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 testis-determining 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 5-alpha 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 Sertoli cells (aromatase)

Estradiol – some appears in blood

Other target tissues (5α reductase converts to dihydroT)

Brain (aromatase; converts to estradiol)

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

Ant. pituitary

Testis

Sertoli cells Leydig cells

Spermatogenesis testosterone

Gnrh

LHFSH

testosterone

inhibin

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