NEURAL REGULATION OF FSH--GNRH RELEASE AND FEEDBACK MECHANISMS

FSH的释放可能受脉冲放电控制 一种或多种释放因子进入下丘脑- 垂体门脉系统，也通过内分泌反馈 性腺起源的机制。 目前尚不清楚是否相同 调节LH分泌的下丘脑释放因子- 十肽GnRH -也控制 FSH，或者如果一种独特的FSH释放因子发挥主导作用， 下丘脑对FSH释放的控制。 同样， GnRH系统参与选择性内分泌反馈 促性腺激素释放的调节是未知的。 拟议 实验，新的体内技术，如下丘脑推- 牵拉灌注、垂体微透析和GnRH放射性配体 受体测定将用于辨别这些基本的下丘脑- 垂体-性腺关系 促性腺激素释放激素在 将首先阐明雄性大鼠中FSH脉冲的刺激 通过同时测量下丘脑中GnRH的释放 外周血中的推挽式灌注液（或垂体透析液）和FSH 等离子体 GnRH脉冲频率在选择性 FSH分泌的调节将使用脉冲式 垂体切除大鼠不同频率的GnRH输注 进行脑垂体移植 在第二项研究中， 性腺类固醇对GnRH和FSH分泌的反馈将是 进行。 同时测量GnRH和 将在去势大鼠中进行促性腺激素释放 在对照或睾酮治疗后， 去势和激素诱导的FSH分泌变化是 与GnRH释放的改变有关。 生理 任何观察到的去势或类固醇诱导的 将在大鼠中评估内源性GnRH释放的变化 进行垂体移植;内源性GnRH模式将是 模拟外源性GnRH输注，FSH分泌 将监测对去势和类固醇治疗的反应。 在第三项研究中， 促性腺激素卵泡抑素对FSH分泌的作用 将确定; GnRH和FSH释放将在 完整和去势雄性大鼠之前和之后的全身或 下丘脑内施用猪卵泡液。 促性腺激素对GnRH敏感性的潜在反馈调节 和/或促性腺激素释放激素受体水平的卵泡抑素也将被 考察 这些研究将提供大量新的 关于FSH基本生理控制的信息 通过几种重要的神经内分泌机制分泌。

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.