ACTIVIN REGULATION OF SMAD7 IN THE PITUITARY

激活素在垂体-性腺轴的调节中起关键作用。 拟议研究的长期目标是更好地了解激活素在垂体细胞生理调节中的作用。 短期目标是通过回答有关激活素信号转导机制的一些具体问题来建立这种理解的基础。 我们实验室的初步数据表明Smad 7在垂体前叶表达。 虽然很明显Smad 7是激活素信号传导的拮抗剂，但其在垂体中的作用在很大程度上尚未探索。 我们推测Smad 7是垂体内的一个重要调节因子，抑制激活素调节的垂体细胞功能。 在特定目标I中，研究将在体外检查大鼠垂体前叶细胞中Smad 7表达的产生和调节。 在特定目标II中，研究旨在表征小鼠Smad 7基因的结构及其在促性腺细胞系中通过激活素的调节。 最后，根据具体目标III，我们建议研究Smad 7对基础和激活素调节的促性腺细胞功能的作用。 本研究提案中概述的研究非常重要，因为定义激活素信号通路是更好地理解激活素的内分泌作用，各种内分泌疾病的发病机制以及开发治疗垂体功能障碍的工具的pivitol步骤。

Activin plays a critical role in the regulation of the pituitary-gonadal axis. The long-term objectives of the proposed research are to better understand the role of activin in the regulation of pituitary cell physiology. The short-term goals are to establish the basis for this understanding by answering some specific questions concerning the mechanisms underlying activin signal transduction. Preliminary data from our laboratory demonstrates Smad7 expression in the anterior pituitary. While it is clear that Smad7 is an antagonist of activin signaling, its role in the pituitary remains largely unexplored. We hypothesize that Smad7 is an important modulatory factor within the pituitary, inhibiting activin-regulated pituitary cell function. In Specific Aim I, studies will examine the production and regulation of Smad7 expression in rat anterior pituitary cells, in vitro. In Specific Aim II, studies aim to characterize the structure of the mouse Smad7 gene and its regulation by activin in a gonadotrope cell line. Lastly, under Specific Aim III, we propose to examine the role of Smad7 on basal and activin-regulated gonadotrope cell function. The studies outlined in the present research proposal are important as defining the activin signaling pathway is a pivitol step toward better understanding the endocrine role of activin, the pathogenesis of various endocrine disorders, and the development of tools toward the treatment of pituitary dysfunction.