AGE RELATED CHANGES IN PITUITARY LACTOTROPHS

这项提议的具体目的是描述与年龄有关的特征 垂体前叶催乳素反应的改变。的主要关注点 这项工作将是关于细胞信号转导机制的研究 催乳素，特别是磷脂酰肌醇-4，5- 二磷酸(PIP2)。这会导致肌醇磷酸盐的积累。 (IPS)，特别是1，4，5-三磷酸肌醇(IP3)，它是一种 细胞内的第二信使。催乳素分泌和细胞含量， 肌醇磷酸盐积累和磷脂代谢将 在来自脑下垂体前叶的原代培养中确定 三个不同年龄的捐赠者群体，即年轻(3-4个月)、成熟(7-8个月) 月)和老年(22-24月龄)的雄性和雌性SD大鼠。 培养物将用促分泌剂(TRH、血管紧张素II或 神经降压素)，已被证明通过PIP2增加催乳素的释放 水解液。这些促分泌剂的刺激活性以及 多巴胺抑制这些反应的能力将被确定。在……里面 为了区分受体结合的可能差异 这些促分泌剂的特性，受体将被绕过 佛波醇酯的管理。此外，还涉及到 雌激素对脑下垂体反应性的影响将被确定。这将会是 以两种不同的方式完成。首先，一些雌性老鼠将被 在3-4个月时切除卵巢，并将其作为单独的一组垂体 每个老年群体(即成熟群体和老年群体)的捐助者。第二， 雌激素对脑垂体的直接影响将通过添加它来评估。 向文化致敬。将量化所有捐赠者群体中的乳酸菌数量 所有细胞都将在不含类固醇的培养液中孵化。 衰老会在许多生理功能上产生许多变化。 内分泌系统发生了重大变化，包括 垂体前叶分泌功能，最值得注意的是， 催乳素分泌。衰老也明显地与 垂体腺瘤(涉及催乳素种群)。因此， 垂体前叶催乳素反应性的改变可能 可作为垂体腺瘤的早期标志物。重要的是要了解 陈化过程的特征(S)和机制(S) 正常衰老与老年发病机制的关系-- 可以确定相关疾病，特别是考虑到 这一地区的人口结构日益向老年人口转移 国家。

The specific aim of this proposal is to characterize age-related alterations in anterior pituitary lactotroph responses. A major focus of this work will be on the cell signal transduction mechanism of the lactotroph, specifically the hydrolysis of phosphatidyl-inositol-4,5- bisphosphate (PIP2). This produces an accumulation in inositol phosphates (IPs), notably inositol 1,4,5-triphosphate (IP3) which serves as an intracellular second messenger. Prolactin secretion and cell content, inositol phosphate accumulation and phospholipid metabolism will be determined in primary cultures derived from anterior pituitary glands from three different aged donor groups, i.e. young (3-4 months), mature (7-8 months) and old (22-24 months) male and female Sprague-Dawley rats. Cultures will be treated with secretagogues (TRH, Angiotensin II or neurotensin) which have been shown to increase prolactin release via PIP2 hydrolysis. The stimulatory activity of these secretagogues, as well as the ability of dopamine to inhibit these responses will be determined. In order to distinguish between possible differences in receptor binding characteristics of these secretagogues, the receptors will be by passed by administration of phorbol esters. The addition, the involvement of estrogen on pituitary responsiveness will be determined. This well be accomplished in two different ways. First, a number of female rats will be ovariectomized at 3-4 months and included as a separate group of pituitary donors for each of the older groups (i.e. mature and old). Second, the direct effects of estrogen on the pituitary will be assessed by adding it to the cultures. Lactotroph number will be quantified in all donor groups and all cells will be incubated in steroid free media. Aging produces a number of alterations in many physiologic functions. Significant changes occur in the endocrine system, including alterations in anterior pituitary secretory function, most notable, an increase in prolactin secretion. Aging is also clearly associated with an increase in pituitary adenomas (which involves the lactotroph population). Thus, alterations in the responsiveness of the anterior pituitary lactotroph may be an early marker of pituitary adenomas. It is important to understand the characteristic(s) and mechanism(s) associated with the aging process so that the relationship between normal aging and the pathogenesis of age- related diseases can be determined, especially taking into consideration the growing shift in demographics toward the elderly population in this country.