CNS FUNCTION OF GHRH RELATED PEPTIDE

生长激素促分泌素（GHS）的发现扩大了我们对生长激素（GH）分泌调节的理解。 虽然这些GHS的受体已被确定，但内源性配体仍然未知。 我们假设，第二个肽来源于羧基末端的GHRH基因是一个内源性GHS配体。 这种新发现的肽，GHRH相关肽（GHRH-RP）在大脑和睾丸中发现。 睾丸GHRH-RP的生物学作用已被确定，但GHRH-RP在大脑中的作用尚不清楚。 该项目有望扩大我们对生长激素轴复杂调控的认识。虽然它被设计为一个基础研究项目，但它对临床研究有重要意义。所产生的数据可以推进对生长异常儿童的诊断评估和干预策略。 我们的假设将通过以下方式进行检验：1。a.我们将确定是否GHRH-RP行为，以调节生长激素的生产和释放，在体外使用原代垂体前叶细胞培养。 还将测量GHRH-RP处理对GH表达水平、GHS受体、ACTH、TSH、催乳素、LH、FSH水平的影响。B.我们将研究GHRH-RP激活的第二信使系统，包括PKC和PKA通路。 2.我们将描述GHRH-RP的体内CNS效应。 a.将GHRH-RP抗血清直接脑室内给药至大鼠脑中，并确定对生长、行为、生育力和喂养模式变化的影响。 B.将评估GHRH-RP对下丘脑GHS受体和生长抑素表达的体内作用。还将评价其他因素，包括GH、催乳素、ACTH、TSH、催乳素、LH和FSH水平。

The discovery of Growth Hormone Secretagogues (GHS) has expanded our understanding of the regulation of Growth Hormone (GH) secretion. Although the receptor for these GHS has been identified, the endogenous ligand(s) remains unknown. We hypothesize that a second peptide derived from the carboxyl- terminal end of the GHRH gene is an endogenous GHS ligand. This newly discovered peptide, GHRH Related Peptide (GHRH-RP) is found in the brain and the testes. A biologic action for testicular GHRH-RP has been identified, but GHRH-RP's action in the brain is not yet understood. This project is expected to expand our knowledge of the complex regulation of the growth hormone axis. Although it is designed as a basic research project, it has important implications for clinical research. The diagnostic evaluation and intervention strategies available for children with growth abnormalities could be advanced by the data generated. Our hypothesis will be tested in the following manner: 1. a. We will determine whether GHRH-RP acts to regulate GH production and release in vitro using primary anterior pituitary cell cultures. The effects of GHRH-RP treatment on the level of expression of GH, the GHS receptor, ACTH, TSH, prolactin, LH, FSH levels will also be measured. b. We will examine the second messenger systems activated by GHRH-RP including the PKC and PKA pathways. 2. We will characterize the in vivo CNS effects of GHRH-RP. a. Direct intracerebroventricular administration of GHRH-RP antisera into the rat brain will be performed and the effects on changes in growth, behavior, fertility and feeding patterns will be determined. b. The in vivo effect of GHRH-RP on hypothalamic expression of the GHS receptor and somatostatin will be assessed. Other factors including GH, prolactin, ACTH, TSH, prolactin, LH and FSH levels will also be evaluated.