Estrogens

Some Commonly Used Estrogens
ethinyl estradiol micronized estradiol estradiol cypionate estradiol valerate estropipate
mixed estrogenic agents diethylstilbestrol quinestrol chlorotrianisene methallenestril

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Physiological Effects:Estrogens

  •  Mechanism:Sequence
    1. sex hormone-binding globulin bind plasma estrogens (plasma)--forms complex
    2. complex dissociation followed by cell entry leading to intracellular estrogen receptor binding
      •   Estrogen Receptors:
        • steroid/thyroid receptor superfamily
        •  Location: mainly nuclear -- associated with stabilizing proteins
        • hormone + receptor interaction causes a conformational change with release of associated, stabilizing proteins (primarily hsp90)

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      •   Estrogen -- estrogen receptor complex
        • forms homodimers
        • homodimers buying to estrogen response elements (EREs) regulating transcription various genes
        • ERE -- receptor dimer interaction involves transcription element proteins
        • receptor complex: does not bind exclusively to gene promoter regions

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      • Genomic Effects:estrogen
        • consequence of proteins synthesized in response to gene(s) activation
        • also indirect genomic effects:
          •   paracrine effects of cytokines produced by regional cells under regulation by target cell proteins, induced by estrogen

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    • Membrane Estrogen Receptors:
      • Consequences of estrogen-activation of membrane receptors (no gene activation) include, e.g.:
        • rapid, granulosa cell calcium uptake
        • increased uterine blood flow

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  • Female Maturation:estrogen required for normal female maturation

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    • Stimulation:estrogen-
      •  stromal development
      •  ductal growth in the breast
      •  growth spurt/closing of the epiphyses of long bones (puberty)
      •  axillary & pubic hair; promote redistribution of body fat -- resulting in typical female body contours
      •  skin pigmentation -- particularly in the nipple region, areolae, and genital areas

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  • Endometrial Effects:estrogen
    •  Promotes endometrial lining development
    •   Continuous, excessive estrogen exposure endometrial hyperplasia (may cause abnormal bleeding)
    •   estrogen & progesterone coordination during normal menstrual cycle:
      • periodic bleeding
      • endometrial lining shedding

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  • Metabolic Effects:estrogen
    1. Maintenance of normal skin/blood vessel structure (in women)
    2. Decrease rate of bone resorption (parathyroid hormone antagonism)
    3. Promote intestinal absorption (decrease bowel motility)
    4. Hepatic effects -- metabolic and causes increased circulating concentrations of:
      • transcortin (CBG)
      • thyroxine-binding globulin (TBG)
      • sex hormone-binding globulin (SHBG)
      • renin substrate
      • transferrin
      • fibrinogen
      • These effects tend to increase the circulating concentrations of thyroxine,estrogen, testosterone, iron, copper, other compounds
    5. Plasma Lipid Effects:
      • increased in high-density lipoproteins
      • slight decrease in low-density lipoproteins
      • decreased cholesterol
      • increase plasma triglycerides
        • increased triglycerides synthesis
        • decreased lipid oxidation ketones

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  • Blood Coagulation:Estrogen
    • Estrogen: causes enhancement of blood coagulation
      • increased circulating factors II, VII, IX, X. {note hepatic effects}
      • decreased antithrombin III
      • increased plasminogen concentration
      • decreased platelet adhesiveness

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  • Miscellaneous Effects: Estrogen
    1. induce progesterone receptor synthesis
    2. affect human libido
    3. promote renal Na/water retention
    4. influence sympathetic nervous system-mediated smooth muscle tone

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Primary Reference: Goldfien, A., The Gonadal Hormones and Inhibitors, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 653-680.