The overall objective is to learn as much as possible about the control and dynamics of ovarian hormone production during pregnancy, particularly during the period of transition from pituitary to placental regulation of ovarian function. Other than progesterone (P) and estradiol (E2), the major ovarian steroid in which we are interested is testosterone (T), as a consequence of our earlier demonstration of a midpregnancy androgen surge which varies in magnitude in strains of mice that differ in reproductive performance. The immediate objectives are grouped into three areas: androgen and pregnancy, genetic variation in endocrine function, and estrogen activity in the female mouse. In the area of androgen during pregnancy, we will determine the source, regulation and function of the midpregnancy testosterone surge. The site(s) of ovarian T production (luteal and/or nonluteal) will be ascertained using in vitro and in vivo techniques; the relative roles of pituitary and placental hormones in the control of T secretion will be assessed in pregnant and psuedopregnant mice subjected to hypophysectomy and/or hysterectomy or bearing decidual as compared to trophoblastic tissues; the function of the midpregnancy T surge will be investigated by inhibiting T biosynthesis, by using androgen antogonists, and by performing endocrine ablation and steroid replacement experiments. Studies on genetic variation in endocrine function are directed toward elucidating the basis of strain differences in steroid secretion and toward exposing the rate-limiting factors in androgen production. Using mice selected for various traits, we will examine ovarian responsiveness to gonadotropic stimulation and ovarian enzyme activities in strains with naturally-occurring high, intermediate and low T levels. We will also use embryo transfer to partition maternal from placental-fetal effects on steroid production during pregnancy. In the area of estrogen activity, we will isolate and define as yet unidentified components of plasma and urine which have demonstrated estrogen-like immuno- and biopotency. The physiological significance of these unknown compounds will be determined as well as their relationship to estradiol.
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