Liu T C, Pu H F, Wang P S
Institute of Physiology, National Yang-Ming Medical College, Shih-Pai, Taipei, Taiwan, Republic of China.
Endocrinology. 1993 Mar;132(3):1189-94. doi: 10.1210/endo.132.3.8440179.
Delayed, attenuated, or absence of the proestrous LH surge occurs in aging rats. To assess how aging affects the positive feedback action of 17 beta-estradiol (E2) on the pituitary, we determined the responsiveness of rat pituitary cells to GnRH and the secretagogues affecting intracellular signal transduction mechanisms in the presence or absence of E2. We also correlated the LH response to pituitary LH content. Anterior pituitaries excised from ovariectomized Sprague-Dawley rats, either young (3-4 months) or old (19-20 months), were enzymatically dispersed and then pretreated with or without E2 (0.6 nM) for 48 h, followed by incubation for 3 h with or without various secretagogues. The secretagogues included GnRH (1 and 10 nM), veratridine (increases Ca2+ influx; 5 and 10 microM), and phorbol 12-myristate 13-acetate (a protein kinase-C activator; 10 and 100 nM). LH in media and cells were measured by RIA and expressed on the basis of cellular DNA. GnRH, veratridine, and phorbol 12-myristate 13-acetate at all doses stimulated (P < 0.01) LH release in cells from both young and old rats. E2 stimulated (P < 0.05 to P < 0.01) all secretagogue-induced LH release in cells from both young and old rats, but only basal LH release (P < 0.05) in cells from young rats. The magnitude of both basal and secretagogue-induced LH release in either the presence or absence of E2 was smaller (P < 0.01) in cells from old than in those from young rats. The initial cellular LH was lower (P < 0.01) in cells from old than in those from young rats. The LH-releasing ability (expressed as a percentage of total cellular LH) of cells from old rats was identical (P > 0.05) to that of cells from young rats under all conditions studied. These results suggest that the reduced magnitude of LH release by cells from old rats may be attributed to reduced cellular LH, rather than to impaired estrogen feedback or impaired signal transduction mechanisms. It remains to be determined whether LH biosynthesis per cell and/or the number of gonadotropes decrease with age.
衰老大鼠会出现发情前期促黄体生成素（LH）激增延迟、减弱或缺失的情况。为了评估衰老如何影响17β-雌二醇（E2）对垂体的正反馈作用，我们测定了大鼠垂体细胞对促性腺激素释放激素（GnRH）以及影响细胞内信号转导机制的促分泌素在有无E2存在时的反应性。我们还将LH反应与垂体LH含量进行了关联。从年轻（3 - 4个月）或年老（19 - 20个月）的去卵巢Sprague-Dawley大鼠中切除垂体前叶，酶解分散后，用或不用E2（0.6 nM）预处理48小时，然后用或不用各种促分泌素孵育3小时。促分泌素包括GnRH（1和10 nM）、藜芦碱（增加Ca2+内流；5和10 μM）以及佛波酯12-肉豆蔻酸酯13-乙酸酯（一种蛋白激酶C激活剂；10和100 nM）。通过放射免疫分析法（RIA）测定培养基和细胞中的LH，并以细胞DNA为基础进行表达。所有剂量的GnRH、藜芦碱和佛波酯12-肉豆蔻酸酯13-乙酸酯均刺激（P < 0.01）年轻和年老大鼠细胞中的LH释放。E2刺激（P < 0.05至P < 0.01）年轻和年老大鼠细胞中所有促分泌素诱导的LH释放，但仅刺激年轻大鼠细胞中的基础LH释放（P < 0.05）。在有或无E2的情况下，年老大鼠细胞中基础和促分泌素诱导的LH释放幅度均小于（P < 0.01）年轻大鼠细胞。年老大鼠细胞中的初始细胞内LH低于（P < 0.01）年轻大鼠细胞。在所有研究条件下，年老大鼠细胞的LH释放能力（以细胞总LH的百分比表示）与年轻大鼠细胞相同（P > 0.05）。这些结果表明，年老大鼠细胞中LH释放幅度降低可能归因于细胞内LH减少，而非雌激素反馈受损或信号转导机制受损。每个细胞的LH生物合成和/或促性腺激素细胞数量是否随年龄减少仍有待确定。
