NEUROENDOCRINE REGULATION OF EPISODIC LH RELEASE

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The overall objective of this research program will be to determine the centrally-occurring events that are crucial to the regulation of basal pulsatile LH release during two important periods in reproductive physiology--the estrous cycle and pregnancy. I. ESTROUS CYCLE: We have demonstrated that the daily changes in secretory patterns of estradiol (E2) and/or progesterone (P) in the rat estrous cycle are critically important in regulating the differences in basal pulsatile LH release that occur at each cycle stage. The actions of these steroids were suggested to be exerted at the level of the CNS. With respect to the diestrous 1-diestrous 2 (D2) and D2-proestrous intervals of the cycle, specific aims include determining neurotransmitter mediation of the negative feedback actions of physiological levels of E2 and/or P on LH pulse amplitude and/or frequency in each 24 h interval, and changes in LHRH secretion occurring in response to the suppressive actions of E2 and/or P on pulsatile LH release in each interval. II. PREGNANCY: We have also demonstrated that LH release is pulsatile during pregnancy in the rat and that the increase in blood LH levels occurring prior to parturition (day 22) is due to an increase in LH pulse frequency. In addition, work in progress has shown tht endogenous opioid peptides (EOPs) exert a tonic suppressive influence on pulsatile LH secretion throughout pregnancy, but that LH pulse frequency is not suppressed by EOPs at each stage of gestation. With respect to the resurgence of pulsatile LH release at the end of pregnancy, specific aims now include determining whether the decline in plasma P levels on day 22 underlies the increase in LH pulse frequency at this time, and if so, whether the suppressive effect of P is exerted at least in part via the EOPs, and whether the medial preoptic area or arcuate-median eminence regions are neural loci involved in P-dependent, EOP suppression of LH pulse frequency, as well as determining the relationship between plasma P levels and LHRH secretion at the end of pregnancy. Utilizing continuous blood sampling, push-pull perfusion for collection of brain perfusates, high performance liquid chromatography with electrochemical detection for measurement of neurotransmitters, and hormone radioimmunoassays, this program will continue our studies of neural and endocrine factors regulating pulsatile LH release under physiological conditions. The data gathered will provide a sounder understanding of reproductive neuroendocrine physiology, and may well be important clinically in the understanding, diagnosis or treatment of reproductive disorders.