Ceda G P, Valenti G, Butturini U, Hoffman A R
Endocrinology. 1986 May;118(5):2109-14. doi: 10.1210/endo-118-5-2109.
The pattern of GH secretion undergoes substantial changes in the aging rat, resulting in decreased daily secretion of GH. In this study, the pituitary responsiveness to GH-releasing factor (GRF) was examined in young (2- to 5-month old) and aging (14- to 18-month old) male rats. In vivo studies were performed under sodium pentobarbital anesthesia. After injection of 250 ng GRF/100 g BW, young rats experienced more GH secretion [peak level, 544.5 +/- 209.5 (+/- SEM) ng/ml] than did 18-month-old rats (89.3 +/- 13.7 ng/ml). To investigate the locus of this insensitivity to GRF, anterior pituitary cells from young and aging rats were dispersed and placed in primary culture. While basal GH secretion from the cultured pituitary cells was similar in the two groups (49.7 +/- 3.5 vs. 47.8 +/- 2.7 ng/ml X 4 h for the 2- and 18-month old rats, respectively), the GH-releasing ability of GRF was partially but significantly impaired in cells derived from both 14- and 18-month old rats; 100 nM GRF stimulated the release of 96.7 +/- 1.8 ng/ml X 4 h in the 18-month old rats as opposed to 115.0 +/- 6.0 (P less than 0.05) ng/ml X 4 h in the 2-month-old rats. Since GRF stimulates GH release through the activation of adenylate cyclase, intracellular cAMP levels were measured in the cultured pituitary cells. GRF stimulated 65% less intracellular cAMP accumulation in the 18-month-old rats. In 14-month-old rats, the ability of forskolin and (Bu)2 cAMP to release GH was impaired, while phorbol ester-elicited GH secretion was unchanged. In conclusion, the GH response to GRF is blunted in aging rats. While much of the insensitivity to GRF may be mediated by the increased somatostatin tone reported in aging rats, a diminished pituitary cAMP response to GRF may also be an important etiological factor in the hyposomatotropinemia of the aging male rat.
在衰老的大鼠中，生长激素（GH）的分泌模式发生了显著变化，导致GH的每日分泌量减少。在本研究中，检测了年轻（2至5月龄）和衰老（14至18月龄）雄性大鼠垂体对生长激素释放因子（GRF）的反应性。体内研究在戊巴比妥钠麻醉下进行。注射250 ng GRF/100 g体重后，年轻大鼠的GH分泌量[峰值水平，544.5±209.5（±标准误）ng/ml]比18月龄大鼠（89.3±13.7 ng/ml）更多。为了研究对GRF不敏感的部位，将年轻和衰老大鼠的垂体前叶细胞分散并进行原代培养。虽然两组培养的垂体细胞基础GH分泌相似（2月龄和18月龄大鼠分别为49.7±3.5与47.8±2.7 ng/ml×4小时），但来自14月龄和18月龄大鼠的细胞中GRF释放GH的能力部分但显著受损；100 nM GRF在18月龄大鼠中刺激4小时释放96.7±1.8 ng/ml，而在2月龄大鼠中为115.0±6.0（P<0.05）ng/ml×4小时。由于GRF通过激活腺苷酸环化酶刺激GH释放，因此在培养的垂体细胞中测量了细胞内cAMP水平。GRF在18月龄大鼠中刺激的细胞内cAMP积累减少了65%。在14月龄大鼠中，福斯可林和（Bu）2 cAMP释放GH的能力受损，而佛波酯诱导的GH分泌未改变。总之，衰老大鼠对GRF的GH反应减弱。虽然对GRF的许多不敏感可能是由衰老大鼠中报道的生长抑素水平升高介导的，但垂体对GRF的cAMP反应减弱也可能是衰老雄性大鼠生长激素缺乏血症的一个重要病因因素。
