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.