HORMONES AND AGING--PITUITARY-HYPOTHALAMIC FUNCTION IN EXPERIMENTAL ANIMALS

激素与衰老--实验动物的垂体-下丘脑功能

• 批准号: 3808842
• 负责人: S MITCHELL HARMAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3808842
• 关键词: Macaca mulatta; Saimiri; adrenocorticotropic hormone; aging; animal age group; animal old age; diet; dopamine receptor; follicle stimulating hormone; gonadotropins; histochemistry /cytochemistry; hormone receptor; hormone regulation /control mechanism; hypothalamic pituitary axis; hypothalamus; immunocytochemistry; laboratory rat; luteinizing hormone; mature animal; messenger RNA; nutrition related tag; phorbols; pituitary gland; pituitary gonadal axis; prolactin; testis; thyroid gland; thyrotropin; tissue /cell culture

Continuing studies of pituitary tissues in the automated perifusion system confirm the observations of an age-related decrease in GnRH-stimulated LH secretion, previously shown in monolayer cultures. The failure to reverse the in vitro LH hyposecretion by repetitive perfusion pulses of GnRH parallels our prior observations after repetitive in vivo administration of GnRH and further suggests that aging is associated with an intrinsic pituitary gonadotropic secretary defect. Recent studies in primary monolayer cultures of heterogeneous pituitary cell suspensions reveal age-related decreases in secretion of LH after administration of the phorbol ester, PMA, a protein-kinase C activator as well as after nifedipine, a voltage gated calcium channel blocker. These observations suggest that both long and short term stimulation of LH release may proceed through separate mechanisms which are differentially affected by aging. Newer techniques for examining the cellular, biochemical, and molecular events responsible for age-related alterations in LH and PRL secretion have been introduced into our laboratory. These include; centrifugal elutriation, reverse hemolytic plaque assay, immunocytochemistry and immunofluorescence, RIA of G-protein subunits, and HPLC measurement of PIP metabolites. The effects of in vitro estrogen stimulation on LH-beta and PRL gene transcription is being studied in monolayer cultures of pituitary cells from old vs mature female rats.

自动灌注系统中垂体组织的持续研究 证实 GnRH 刺激的 LH 与年龄相关的下降的观察结果 分泌，之前在单层培养物中显示。逆转失败 GnRH 重复灌注脉冲引起的体外 LH 分泌不足 与我们之前在体内重复给药后的观察结果相似 GnRH 并进一步表明衰老与内在的 垂体促性腺激素分泌缺陷。小学最近的研究 异质垂体细胞悬液的单层培养揭示 给药后与年龄相关的 LH 分泌减少 佛波酯、PMA、蛋白激酶 C 激活剂以及之后 硝苯地平，一种电压门控钙通道阻滞剂。这些观察 表明 LH 释放的长期和短期刺激可能会持续进行 通过不同的机制，这些机制受到衰老的不同影响。 用于检查细胞、生化和分子的新技术 导致 LH 和 PRL 分泌与年龄相关的变化的事件 被引入我们实验室。这些包括；离心式 淘析、反溶血斑测定、免疫细胞化学和 免疫荧光、G 蛋白亚基的 RIA 和 PIP 的 HPLC 测量 代谢物。体外雌激素刺激对 LH-β 和 LH-β 的影响 正在垂体单层培养物中研究 PRL 基因转录 来自老年与成熟雌性大鼠的细胞。