7

• Progesterone


  Steroid hormone, intermediate in steroid hormone biosynthesis in all tissues that secret steroid hormones (gonads, adrenal gland)
• Progesterone secretion

  1. Secreted in large amounts by Corpus luteum; placenta

  2. Secreted in small amounts by follicles, testes, and adrenal gland

  
• Progesterone binding to plasma proteins

  98% bound to plasma protein (80% to albumin & 18% to Transcortin), 2% is free

  
• Progesterone half-life

  Short due to liver metabolism
• Progesterone metabolism

  1. 90% metabolized by liver to pregnanediol (inactive) that conjugate to glucuronic acid and excreted in urine

  2. Rate of progesterone synthesis is extremely rapid to overcome such high excretion rate

  
• Plasma level of progesterone in men: 0.3ng/ml

  
• Plasma level of progesterone in women

  • In early follicular phase: 0.9ng/ml (by granulosa cells of follicle)
  • In late follicular phase: begins to increase
  • In luteal phase: 18ng/ml (by the remaining theca cells)

  
• Corpus theca cells


  Contain GPCR-cAMP operated receptors, cAMP causes increase in StAR synthesis and hence increase entry of cholesterol into mitochondria
• Targets of progesterone


  • Uterus
  • Breast
  • Brain

  
• Effects of progesterone on uterus

  • Decrease myometrial excitability (anti-estrogen)
  • Decrease myometrial sensitivity to oxytocin
  • Decrease estrogen receptors in endometrium
  • Increase the rate of conversion of 17β-estradiol to less active estrogens (Estrone and Estriol)

  
• Effects of progesterone on breast

  • Stimulate the development of lobules and alveoli
  • Induce differentiation of ductal tissue that prepared by estrogen
  • Support the secretory function of breast during lactation

  
• Progesterone is not a precursor for aldosterone biosynthesis

  
• Progesterone is 98% bound to plasma proteins

  
• The rate of progesterone biodegradation is about 90%

  
• The rate of progesterone biosynthesis is extremely high during luteal phase, not follicular phase

  
• Progesterone is mainly produced by theca cells of corpus luteum, not follicles

  
• Effects of progesterone on uterus

  • Decreasing the myometrium excitability
  • Decreasing estrogen receptors in myometrium
  • Increasing the rate of estrone formation
  • Increasing the secretory rate of endometrial glands

  
• Effects of progesterone on brain

  • Negative feedback on LH secretion (directly on pituitary gland and indirectly on hypothalamus)
  • Thermogenic effect (rise basal body temp. during ovulation)
  • Stimulate respiration and thus decrease PCO2 when start released during luteal phase compare to PCO2 in men

  
• Effects of progesterone on kidney


  • Produce natriuresis by blocking the action of aldosterone on the kidney

  
• Progesterone has no anabolic effect on muscle

  
• The feedback effects of progesterone are complex and are exerted at both the hypothalamic and the pituitary gland levels

  
• The feedback effects of progesterone potentiate the inhibitory effect of estrogens on ovulation

  
• The feedback effects of progesterone are not inhibited by large doses of progesterone

  
• The feedback effects of progesterone are present during follicular phase

  
• Relaxin

  Polypeptide hormone
• Sites of relaxin production

  • Corpus luteum
  • Uterus
  • Placenta
  • Mammary glands
  • Prostate
• Relaxin is not produced by hepatocytes

  
• Effects of relaxin in pregnant women

  • Facilitate delivery by relaxing the pubic symphysis and other pelvic joints, softening and dilating the uterine cervix, inhibiting uterine contractions
  • Play role in development of mammary glands

  
• Relaxin has unknown function in nonpregnant women
• Relaxin is found in semen and aids sperm motility and penetration of the ovum
• Hormonal changes during the menstrual cycle

  1. During early follicular phase: Inhibin is low, FSH modestly elevated – fostering follicle growth

  2. During late follicular phase (36-48hr before ovulation): Estrogen is elevated – produce –ve feedback on FSH and +ve feedback on LH (producing LH surge & ovulation begins)

  3. Ovulation occurs 9hr after LH surge (strong GnRH secretion which also cause peak secretion of FSH despite small rise in inhibin B)

  4. During luteal phase: FSH and LH secretions are low (-ve feedback effects of estrogen, progesterone and inhibin)

  5. Moderate-constant levels of plasma estrogen (before ovulation) -ve feedback on LH secretion, elevated estrogen level (at ovulation) +ve feedback on LH secretion