The long-term goal of the proposed research is to elucidate the neuro- endocrine mechanisms whereby progesterone prevents short luteal phase cycles in ewes. It has been proposed that progesterone may prevent short luteal phases by promoting folliculogenesis, by stimulating luteal function, by preventing luteolysis, or a combination of these actions. Specifically, the proposed studies will examine whether progesterone modulates some of the parameters which promote folliculogenesis, namely gonadotropin secretion, or ovarian response to gonadotropins, or both. First, we will examine whether progesterone acts solely at the ovaries. Subsequent experiments will investigate whether progesterone ensures full-length luteal phases by modulating FSH or pulsatile LH secretion. Finally, the mechanism of action of progesterone in promoting folliculogenesis within the ovary will be investigated by measuring its effect on follicular steroid production and thecal and granulosa cell binding of 125I-hCG. Techniques include: radioimmunoassays for LH, FSH, estradiol, testosterone, and progesterone; sustained delivery of hormones via osmotic minipumps or Silastic implants; blood collection; cannulation of ovarian artery; active immunization against GnRH; ovariectomy; reversible termination of cycles with GnRH agonist; in vitro incubation of granulosa cells, ad measurement of ovarian thecal and granulosa cell LH receptors. The results of these studies should: (1) provide us with new insight into the neuroendocrine mechanisms controlling estrous cycles and their initiation and termination; (2) increase our knowledge of the mechanisms controlling recovery of cyclicity following treatment with GnRH agonist; (3) increase our understanding of the neuroendocrine control of short luteal phases and the prevention of short luteal phase infertility; and (4) provide us with new information regarding the role of progesterone in promoting folliculogenesis. Finally, these findings should be applicable to the clinical situations analogous to transitions between states of acyclicity and cyclicity, such as puberty, menopause, or those occurring following treatment of precocious puberty or endometriosis with GnRH agonists, or following use of GnRH agonists as contraceptives.
