The following research objectives will be carried out. Using a potent GnRH antagonist ((Ac-dehydro-Pro1, pC1-d-Phe2, D-Trp3,6)-N-Alpha-MeLeu-GnRH) we will examine the relative dependency of FSH and LH secretion rates on GnRH. We will also determine if follicular fluid can be shown to suppress LH secretion in vivo as it does in vitro under GnRH stimulation. Gonadal feedback control of FSH and LH will be examined in several experiments. The role of estradiol feedback in the delay of LH rise following ovariectomy will be tested. The necessity of the dorsal anterior hypothalamic area (DAHA) for the singular rise of FSH during the secondary surge or following ovariectomy will be investigated. We will also determine if the relative inadequacy of estradiol in triggering a primary FSH surge is due to its inadequacy in first suppressing serum FSH in ovarectomized recipients. Ovarian translantation models will also be used to study FSH and LH regulation. Mechanisms of stress interference with FSH and LH secretion will be investigated by examining the intervention of the adrenal-pituitary axis in the acute LH and FSH response to loss of testis feedback. The role of prolactin and progesterone in the blockade of ovulation by pentobarbital administration will be studied. The effect of neonatal hormone treatment on several sexually dimorphic aspects of tonic regulation of LH and FSH will be examined. In terms of health-related implications, the world faces the problem of enhancing fertility in some cases and preventing it under other circumstances. We feel that a series of approaches, such as we represent, is called for in attacking the multiple problems faced by society with respect to population.
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