NEUROENDOCRINE REGULATION OF EPISODIC LH RELEASE

该研究计划的总体目标将是确定 中枢性发生的事件对基础的调节至关重要 生殖系统两个重要时期的搏动性促黄体生成素释放 生理学--发情周期和妊娠。 发情周期：我们已经证明了分泌物的每日变化 大鼠发情周期中雌二醇(E_2)和/或孕酮(P)的变化 在调节基础搏动的差异方面至关重要 黄体生成素的释放发生在每个周期阶段。这些类固醇的作用 建议在中枢神经系统水平发挥作用。关于 间情期1-间情期2(D2)和D2-发情周期的间隔期， 具体目标包括确定神经递质的调节作用 生理水平的E_2和/或P对黄体生成素的负反馈作用 每24小时间隔内的脉冲幅度和/或频率以及LHRH的变化 E_2和/或P的抑制作用引起的分泌 各间期脉冲式促黄体生成素释放的变化。 怀孕：我们还证明了促黄体生成素的释放是脉动的 在大鼠怀孕期间，血液中黄体生成素水平的增加 发生在分娩前(第22天)是由于黄体生成素脉搏增加 频率此外，正在进行的工作表明，内源性阿片类药物 多肽(EOPs)对搏动性黄体生成素的紧张性抑制作用 在整个怀孕期间分泌，但促黄体生成素的脉冲频率不是 在妊娠的每个阶段被EOPs抑制。关于 妊娠结束时促黄体生成素脉冲性释放的复苏，特定目标 现在包括确定血浆P水平在第22天的下降 是此时黄体生成素脉冲频率增加的基础，如果是这样的话， P的抑制作用是否至少部分是通过 EOPS，以及内侧视前区或弓状正中隆起 区域是参与黄体生成素的P依赖、EOP抑制的神经基因座 脉冲频率，以及确定血浆P 妊娠末期血清LHRH水平和LHRH分泌。 利用连续采血、推拉灌流采集血液标本 脑灌流液，高效液相色谱仪 测定神经递质和激素的电化学检测 放射免疫分析，这个项目将继续我们对神经和 生理状态下调节脉动性促黄体生成素释放的内分泌因素 条件。收集的数据将为我们更好地理解 生殖神经内分泌生理学，很可能是重要的 在临床上对生殖疾病的认识、诊断或治疗 精神错乱。

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.