GENES, PROGESTINS, AND FEMALE REPRODUCTIVE BEHAVIOR

黄体酮 (P) 促进性接受行为的表达 在非灵长类雌性哺乳动物中，并且与以下疾病的病因学有关 人类的周期性情绪变化（经前综合症）。 机制 P 及其主要代谢物 5α-二氢孕酮 （DHP），影响神经组织和行为，然而，尚未被证实 完全描述。 因为受体结合被认为是一个关键 产生类固醇介导效应的第一步，目标 拟议的研究将检查 P 和 DHP 与 大脑中的细胞孕激素受体（PR）。 这将实现 通过开发一种可以使用 3H-P 和 3H-DHP 的神经 PR 检测方法 作为配体，目前尚无法实现这一过程。 该测定将 然后用于比较两种小鼠品系（CD-1、 Swiss-Websster）对行为影响有不同的敏感度 P 和 DHP。 由于 CD-1 雌性对两种孕激素都有反应，而 SW 雌性对 DHP 不敏感，菌株比较应提供 表征灵敏度可能的分子基础的强大工具 （或不敏感）P 和 DHP 以及提供有关 这些受体的诱导。 因此，结果应提供 深入了解参与周期性的主要神经内分泌过程 女性的行为变化也可能有助于产生新的假设 关于孕激素在经前综合症中的可能作用。

Progesterone (P) facilitates the expression of sexually receptive behaviors in non-primate female mammals and has been implicated in the etiology of cyclical mood changes in humans (premenstrual syndrome). The mechanisms through which P and its primary metabolite, 5Alpha-dihydroprogesterone (DHP), affect neural tissues and behavior, however, have not yet been completely described. Because receptor binding is recognized as a critical first step in the production of steroid-mediated effects, the goal of the proposed research will be to examine the interaction of P and DHP with cellular progestin receptors (PR) in the brain. This will be accomplished by developing an assay for neural PR in which 3H-P and 3H-DHP can be used as ligands, a procedure which is currently unavailable. The assay will then be used to compare P and DHP binding in two strains of mice (CD-1, Swiss-Websster) that are differentially sensitive to the behavioral effects of P and DHP. Since CD-1 females respond to both progestins while SW females are insensitive to DHP, the strain comparison should provide a powerful tool for characterizing a possible molecular basis for sensitivity (or insensitivity) to P and DHP as well as providing information about the induction of these receptors. The results should therefore provide insights into a major neuroendocrine process involved in cyclical behavioral changes in females and may also help generate new hypotheses concerning the possible role of progestins in premenstrual syndrome.