Updated: 6/9/2021

Estrogen and Progesterone

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  • 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 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
  • 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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(M1.RP.13.3) A 19-year-old female complains of abnormal facial hair growth. This has been very stressful for her, especially in the setting of not being happy with her weight. Upon further questioning you learn she has a history of type 2 diabetes mellitus. Her height is 61 inches, and weight is 185 pounds (84 kg). Physical examination is notable for facial hair above her superior lip and velvety, greyish thickened hyperpigmented skin in the posterior neck. Patient is started on a hormonal oral contraceptive. Which of the following is a property of the endometrial protective hormone found in this oral contraceptive?

QID: 100503

Decreases thyroid binding globulin



Thickens cervical mucus



Enhances tubal motility



Decreases LDL



Increases bone fractures



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