Biology of Sex Chromosomes and Hormones

Sex Determination

• Sex chromosomes are X and Y chromosomes
• Y chromosome is necessary and sufficient for production of testes
• Y chromosome contains the sex determining region that codes for SRY protein
• SRY protein binds DNA and acts as a transcription factor for many genes necessary for testicular differentiation, including MIS
• Spermatogonium cells (diploid cells) are of XY pattern
• Male sperm can be either X or Y pattern
• Oogonia cells (diploid cells) are of XX pattern
• Female ovum is X pattern

Gonadal Differentiation

• In genetic males, the medulla develops into a testis and the cortex regresses
• In genetic females, the cortex develops into an ovary and the medulla regresses
• Embryonic ovary does not secrete hormones
• Hormonal treatment of the mother has no effect on gonadal differentiation in humans
• Leydig and Sertoli cells appear and secrete testosterone and MIS in males

Testosterone

• Testosterone causes regression of Müllerian duct by apoptosis
• In boys, testosterone is secreted in bursts in the fetal period and again in the neonatal period

Puberty

• Thelarche: development of breast
• Pubarche: development of axillary and pubic hair
• Menarche: first menstrual period
• Adrenarche: increase in adrenal androgens (DHEA) at 8-10 in girls and 10-12 in boys

Leptin

• Leptin is the satiety-producing hormone secreted by fat cells, linking body weight and puberty
• Leptin treatment induces precocious puberty in immature female mice
• Leptin restores fertility in obese ob/ob mice that cannot make leptin

Menopause

• Definition: unresponsiveness of ovaries to gonadotropins with disappearance of sexual cycle with advancing age
• Cause: decline in the number of primordial follicles at the time of menopause (loss of ovarian function)
• During menopause, the ovaries no longer secrete progesterone and 17β-estradiol in appreciable quantities
• Estrogen is formed only in small amounts by androstenedione aromatization in peripheral tissues
• FSH secretion increases, and FSH plasma levels increase to high levels, and LH levels moderately high due to reduced negative feedback inhibition of estrogen and progesterone on the pituitary gland

Basal Body Temperature

• Rise starts 1-2 days after ovulation
• Temperature recording must be in the morning before getting out of bed
• The rise is probably due to an increase in progesterone secretion (progesterone is a thermogenic hormone)

Recording Ovulation Time and Fertile Period

• LH surge triggers ovulation
• Ovulation occurs ~ 9 hours after the peak LH surge
• The ovum lives ~ 72 hours after extrusion from the follicle
• BUT the ovum is fertilizable for a much shorter time than 72 hours
• Fertile period is 48 hours (2 days) before ovulation

Estrogens

• Estrogen sources: ovary
• Estradiol secretion rate in men: 50 μg/day
• Estrogen functions:
  • Ovarian follicle growth
  • Increase uterine tube (oviduct) motility
  • Cyclic change in endometrium (proliferation)
  • Make the cervix mucus thin and alkaline to promote survival of sperm
  • Cornified the vaginal epithelium (converted to hard tissue)
  • Increase uterine blood flow (necessary for secretory phase)
  • Promote more active excitation (contraction) of uterine smooth muscles (myometrium)
  • Increase sensitivity of uterine smooth muscle to oxytocin
  • Inhibit FSH secretion (-ve feedback)
  • In some circumstances, inhibit LH secretion (-ve feedback) and in other cases, increase LH secretion (+ve feedback)
  • Inhibit implantation of ovum when given in larger doses for 4-6 days (as morning-after contraceptives)
  • Promote breast enlargement at puberty in girls
  • Produce ductal growth in the breast
  • Responsible for the pigmentation of areolas at puberty and during pregnancy
  • Produce body changes characteristic of female
    • Enlarge breast (and uterus and vagina)
    • Narrow shoulders

Estrogen Receptors

• Nuclear receptors
• Act by gene transcription
• There are two types: ERα and ERβ
• ERα presents in uterus, kidney, liver, heart
• ERβ presents in ovaries, prostate, lung, GIT, bone marrow, and CNS
• Most effects of estrogen are genomic (production of mRNA)