Further Studies on the Effect of Exogenous Progesterone and Related Compounds on the Preovulatory Progesterone Secretion in the Rat

Abstract
Further studies were made in 4-day cyclic rats on the action of exogenous progesterone in advancing the release of LH from the pituitary, evidenced by the earlier increase in ovarian progesterone secretion than the spontaneous preovulatory increase in secretion of this steroid. It was found that 1) exogenous progesterone injected subcutaneously during the period from 03.00 to 13.00 hr of proestrus increased the rate of ovarian progesterone secretion at 16.00 hr on that day, one hr earlier than the time of the spontaneous increase corresponding to the onset of LH release, maximal increase being induced by progesterone given at 11.00 hr, injections at 01.00 or 15.00 hr failed to increase the secretion; 2) a linear dose-response relationship between the secretory rate of progesterone and the log-dose of progesterone injected at 11.00 hr was obtained in the dosage range of 0.05 to 5 mg per rat; 3) advanced increase in progesterone secretion caused by an adequate amount of progesterone was seen around 14.00 hr at the earliest, regardless of the time of progesterone injection, i.e. the advancement of LH release by exogenous progesterone never exceeded 3 hr; 4) desoxycorticosterone (DOC), norethisterone and medroxyprogesterone acetate (MAP) exerted a similar effect but corticosterone and medroxyprogesterone did not; 5) the progesterone secretory rate at 16.00 or 19.00 hr in rats sufficiently primed with progesterone was almost double the maximal value obtained at the peak of LH release in intact rats, and such a “supersecretion” of progesterone was not obtained by an LH preparation, even when given in excess; 6) 20α-hydroxypregn-4-en-3-one (20α-OH-P) secretion was not always parallel with progesterone secretion under the various conditions described above; and 7) treatment with 5 mg of progesterone, medroxyprogesterone, corticosterone or DOC increased the ovarian secretory rate of 20α-OH-P but either smaller doses of progesterone, or the treatment before 05.00 hr on the day of proestrus, appeared to depress the secretion of this steroid.From these results, it is suggested that exogenous progesterone not only acts on the neural process regulating the ovulating hormone release from the pituitary but also affects the ovary to increase its responsiveness to pituitary gonadotropins, and thus advances the release of ovulating hormone and causes the supersecretion of progesterone at the preovulatory state. It is further suggested that exogenous progesterone and synthetic progestins directly or indirectly affect the ovarian production of 20α-OH-P.