Comparative Physiology of Pituitary Hormones: Regulation of Secretion

本研究的目的是获得关于调节异温脊椎动物垂体激素合成和分泌机制的基本信息，最初的重点将放在控制促甲状腺激素（TSH）和促性腺激素（FSH和LDH）分泌的下丘脑因子以及调节爬行动物和两栖动物垂体对这些因子敏感性的外周因子上。幼小的海龟将作为爬行动物系统的模型，牛蛙将作为两栖动物系统的模型，与其他目进行有限的比较。A.促甲状腺激素分泌：促甲状腺激素的调节将集中在下丘脑三肽，促甲状腺激素释放激素（TRH）的作用上，其在两栖动物和爬行动物中的作用尚不清楚。我们还将研究来自大脑和外周的潜在刺激剂和抑制剂的作用，特别是甲状腺激素，它们可能调节垂体对TRH的反应。急性和慢性热效应对垂体反应将检查在外源性控制的背景下。在所有的研究中，将尝试同时分析垂体生长激素和催乳素的反应，并在体外平行测量甲状腺TSH敏感性。B.促性腺激素分泌：对促性腺激素调节的研究将有两个重点：1)类固醇在调节垂体对促性腺激素释放激素的敏感性中的作用，将研究与对这种下丘脑肽的反应性二态性的发生和维持有关。2)将首次关注非甾体性腺分泌物（基于哺乳动物抑制素）在垂体FSH和LH分泌差异调节中的作用。这些研究为了解异温四足动物下丘脑-垂体调节的进化及其与外周内分泌靶点的整合提供了基础。

The goal of this proposal is to obtain basic information on the mechanisms by which the synthesis and secretion of pituitary hormones are regulated in ectothermal vertebrates The initial focus will be on hypothalamic factors that control thyrotropin (TSH) and gonadotropin (FSH and LDH secretion and on peripheral factors that modulate pituitary sensitivity to these factors in reptiles and amphibians. The young turtle will serve as a model reptilian system and the bullfrog will serve as an amphibian model, with limited comparisons with other orders. A. TSH Secretion: TSH regulation will focus on the role of the hypothalamic tripeptide, thyrotropin-releasing hormone (TRH), whose role in amphibians and rrptiles is poorly understood. We will also examine actions of potential stimulators and inhibitors from the brain and periphery, especially thyroid hormones, that may modulate pituitary responsiveness to TRH. Acute and chronic thermal effects on pituitary responsiveness will be examined in the context of exogeous control. Attempts will be made to analyze pituitary growth hormone and prolactin responses concomitantly in all studies, and in vitro thyroidal TSH sensitivity will be measured in parallel. B. Gonadotropin Secretion: Studies on the regulation of gonadotropin will have two foci:1) The role of steroids in modulating pituitary sensitivity to gonadotropin releasing hormone will be studied in relation to the ontogeny and maintenance of sexual dimorphism in responsiveness to this hyhpothalamic peptide. 2) Attention will be directed for the first time to the role of nonsteroidal gonadal secretions (based on mammalian inhibin) in differentially modulating pituitary FSH and LH secretion. These studies should provide a foundation for understanding the evolution of hypothalamo-pituitary regulation and its integration with peripheral endocrine targets in ectothermal tetrapods.