STEROID HORMONE REGULATION OF TSH SUBMIT BIOSYNTHESIS

促甲状腺激素的主要调节因素是甲状腺激素(负反馈)。这个 糖皮质激素和性类固醇激素也是重要的调节因子 太好了。TSH是一种二聚体，由它与之共有的阿尔法亚单位组成 其他几种荷尔蒙，以及一种特定的β-亚基。这些亚单位是 从单独的mRNA合成的，这表明了基本的问题 关于它们的协调或非协调调节。申请人的 先前的研究证明TSH-Beta和Alpha的调节不一致 甲状腺激素。 糖皮质激素对TSH的抑制作用可能通过类似于 甲状腺激素的含量。在用糖皮质激素进行体内治疗后， 携带促甲状腺肿瘤的小鼠，一种只含有促甲状腺激素的组织 从甲状腺功能减退的脑垂体中提取，将被杀死并进行血浆分析， 垂体、肿瘤TSH和亚单位浓度通过特定的RIA测定。核糖核酸 将被分离出来用于测定α基因的稳定水平 和TSH-β通过与特异的cDNAs探针杂交。转录 将测量mRNAs的速率、mRNA稳定性和翻译产物， 并探讨了非协调亚单位调控的可能性。 睾酮抑制黄体生成素及其共同的α亚基的合成 与TSH共享。阿尔法基因只有一个拷贝。在老鼠身上， 睾酮增加血浆促甲状腺激素浓度；如果睾酮也 增加促甲状腺激素α的合成，这表明 睾酮α是细胞特异性的(促甲状腺激素与促性腺激素)。 甲状腺肿瘤中蛋白质和信使核糖核酸浓度的测定 去势垂体(一种富含促性腺激素的组织)将解决 与单个细胞特异性调控有关的基本问题 吉恩。使用雌激素的协议将解决类似的问题。 罗斯博士毕业于哈佛医学院，完成了他的内科 医学和内分泌培训在弥撒。他去过的综合医院 自1981年7月起在甲状腺单位接受研究培训。他的基础研究 促甲状腺激素亚单位生物合成的不协调调节 到目前为止的出版物(1个待定)，他是3个月的第一作者。 此外，他还完成了3个临床项目。他计划进行一项学术研究 以基础研究为重点的事业。弥漫性甲状腺单位。一般信息 医院为年轻的调查员提供了一个出色的环境。 实验室内有基础广泛的专业知识，以及 杰出的实验室使用最新的分子技术 生物学和分子遗传学可在 医院。

The major regulator of TSH is thyroid hormone (negative feedback). The glucocorticoid and sex steroid hormones are also important modulators of TSH. TSH is a dimer composed of an Alpha-subunit which it shares with several other hormones, and a specific Beta-subunit. These subunits are synthesized from separate mRNAs, which suggest fundamental questions concerning their coordinate or non-coordinate regulation. The applicant's prior research documented discordant regulation of TSH-Beta and Alpha by thyroxine. Glucocorticoid inhibition of TSH may occur via a mechanism similar to that of the thyroid hormones. Following in vivo treatment with glucocorticoids, mice bearing thyrotropic tumors, a tissue containing only thyrotropes derived from hypothyroid pituitary, will be killed and analyzed for plasma, pituitary, and tumor TSH and subunit concentrations by specific RIAs. RNA will be isolated for determination of steady-state levels of mRNA for Alpha and TSH-Beta by hybridization to specific cDNA probes. Transcription rates, mRNA stability, and translation products of mRNAs will be measured, and the possibility of noncoordinate subunit regulation will be explored. Testosterone inhibits synthesis of LH and the common Alpha-subunit which LH shares with TSH. There is only one copy of the Alpha gene. In the mouse, testosterone increases plasma TSH concentration; if testosterone also increases thyrotrope Alpha synthesis, this suggests that the effects of testosterone Alpha is cell specific (thyrotrope vs gonadotrope). Measurement of protein and mRNA concentrations in thyrotropic tumors and castrate pituitaries (a gonadotrope enriched tissue) will address fundamental questions concerning cell-specific regulation of a single gene. Protocols using estrogen will address similar questions. Dr. Ross, a graduate of Harvard Medical School, completed his internal medicine and endocrine training at Mass. General Hospital where he has been a research trainee in the Thyroid Unit since July 1981. His basic research on discordant regulation of TSH subunit biosynthesis has yielded 5 publications to date (1 pending) of which he is first author on 3. Additionally, he has completed 3 clinical projects. He plans an academic career with emphasis on basic research. The Thyroid Unit at Mass. General Hospital provides an outstanding environment for a young investigator. There is broad-based expertise within the laboratory, as well as outstanding laboratories using the most up-to-date techniques in molecular biology and molecular genetics available for consultation within the hospital.