NEUROENDOCRINE REGULATION OF EPISODIC LH RELEASE

这项研究计划的总体目标是确定 这些事件对调节基础代谢至关重要， 在生殖的两个重要时期的脉冲式LH释放 生理学--发情周期和怀孕。 I.动情周期：我们已经证明，分泌的每日变化， 大鼠动情周期中雌二醇（E2）和/或孕酮（P）的模式 在调节基础搏动的差异方面至关重要， LH释放发生在每个周期阶段。 这些类固醇的作用 建议在CNS水平发挥作用。 相对于 周期的动情间期1-动情间期2（D2）和D2-动情前期间期， 具体的目的包括确定神经递质介导的 生理水平的E2和/或P对LH的负反馈作用 每24小时间隔的脉冲幅度和/或频率，以及LHRH的变化 由于E2和/或P的抑制作用而产生的分泌 在每一个时间间隔的脉冲式LH释放。 二.妊娠：我们还证明LH的释放是脉动的， 在大鼠怀孕期间，血液LH水平的增加 在分娩前（第22天）发生，是由于LH脉冲增加 频率. 此外，正在进行的工作表明， 肽（EOP）对脉动LH产生紧张性抑制作用 分泌，但LH脉冲频率不是 在妊娠的每个阶段都受到了EOP的抑制。 相对于 妊娠结束时脉冲式LH释放的复苏，具体目标 现在包括确定第22天血浆P水平的下降是否 是此时LH脉冲频率增加的基础，如果是这样， P的抑制作用是否至少部分地通过 EOP，以及是否内侧视前区或眼内正中隆起 区域是参与P依赖性、EOP抑制LH的神经位点 脉冲频率，以及确定等离子体P 水平和LHRH分泌在怀孕结束。 采用连续采血、推拉灌注法采集 脑灌流液，高效液相色谱法 用于测量神经递质和激素的电化学检测 放射免疫测定，这个计划将继续我们的研究神经和 生理条件下调节LH脉冲释放的内分泌因子 条件 收集的数据将使人们更好地了解 生殖神经内分泌生理学， 临床上对生殖系统疾病的理解、诊断或治疗 紊乱

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.