Estrogens and Progestins

Estrogens and Progestins

1. Definition & overview

• Estrogens are substances that induce estrus in spayed (ovariectomized) animals; the female sex hormones responsible for pubertal development, cyclical preparation of the reproductive tract, and major actions on mineral, carbohydrate, protein and lipid metabolism (G&G 14e Ch.48, p.959; KDT 8e Ch.22, p.330).
• Progestins ("favouring pregnancy") convert an estrogen-primed proliferative endometrium to secretory and maintain pregnancy in animals spayed after conception; compounds with progesterone-like biological activity are termed progestins, progestational agents, progestagens or gestagens (KDT 8e Ch.22, p.340; G&G 14e Ch.48, p.969).
• Both act via well-characterized nuclear receptors that mediate biological effects in liganded and, for the estrogen receptor, partly unliganded states (G&G 14e Ch.48, p.959).
• The two most common therapeutic settings are contraception and menopausal hormone therapy (MHT/HRT); the specific agents and doses differ substantially between the two — e.g. combined oral contraceptives use 20–35 µg/day ethinylestradiol, whereas MHT uses conjugated estrogens ≈0.625 mg/day (potency-equivalent to only 5–10 µg ethinylestradiol) (G&G 14e Ch.48, pp.959, 982).
• Antiestrogens (clomiphene) treat anovulatory infertility; antiprogestins/PRMs (mifepristone, ulipristal) are used for medical abortion and emergency contraception (G&G 14e Ch.48, p.959).

Historical anchors

• Ovarian hormonal control established by Knauer (1900); Allen & Doisy (1923) devised the rat vaginal-smear bioassay; estradiol crystallized by Butenandt & Doisy (1929) (G&G 14e Ch.48, p.960; KDT 8e Ch.22, p.330).
• Corpus luteum hormone isolated 1933 (Corner & Allen, "progestin"; Europeans "luteo-sterone"); name progesterone agreed 1935. Marker synthesized progesterone from plant diosgenin (1940s); Djerassi synthesized norethindrone (Syntex) and Colton norethynodrel (Searle) in the early 1950s — the first orally active progestins (G&G 14e Ch.48, p.969).
• Jensen (early 1960s) demonstrated intracellular estrogen receptors — the first steroid/thyroid-superfamily receptor; ERβ identified 1996 (renaming the earlier receptor ERα) (G&G 14e Ch.48, p.960).