GENES, PROGESTINS, AND FEMALE REPRODUCTIVE BEHAVIOR

孕酮(P)促进性接受行为的表达 在非灵长类雌性哺乳动物中存在，并被认为与 人类的周期性情绪变化(经前综合症)。其作用机制 P和它的初级代谢物5α-二氢黄体酮 (DHP)，影响神经组织和行为，然而，还没有 完全被描述过。因为受体结合被认为是关键 在产生类固醇介导的效应的第一步，目标是 拟议的研究将考察P和DHP与 大脑中的细胞孕激素受体(PR)。这将会实现的 通过建立一种可使用~3H-P和~3H-DHP的神经PR检测方法 作为配基，这是一种目前不可用的程序。化验结果会 然后用来比较两个品系的小鼠(CD-1， 对行为影响有不同的敏感性 P和DHP。由于CD-1女性对两种孕激素都有反应，而Sw 雌性对DHP不敏感，品系比较应提供 用于表征敏感性的可能分子基础的有力工具 对P和DHP不敏感)，以及提供有关 这些受体的诱导。因此，结果应该提供 对周期性的一个主要神经内分泌过程的洞察 女性的行为变化，也可能有助于产生新的假设 孕激素在经前综合征中的可能作用。

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.