Sexual differentiation Flashcards
What effect does the secretion of T from the testis have?
Stimulates Wolffian duct formation and Mullerian inhibiting hormone (MIH) which causes the Mullerian duct to degenerate
=absence of uterus
MIH the same as and what is it?
(AMH) - Anti-Mullerian Hormone
Large molecular weight glycoprotein - part of TGF-beta super family
What is the jost hypothesis?
Secretion of androgens and AMH by fetal testis during critical stages of development accounts for tor the full range of sexually dimorphic urgogenital traits observed at birth.
What is maleness conferred by?
The SRY gene - small region at the tip of the Y chromosome
Is the embryo sexually differentiated at an early embryo?
No
Role of sertoli cells
(in the testis)
Germ support cells
- Secrete substances initiating meiosis and testicular fluid
- Concentrate testosterone locally with androgen binding protein
- Release AMH, prevent formation of ovarian duct
- Protect spermatids from the immune system
Role of Leydig cells
Androgen production
Events in the sex-neutral early embryo
Germ cells
XX
XO
XY
XX
XXY
Migrate to the gonadal region in early development
Cells survive in ovarian environment and produce follicles
Cells cannot produce follicles and germ cells die
Cells die in ovarian environment
Cells die in testicular environment
Klinefelter’s syndrome dies in testicular environment
Must be a ________ to ensure survival of female germ cell
X-linked dosage mechanism
- 2 Xs renders cell sensitive to cytotoxic effects of MIH?
Model for differentiation
Nuclear hormone receptor action
Testosterone acts with 5alpha DHT on a common receptor which directly binds to DNA
Cascade of development and Behavioural pathways
Early embryo - SRY switch - Testis develop - sex steroids produced
Testosterone
Multiple action on other genes
- Spermatogenesis
- Testicular descent
- Wolffian duct growth
- Gonadotrophin hormone regulation
- Differentiation of brain via oestrogen
5 alpha dihydrotestosterone
Multiple action on other genes
- External virilization
- ## Maturation at puberty
Klinefelters
Double dose of X plus Y chromosome
Small testis, low T production, limited breast development, no spermatozoa produced, scant body
XXY germ cells cannot survive in testicular environment
Testicular feminisation
Lack of androgen receptor
Body cannot perceive testosterone
Testicular oestrogen drives breast development
Voluptuous breasts - no T signal opposing oestrogen
No uterus present - MIH produced by testis
Testis do not descend
Vagina short and blind ending
XY testicular feminised indivudals raised as girls
Turner’s syndrome
[Female phenotype] - XO
Ovaries/streak gonads (no germ cells, no steroids)
Mullerian ducts present (no production of MIH - no testis present)
Wolffian ducts absent
No penis
Lack of germ cells = lack of sex steroid production - no breast development
Thickened neck
X-linked suppressor of SRY
Male karyotype
Underdeveloped female appearance
no testicular development
Ovaries develop but degenerate as streaks
Uterus and vagina normal
No ovaries = no sex steroids no pubic hair no breast development
