Effect of 20α-dihydroxyprogesterone on the estrogen-induced bioactive luteinizing hormone surge in ovariectomized monkeys

Progestins facilitate estrogen induction of the preovulatory luteinizing hormone (LH) surge. A biologically weaker progestin, 20α-dihydroxyprogesterone, is reportedly increased at midcycle, but the importance of 20α-dihydroxyprogesterone in regulating LH release has not been systematically studied. We therefore evaluated the effect of 2 doses of 20α-dihydroxyprogesterone on the bioactive LH surge onset in ovariectomized monkeys. Chronically cannulated monkeys (n = 10) received estradiol (E₂) benzoate (50 μg/kg) with and without subsequent 20α-dihydroxyprogesterone injections (50 μg/kg, n = 3 and 100 μg/kg, n = 3). Blood was collected every 15 minutes over preselected intervals and the plasma assayed for bioactive LH and gonadal steroids. Low-dose 20α-dihydroxyprogesterone administration resulted in periovulatory peripheral 20α-dihydroxyprogesterone levels and did not advance the bioactive LH surge onset. In contrast, high-dose 20α-dihydroxyprogesterone resulted in supraphysiological 20α-dihydroxyprogesterone levels, slight increases in progesterone levels, and significant advancement of the surge over E₂ benzoate treatment alone. We conclude that periovulatory levels of 20α-dihydroxyprogesterone do not play a role in modulating the estrogen-induced bioactive LH surge.