Lecture 2: Male Sexual Development Flashcards
Genotypic sex
The genotypic sex involves the Y chromosome (49, XXXXY genotype is male).
Gonadal Sex
While the gonadal sex: SRY gene encodes testis determining factor (TDF) which is a transcription factor. When the SRY gene is present, indifferent gonads becomes testes AND germ cells develop in spermatogonia (6-8 weeks of gestation)
The phenotypic sex involves
the hormones produced by the gonads that determine the phenotypic sex. This includes development of accessory sex organs, external genitalia (penis, scrotum, urethra) that require the presence of DHT as well as the secondary sex characteristics.
XX Male
SRY gene, which contains the TDF region translocates from the Y chromosome to the X chromosome during male meiosis. The ovum will develop into a male. Crossing over events between normal X and Y chromosome of the father can generate an X-chromatid that contains a substantial portion of the TDF and a Y chromosome that lacks the SRY region (TDF).
XX Male again
If a sperm cell bearing an X-chromosome with a transloctaed TDF feritizes an ovum, the result is a male with a 46, XX karyotype because one of the X chromosomes contains the TDF.
Differentiation of the testis
o When the gonad is still indifferent, it is closely associated with the mesonephros (Wolfian duct) and the excretory duct.
Mesonephros develops into
epididymis
Wolffian duct develops into
Wolfian duct develops in vas deferens, seminal vesicles and ejaculatory duct.
Androgens from Leydig cells promote this and prostate development
Mullerian ducts degenerate (because they would have developed into fimbriae in females). This is controlled anti-Mullerian hormone by from the Sertoli cells
Embryonic gonad affects the development of the INTERNAL GENITALIA
Androgens produced by Leydig cells promote the development of wolffian ducts and its derived structures listed above.
REQUIRES TESTOSTERONE, not DHT
Homologous Regions of Male and Female EXTERNAL GENITALIA
o No testosterone available, the undifferentiated external genitalia is female by default.
o TESTOSTERONE, after conversion to DHT stimulates formation of male external genitalia from the undifferentiated structures.
Hypothalamic-Pituitary-Gonadal Axis
o Regulates spermatogenesis and androgen production
o GnRH stimulation is pulsatile (if it were constant it would prevent LH and FSH release by downregulating receptors…used to treat prostate cancer by lowering Testosterone production). Since GnRH release is pulsatile, LH and FSH release are pulsatile.
o Products of testes negatively feedback on the hypothalamus and anterior pituitary
o GnRH binds GPCR, activating phospholipase C that ultimately causes calcium release, DAG production and protein kinase C activation
H-P-G Axis in the prenatal stage
Leydig cells in the testes make the androgens (sex-steroids). They are the dominant cell types in the testes (Increase in Leydig cells is dependent on maternal hCG in early development and on LH in later development).
H-P-G Axis prior to puberty
o less pulse of GnRH, therefore less LH/ FSH release
o lots of androgens around so they negatively feedback on the hypothalamus and anterior pituitary
o spermatogonia exist in diploid, undifferentiated form in the basal compartment of the testes
H-P-G Axis at Puberty
increased frequency and amplitude of GnRH pulses
• H-P-G axis not as sensitive to negative feedback of testosterone (an androgen) but the gonadotrophs become more sensitive to GnRH which causes increases in LH and FSH production
• Testosterone increases and spermatogenesis begins and you also get the rest of the signs of puberty
Kallman Dz:
lack of the ant pit hormones LH & FSH; patients never enter puberty and hv no sense of smell because the mutation prevents the sensory neurons from extending their axons into the olfactory bulb. GnRH secreting cells walk along these into the brain and then into hypothalamus
The hypothalamic-pituitary-testicular axis
o GnRH causes the gonadotrophs to make and release FSH and LH. LH binds to Leydig cell receptors, upregulating testosterone. FSH binds binds to Sertoli cells upregulating transcription of ABP, growth factors and inhibin.
o Negative Feedback on this axis: Testosterone inhibits pulsatile release of GnRH and LH. And inhibin inhibits the release of FSH by the gonadotrophs in the ant pit.