The rat ovary secretes, in addition to progesterone, a series of other related steroids. Among these are prominent 20a-hydroxypregn-4-en-3one (20a-progesterone7 20a-P) (1-6), and its Sa-reduced metabolite 5a-pregnane-3a, 20a-diol(5a-diol) (6-8) (see Fig. 1). The anterior pituitary, the hypothalamus and other nervous structures of the rat (9-12) are able to convert progesterone into Sa-pregnane-3,20-dione (Sa-DHP) and into Sa-pregnane-3a-ol-20-one (3a-OL) (see Fig. I). More recently, it has been demonstrated that the neuroendocrine tissues are also able to convert progesterone into 20a-P, and subsequently into Sa-pregnan-2Oalpha-ol-3-one (20a-DHP), and Sa-diol (13-15). 2Oa-P has been shown to be an even better substrate for the Sa-reductase of the rat anterior pituitary (16).Progesterone is known to induce ovulation and to facilitate LH release in the female rat (17), and is believed to play a physiological role in the neuroendocrine processes leading to the preovulatory gonadotropic surge in this species (18)(19)(20)(21)(22). The participation of 20alpha-P in these processess is suggested by the fact that the secretion of this steroid from the ovary increases at proestrus, before the initiation of the LH preovulatory surge (1-5, 23). Moreover, it has been shown that 20alpha-P is able to release LH and FSH in ovariectomized estrogen-primed rats (1 8, 19). Finally, Hilliard and coworkers (24) have suggested that 20a-P may amplify the amounts of LH released after mating in rabbits. However, divergent data have also appeared. For instance, Fink and Henderson (20) were unable to obtain gonadotropin release in estrogenprimed female rats after administering 20a-P, and Goodman and Neil1 (25) could not du-~ ~ -~~ ~~ This work was supported by a grant from the Italian National Council of Research (CNR) through the project "Biology of Reproduction" and by a grant from the Ford Foundation, New York, NY. plicate the results of Hilliard et al. (24) in does.In recent studies, it has been shown that the physiological Sa-reduced metabolites of progesterone Sa-DHP and 3a-OL, are able to provoke a large release of LH and FSH when given to castrated-estrogen-primed female rats (19-2 1,26). The present investigation has been performed: (a) to gain additional information on the effects of 2Oa-P on the control of gonadotropin release; and (b) to determine whether the Sa-reduced metabolite of 20a-P, Salpha-DIOL might exert any effect on gonadotropin secretion. To the authors' knowledge, the activity of this steroid on gonadotropin release has never been investigated.Materials and methods. Animals. All experiments have been performed in adult female rats of the Sprague-Dawley strain. Animals were caged in rooms with controlled temperature and humidity (lights on from 6.30 to 20.30); they were fed with a standard pellet diet and water was allowed ad libitum.In order to analyse whether the two steroids might exert a stimulatory effect on gonadotropin release, an approach similar to that of Swerdloff et al. (18) was adopted. These authors h...