 weeks, there is a sudden surge in the production of LH. • LH triggers ovulation• the release of the secondary oocyte into the fallopian tube.
• Under the continued influence of LH, the now-empty follicle develops into a corpus luteum
• Stimulated by LH, the corpus luteum secretes progesterone which – continues the preparation of the endometrium for a possible pregnancy – inhibits the contraction of the uterus – inhibits the development of a new follicle
• If fertilization does not occur (which is usually the case), – the rising level of progesterone inhibits the release of GnRH which, in turn, inhibits further
production of progesterone.• As the progesterone level drops,
– the corpus luteum begins to degenerate; – the endometrium begins to break down, its cells committing programmed cell death (apoptosis); – the inhibition of uterine contraction is lifted, and – the bleeding and cramps of menstruation begin.
Placenta – trophoblasts – steroid hormon syntesis
HO
HO
C
CH3
O
C
CH3
O
O
Koleszterin
Pregnenolon
Progeszteron
Aromatáz
Androszténdion
17-HSDH
Ösztron Ösztradiol
Tesztoszteron
MellékvesekéregDHEA-SDHEA Androsztándiol
3-HSDH
Synthetic agonists, antagonists influence the conception and tumor proliferation
CH3
CH2
CC
CH3CH2
HO
OH
Dietilstilbestrol
OH
C CH
CH3O
Mestranol
C
C
Cl
OCH2CH2N
C2H5
C2H5
Clomifén citrát
OH
C CH
HO
17 Ethynyl estradiol
Clomifene (INN) or clomiphene (USAN and former BAN) or Clomid or Clomifert
is a selective estrogen receptor modulator (SERM), used mainly in female infertility due to
anovulation (e.g. due to polycystic ovary syndrome). In some countries, it is also registered
for use in men. Clomiphene citrate is marketed under various trade names including Clomid,
Serophene, Milophene, etc.
Clomifene acts by inhibiting the action of estrogen on the gonadotrope cells in the anterior pituitary gland.
In response to low estrogen levels, follicle-stimulating hormone
(FSH) release is increased, leading to a higher rate of ovulation and hence pregnancy.
Clomifene can lead to multiple ovulation, and hence increasing the chance of twins.
In comparison to purified FSH, the rate of ovarian hyperstimulation syndrome is low.
There may be an increased risk of ovarian cancer and weight gain.
Top Related