NEURAL REGULATION OF FSH--GNRH RELEASE AND FEEDBACK MECHANISMS

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The release of FSH is likely controlled by the pulsatile discharge of one or more releasing factors into the hypothalamic- hypophysial portal vessel systems, and also by endocrine feedback mechanisms of gonadal origin. It is not known if the same hypothalamic releasing factor that regulates the secretion of LH - the decapeptide GnRH - also controls the pulsatile secretion of FSH, or if a distinct FSH-releasing factor exerts predominant hypothalamic control over FSH release. Likewise, the involvement of GnRH systems in the selective endocrine feedback regulation of gonadotropin release is unknown. In the proposed experiments, new in vivo techniques such as hypothalamic push- pull perfusion, pituitary microdialysis, and GnRH radioligand receptor assays will be used to discern these basic hypothalamic- hypophysial-gonadal relationships. The role of GnRH release in the stimulation of FSH pulses in male rats will first be clarified by simultaneous measurement of GnRH release in hypothalamic push-pull perfusates (or pituitary dialysates) and FSH In peripheral plasma. The importance of GnRH pulse frequency in the selective regulation of FSH secretion will be determined using pulsatile GnRH infusions of varying frequency in hypophysectomized rats bearing pituitary transplants. In a second study, an analysis of gonadal steroid feedback on GnRH and FSH secretion will be undertaken. Simultaneous measurements of GnRH and gonadotropin release will be carried out in castrated rats following control or testosterone treatment to determine if post- castration and steroid-induced changes in FSH secretion are associated with alterations in GnRH release. The physiological significance of any observed castration- or steroid-induced changes in endogenous GnRH release will be assessed in rats bearing pituitary transplants; endogenous GnRH patterns will be mimicked with exogenous GnRH Infusions, and FSH secretory responses to castration and steroid treatment will be monitored. In a third study the locus and mechanism of the negative feedback actions of the gonadal peptide folliculostatin on FSH secretion will be determined; GnRH and FSH release will be measured in intact and castrated male rats before and after the systemic or intrahypothalamic administration of porcine follicular fluid. Potential feedback regulation of gonadotropin sensitivity to GnRH and/or GnRH receptor levels by folliculostatin will also be examined. These studies will provide a substantial amount of new information regarding the basic physiological control of FSH secretion by several important neuroendocrine mechanisms.