ACTIVIN REGULATION OF SMAD7 IN THE PITUITARY

激活素在调节垂体-性腺轴中起关键作用。本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，为这种理解奠定基础。我们实验室的初步数据显示Smad7在垂体前叶表达。虽然很明显Smad7是激活素信号的拮抗剂，但其在垂体中的作用仍未得到充分研究。我们假设Smad7是垂体内一个重要的调节因子，抑制激活素调节的垂体细胞功能。在Specific Aim I中，研究将在体外研究大鼠垂体前叶细胞中Smad7表达的产生和调控。在Specific Aim II中，研究旨在表征小鼠促性腺激素细胞系中Smad7基因的结构及其通过激活素的调节。最后，在Specific Aim III下，我们建议研究Smad7在基础和激活素调节的促性腺细胞功能中的作用。本研究计划中概述的研究非常重要，因为确定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垂体功能障碍治疗工具的重要一步。

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.