Download Sexual Differentiation

Sexual Differentiation
Male differentiation – from chromosomal to
gonadal sex
• Step 1: zygote has XY genotype;Y chromosome
possesses only a few functional genes, but does
have a gene called SRY that codes for testisdetermining factor.
• Step 2: The fetal indifferent gonad has the
potential to differentiate either as a testis or an
ovary; the activity of SRY causes the medullary
portion of the gonad to differentiate as a testis
and the cortical portion to degenerate.
Y-chromosomal anomalies
• OY – lethal
• XYY – “supermale” – taller than average,
reduced fertility – possible behavioral
issues
• XXY – Klinefelter’s S. – male body pattern
at birth – hypogonadism – weakly
masculinizing puberty – infertility, unless
the syndrome occurs as a mosaic
condition.
The embryonic reproductive system is
bipotential
The primitive gonad is embedded in an embryonic kidney, the
mesonephros. In response to the SRY gene, germ cells migrate into the
tubules of the mesonephros, while the cortical portion degenerates.
From gonadal
sex to
concordant
internal genitalia
Of the two tube
systems associated
with the gonads,
the Wolffian system
can give rise to the
male gland and
duct system; the
Mullerian system
can give rise to the
female uterus,
Fallopian tubes and
inner vagina.
Control of internal genital differentiation by
the testis involves two separate secretions
• Under the stimulation of chorionic
gonadotropin from the placenta, the
testis functions as an endocrine organ,
secreting
– Testosterone, which promotes the growth
and differentiation of the Wolffian system into
the epididymis, vas deferens, seminal
vesicles, ejaculatory duct and prostate.
– Mullerian inhibiting substance, which
abolishes the Mullerian system
Differentiation of the external genitalia as
male is driven by dihydrotestosterone
Target tissues are responsible for converting
testosterone to dihydrotestosterone
• Conversion of testosterone to
dihydrotestosterone is catalyzed by 5alpha reductase. If this enzyme is
deficient, external genitalia will fail to
masculinize before birth, causing one form
of pseudohermaphroditism.
Other prenatal effects of testosterone
• Establishes non-cyclic release of gonadotropin
at puberty
• Diminishes female-specific behavior and/or
promotes male-specific behavior. In animals in
which fetuses share a single placenta, a male
fetus can masculinize adjacent female fetuses
• Establishes male-typical brain morphology and
spinal reflex pathways involved in male genital
reflexes.
Masculinizing Puberty
• Primary event: increased secretion of LH
and FSH (primarily during nighttime) –
leads to:
– Testicular growth to mature size
– Initiation of spermatogenesis
– Steep rise in testosterone secretion
Pubertal and postpubertal effects of testosterone
and its derivatives (dihydrotestosterone, 5-alpha
androstanediol)
• Growth of penis and male gland-duct system to
final size
• Anabolic effect contributes to pubertal growth
spurt – which ends when epiphyses close over.
• ♂ pattern of body hair and pubic hair
• Maintains spinal circuits involved in erection and
ejaculation
• Increases hematocrit
• Sustains male behavior and sexual interest
• Necessary for continued spermatogenesis
Origin and fate of testosterone
Leydig Cells
Brain
(aromatase;
converts to
estradiol)
Sertoli cells
(aromatase)
Other target tissues
(5α reductase converts
to dihydroT)
Estradiol
– some
appears
in blood
5 α androstanediol
Facial, pubic, axillary hair
17-keto steroids (urine) 30% from testis;
70% from adrenal cortex
Adrenal cortex
Regulation of testicular function
hypothalamus
Gnrh
testosterone
Ant. pituitary
inhibin
FSH
LH
Testis
Sertoli cells
Spermatogenesis
Leydig cells
testosterone
Male sexual response: erection
• Parasympathetic input to penile arterioles
causes release of NO
• Arterioles dilate, filling venous sinuses
(corpora cavernosa and corpus
spongiosum) with blood under arterial
pressure; outflow veins are compressed.
• Erection can be antagonized by α
adrenergic input.
Let’s get to the point – some
anatomy
In the flaccid penis (and
clitoris), cavernous
arteries are constricted
and the small amount of
volume flow into the
sinuses easily drains into
the veins.
Erection is the result of
dilation of the cavernous
arteries and trabecular
smooth muscle. As the
sinuses fill with blood
under arterial pressure,
they compress the
vessels in the venular
plexus, making outflow
more difficult.
Male sexual response: ejaculation
• Primary driver is burst of sympathetic
output
• 1st stage: Gland-duct system contracts:
emission of semen into urethra
• 2nd stage: urethra contracts rhythmically,
causing ejaculation