Updated: 6/9/2021

Estrogen and Progesterone

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Overview
 

Introduction
  • Female hormones
    • in follicular phase of menstrual cycle, follicle synthesizes estrogens
      • major product is 17β-estradiol
    • in luteal phase of menstrual cycle, corpus luteum synthesizes progesterone and estrogen
      • major product is progesterone
Estrogen
 

estrogen production

  • Sources of estrogens
    • ovary (17β-estradiol)
    • placenta (estriol)
    • blood (aromatization)
  • Estrogens biosynthesis
    • two-cell, two-gonadotropin model
      • 17β-estradiol synthesis requires granulosa cells and theca cells
        • theca cells do not express aromatase
          • aromatase catalyzes conversion of androstenedione to 17β-estradiol
      • biosynthetic pathway
        • LH acts on theca cells
          • increases activity of cholesterol desmolase
            • increases synthesis/secretion of androstenedione
            • androstenedione freely diffuses from theca cells to granulosa cells
        •  FSH acts on granulosa cells
          • increases activity of aromatase
            • increases synthesis/secretion of 17β-estradiol
  • Estrogens potency
    • 17β-estradiol > estrone > estriol
  • Estrogen receptor
    • estrogen receptor (ER) functions as a homodimer and resides in cell cytoplasm
    • estrogen-ER complex translocates to cell nucleus, interacts with steroid response elements on chromatin, and rapidly induces transcription of target genes
  • Function of estrogens
    • at puberty, functions in development of female sex characteristics
      • genitalia, breasts, and female fat distribution
    • functions in proliferation and development of ovarian granulosa cells of follicles
    • functions in maturation and maintenance of uterus
      • proliferates endometrium of uterus
      • lowers uterine threshold to contractile stimuli
        • increases myometrial excitability
    • upregulates estrogen, progesterone, and LH receptors
    • negatively feeds back on anterior pituitary in follicular phase of menstrual cycle 
      • ↓ FSH and ↓ LH
    • positively feeds back on anterior pituitary at midcycle in response to LH surge
      • ↑ FSH and ↑ LH
    • stimulates prolactin secretion
      • blocks action of prolactin on breasts
    • upregulates transport proteins
      • in blood plasma, estrogens are mostly bound to carrier proteins
        • e.g., albumin and sex hormone-binding globulin (SHBG)
    • upregulates HDL cholesterol and downregulates LDL cholesterol
  • Notes
    • pregnancy
      • 50-fold ↑ in 17β-estradiol and estrone
      • 1,000-fold ↑ in estriol
        • increase in estriol levels is an indicator of well-being of fetus
Progesterone
  • Sources of progesterone
    • corpus luteum, placenta, adrenal cortex, and testes
  • Function of progesterone
    • stimulates endometrial glandular secretions
    • stimulates development of spiral arteries
    • maintains pregnancy
    • raises uterine threshold to contractile stimuli during pregnancy
      • decreases myometrial excitability
    • relaxes uterine smooth muscle
      • prevents contractions
    • produces thick cervical mucus that inhibits sperm entry into uterus
    • increases basal body temperature
      • increases hypothalamic temperature set-point
    • negatively feeds back on anterior pituitary in luteal phase of menstrual cycle
      • ↓ FSH and ↓ LH
    • downregulates estrogen receptors
  • Notes
    • increase in biosynthesis of progesterone is characteristic of mid cycle or ovulation
    • "PROGESTerone is PRO-GESTation"
Estrogen and Progesterone in Pregnancy
  • Overview
    • estriol is major estrogen in pregnancy
  • Maternal-placental-fetal unit
    • elevated levels of estrogens and progesterone are necessary for maintaining pregnancy
    • corpus luteum is not adequate to generate very high hormone levels
    • placenta emerges as major source of estrogens and progesterone
    • placenta is an imperfect endocrine organ
      • placenta cannot synthesize sufficient cholesterol
        • cholesterol is a precursor for hormone synthesis
      • placenta lacks necessary enzymes for estrogen synthesis
    • maternal-placental-fetal unit overcomes shortcomings of placenta to very high hormones levels
  • Progesterone synthesis
    • mother provides cholesterol (LDL particles) to placenta
    • placenta converts cholesterol to pregnenolone then to progesterone
    • placenta provides high progesterone levels to mother
  • Estriol synthesis
    • mother provides cholesterol (LDL particles) to placenta
    • placenta converts cholesterol to pregnenolone to progesterone
    • placenta provides high progesterone levels to fetus
    • fetal adrenal cortex converts progesterone to DHEA-sulfate
    • fetal liver hydroxylates DHEA-sulfate to 16-OH DHEA-sulfate
    • fetus provides high levels of 16-OH DHEA-sulfate to placenta
    • placenta converts 16-OH DHEA-sulfate to estriol
    • placenta provides high estriol levels to mother

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