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

激素与衰老——实验动物的垂体和下丘脑功能

• 批准号: 3823126
• 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/3823126
• 关键词: Leydig cells; aging; animal age group; animal old age; cyclic AMP; density gradient ultracentrifugation; dopamine; electron microscopy; estrogens; follicle stimulating hormone; free radicals; histochemistry /cytochemistry; hormone regulation /control mechanism; hypothalamus; immunochemistry; ionophores; luteinizing hormone; male castration; mature animal; pituitary gland; pituitary gonadal axis; prolactin; radioimmunoassay; superoxides; thyrotropin; tissue /cell culture

Isolated cells from rat anterior pituitary glands are studied in vitro to compare their physiology in old vs. mature male and female rats. Production of TSH, prolactin, and gonadotropins (LH and FSH) are studied after treatment with specific stimulatory and inhibitory compounds, included TRH, LHRH, estrogen, dopamine, and iontophores. Deranged and altered function of aged rat pituitary cells in vitro has been found. Pretreatment of old and young rats for up to 24 hours with pulsatile doses of LHRH does not restore function of cells derived from old rats to levels observed for younger animals. Similarly, enhanced tranmembrane transport of calcium ion with iontophore A23187 does not reverse the age-related defect in LH secretion. Data support our prior results suggesting an intrinsic age-related derangement in pituitary gonadotropic function. We have also described enhanced basal and estrogen stimulated Prl secretion by pituitary cells from old female rats, an increase in function disproportionate to the smaller increase in lactotrope number in aging rat pituitary glands. We have begun an investigation of the role of oxygen free radicals in the phenomenon of "in vitro" aging of Leydig (testosterone- secreting) cells. Preliminary experiments have demonstrated isolated Leydig cells to have lower activity of the protective enzyme, copper-zinc superoxide dismutase, than cells derived from seminiferous tubules, which normally surround (and may protect) Leydig cells from superoxide damage in vivo.

在体外研究了从大鼠垂体前叶腺分离的细胞， 比较它们在老年与成熟的雄性和雌性大鼠中的生理学。 研究促甲状腺激素、催乳素和促性腺激素（LH和FSH）的产生 在用特异性刺激和抑制化合物处理后， 包括TRH、LHRH、雌激素、多巴胺和离子通道。 疯狂和 在体外实验中发现老年大鼠垂体细胞的功能改变。 用脉冲剂量预处理老年和年轻大鼠长达24小时 LHRH不能恢复来自老年大鼠的细胞的功能， 观察年轻的动物。 类似地，增强的跨膜转运 钙离子与离子载体A23187的作用并不能逆转与年龄相关的 LH分泌缺陷。 数据支持我们先前的结果，表明 垂体促性腺激素功能内在年龄相关紊乱 我们 也描述了通过以下方式增强基础和雌激素刺激的Prl分泌： 老年雌性大鼠的垂体细胞， 与衰老大鼠中催乳素数量的较小增加不成比例 脑下垂体 我们已经开始研究氧气的作用 睾丸间质“体外”老化现象中的自由基 （睾酮分泌）细胞。 初步实验表明， 分离的Leydig细胞具有较低的保护酶活性， 铜锌超氧化物歧化酶，比来自生精细胞 小管，通常包围（并可能保护）Leydig细胞， 体内超氧化物损伤。