6

• Estrogens


  17βestradiol, estrone and estriol
• Estrogens


  • Steroid hormones
• Estrogen biosynthesis

  1. Testosterone converted to estradiol by aromatase in granulosa cells

  2. Androstenedione converted to estrone in fat, liver, muscle and brain

  3. Androstenedione diffuses into granulosa cells and converted to estradiol by aromatase

  4. FSH activates aromatase enzyme in granulosa cells

  5. Mature granulosa cells acquire LH receptors to stimulate estradiol production

  
• Estradiol binding to plasma proteins

  98% bound (60% to albumin, 38% to gonadal steroid-binding globulin), 2% free circulating
• Estrogen metabolism and excretion

  1. Estradiol, estrone, and estriol metabolized by glucuronide and sulfate conjugation in liver

  2. Metabolites excreted in urine

  3. Appreciable amounts secreted in bile and reabsorbed (enterohepatic circulation)

  
• Estradiol secretion rates


  • Early follicular phase: 36 μg/day
  • Just before ovulation: 380 μg/day
  • Midluteal phase: 250 μg/day
  • After menopause: low levels
• Estradiol secretion rate in men

  • 50 μg/day
• Estrogen functions


  • Ovarian follicle growth
  • Increase uterine tube motility
  • Cyclic change in endometrium (proliferation)
  • Thin and alkaline cervical mucus to promote sperm survival
  • Cornify vaginal epithelium
  • Increase uterine blood flow
  • Promote uterine smooth muscle contraction
  • Increase uterine sensitivity to oxytocin
  • Inhibit FSH secretion (negative feedback)
  • Inhibit or increase LH secretion (negative or positive feedback)
  • Inhibit implantation when used as emergency contraceptive
  • Promote breast development at puberty
  • Produce ductal growth in breast
  • Responsible for areolar pigmentation
  • Produce female body changes (breast, shoulder, hip, fat distribution, voice, hair)

  
• Fat distribution in breast and buttocks also seen in castrated males
• Growth of pubic and axillary hair in male and female is due primarily to androgens rather than estrogens
• Estrogen receptors


  • Nuclear receptors that form homodimers and bind DNA to regulate gene transcription
  • ERα present in uterus, kidney, liver, heart
  • ERβ present in ovaries, prostate, lung, GIT, bone marrow, CNS

  
• Most effects of estrogen are genomic (production of mRNA) but non-genomic effects are possible to explain rapid effects on neuronal discharge and negative feedback on FSH