Chen C, Roh S G, Nie G Y, Loneragan K, Xu R W, Ruan M, Clarke L J, Goding J W, Gertler A
Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
Endocrine. 2001 Feb;14(1):73-8. doi: 10.1385/endo:14:1:073.
Although existing data suggest an influence of leptin on circulating levels of growth hormone (GH), the action site and properties of leptin are still controversial. Using primary cultured ovine pituitary cells, we studied the direct effect of leptin on the secretion of GH. Pituitary cells were dissociated by collagenase and subjected to Percoll gradient centrifugation to enrich the somatotroph population to 60-80% of cells. Treatment of primary cultured ovine somatotrophs with leptin (10(-9)-10(-7) M) for 30 min did not affect basal, GH-releasing hormone (GHRH) (10(-7) M)- or GH-releasing peptide-2 (GHRP-2)(10(-7) M)-stimulated GH secretion. Following treatment of cells for 1-3 d with leptin, GHRH-stimulated GH secretion was reduced and GHRP-2-stimulated GH secretion increased. The combined effect of GHRH and GHRP-2 on GH secretion was not altered by the treatment of cells with leptin for 3 d. GHRH receptor mRNA levels in cultured somatotrophs were decreased but GHRP receptor mRNA levels were increased by 3-d leptin treatment. These results suggest that leptin has a long-term effect on somatotrophs to reduce GHRH receptor synthesis leading to a decrease in GHRH-stimulated GH secretion. Leptin appears, however, to have an opposite effect on GHRP receptor synthesis leading to an increase in GHRP-stimulated GH secretion.
尽管现有数据表明瘦素对生长激素(GH)的循环水平有影响,但瘦素的作用位点和特性仍存在争议。我们使用原代培养的绵羊垂体细胞,研究了瘦素对GH分泌的直接影响。用胶原酶解离垂体细胞,并进行Percoll梯度离心,以使生长激素细胞群体富集至细胞总数的60 - 80%。用瘦素(10^(-9)-10^(-7) M)处理原代培养的绵羊生长激素细胞30分钟,并不影响基础状态、生长激素释放激素(GHRH)(10^(-7) M)或生长激素释放肽-2(GHRP-2)(10^(-7) M)刺激的GH分泌。用瘦素处理细胞1 - 3天后,GHRH刺激的GH分泌减少,而GHRP-2刺激的GH分泌增加。用瘦素处理细胞3天,并不改变GHRH和GHRP-2对GH分泌的联合作用。3天的瘦素处理可使培养的生长激素细胞中GHRH受体mRNA水平降低,但GHRP受体mRNA水平升高。这些结果表明,瘦素对生长激素细胞有长期作用,可减少GHRH受体合成,导致GHRH刺激的GH分泌减少。然而,瘦素对GHRP受体合成似乎有相反的作用,导致GHRP刺激的GH分泌增加。