Testosterone and Chromosomal Sex Flashcards
What actions does testosterone have in the male?
- Reaches peak in males between 15-30
- Brain → helps concentration and possibly memory
- Libido → inreases sex drive
- Voice → deepens voice at puberty
- Muscles → increases lean muscle mass
- Fat → cuts down body fat
- Hair → stimulates growth on face, chest, genitals and underarms
- Organs → triggers normal development of male sex organs (T = wolffian duct stimulation, spermatogenesis. DHT = external sex organ).
- Bone → increases bone density and growth
• Jost Hypothesis:
• The secretion of androgens and AMH by fetal testis during critical stages of development accounts for the full range of sexually dimorphic urogenital traits observed at birth
− AMH mullerian duct degeneration
− Testosterone stimulates wolffian duct formation
What are the cell types in the adult testis?
• Sertoli cells → within the spermatogenic tubule.
− Secrete substances initiating meiosis
− Secrete testicular fluid
− Concentrate testosterone locally with androgen binding protein
− Release AMH
− Protect spermatids from the immune system
• Leydig cells → in the interstitial space between the tubules
− Secrete testosterone (converted to DHT in the sertoli cell)
• Myoid cells → in the interstitial space between the tubules
− Squeezeing action that moves sperm
What are the events in the sex neutral early embryo?
- At the genital ridge, SRY gene is expressed in male cells
- This stimulates sertoli cell differention, which provide support for developing germ cells and cause mullerian duct regression.
- This signals to activate steroid producing leydig cells
- Steroid action on distal targets throughout the genome causes wolffian duct differentiation, male external genitalia differentiation and growth and testes descent.
What is the effect of germ cells with different genotypes in the gonad?
− XX cells survive in an ovarian environment and produce follicles
− XO cells cannot produce follicles, and germ cells die → there must be an X linked dosage mechanism to ensure survival. In most somatic cells, one X is inactivated, but in the ovary you need both
− XY cells die in the ovarian environment (again, lacks double dose)
− XX cells die in the testicular environment
− XXY (Klinefelters) also dies in the testicular environment → perhaps XX renders the cell sensitive to the cytotoxic effects of MIH.
Explain the phenotype of an XY castrate
- Scant pubic hair – believed the adrenals are a low level source of androgen, which is why females have pubic hair in the absence of testosterone
- Small penis – as development is dependent on exposure to androgens
- Lack of androgen effect on long bone growth and continued growth
- Studies have also shown that castration in early life has an effect on the life span of males – study of Korean eunuchs lived longer
Explain the phenotype of an XXY Klinefelters
- Small testis – low testosterone production
- Some breast development
- NO sperm produced – XXY cells cant survive the testicular environment
- Scant body hair
- Less interest in sex
- Intelligance normal although reading and speech difficulties more common
- Often taller
Explain the phenotype of an XY - X linked suppressor of SRY (Swyer Sydrome)
- Male karyotype, but underdeveloped female appearance
- No testicular development
- Ovaries develop, but are streak gonads. Often removed due to risk of tumours
- Uterus normal (without AMH, mullerian ducts develop into mormal uterus)
- Vagina are normal (lack of testosterone, so not DHT, so no male external genitalia)
- No ovaries = no sex steroids, therefore no pubic hair, breast development and tall stature
Explain the phenotype of an XY - Testicular feminisation
- Lack of androgen receptor, body cannot perceive testosterone
- Testicular estrogen drives breast development
- Voluptuous breasts as no testosterone capable of opposing signal
- No uterus, as MIH produced
- Testes do not descent, as this is dependent on testosterone. Remain intra-abdominal
- Vagina is short and blind ending
- Raised as girls and identify as adults as women
- Interesting, as in the last lecture we learned that brain sex is determined by aromatisaion of testosterone in the brain → so even without AR, the brain of these individuals should be masculinized, and they should behave as males
- Clue that in humans, brain sex and gender identity is not so strongly determined by aromatisaiton, but more do to with social interactions.
Describe the phenotype of an XO - Turners
- Streak gonads, because you need XX for a functional ovary
- Mullerian ducts present (no production of MIH)
- Wolffian ducts absent
- No penis
- Lack of gem cells means lack of sex steroid production
- No breast development
- Thickened neck
Describe the Guevedoce phenotype
- 1970s, Dr Julianne Imperato visited a village in the Dominican Republic
- Girls turn into men at puberty
- Psudohermaphrodites
- Raised as girls
- At puberty, testosterone levels rise to sufficient levels to virilize the body
- Testes descend, penis develops and grows
- Controversy other whether such children suffer from gender identity issues
- Have a 5-a reductase deficiency (cannot synthesise DHT)
What is the danger of female exposure to androgen during pregnancy?
- Child genetically female, but they may be externally virilised or develop abnormal male sexual characteristics
- Can also have:
- Enlarged genitals
- Premature growth of pubic hair
- Increased self-stimulation
- Aggressive behavior
