生长激素释放因子、生长抑素和胰岛素样生长因子I对绵羊胎儿和新生垂体细胞体外生长激素（GH）分泌的调节

Regulation of growth hormone (GH) secretion by GH-releasing factor, somatostatin, and insulin-like growth factor I in ovine fetal and neonatal pituitary cells in vitro.

作者信息

Silverman B L, Bettendorf M, Kaplan S L, Grumbach M M, Miller W L

机构信息

Department of Pediatrics, University of California, San Francisco 94143.

出版信息

Endocrinology. 1989 Jan;124(1):84-9. doi: 10.1210/endo-124-1-84.

DOI:10.1210/endo-124-1-84

PMID:2562828

Abstract

Serum GH concentrations in the ovine fetus are much higher than those in the neonate, and the maximal GH response induced by GRF is 5-fold greater in the fetus than in the neonate. To clarify these in vivo observations further, we studied the effects of GRF, somatostatin (SRIF), and insulin-like growth factor I (IGF-I) on primary cultures of fetal and neonatal ovine pituitary cells. GH secretion from fetal ovine pituitary cells increased from 148 +/- 34 to 950 +/- 130 ng/10(5) cells.3 h in response to 1 nM GRF, whereas GH secretion from neonatal pituitary cells rose from 113 +/- 26 to 1221 +/- 129 ng/10(5) cells.3 h, a significantly greater response (P less than 0.001). This greater GRF-induced GH response in neonatal than fetal cells differs from the response in vivo and suggests that the increased in vivo response in the fetus is not due to inherently increased sensitivity of pituitary cells to GRF. SRIF (10 nM) decreased maximal GRF-induced GH secretion by 37 +/- 3% in fetal cells compared with 59 +/- 8% in neonatal cells (P less than 0.01). This may explain in part the decreased in vivo sensitivity to SRIF in the ovine fetus compared to that in the neonatal lamb. In fetal pituitary cells, 10 nM GRF increased ovine (o) GH mRNA from 100 +/- 14% to 145 +/- 40%, SRIF decreased oGH mRNA to 84 +/- 3%, and GRF and SRIF in combination increased fetal oGH mRNA to 126 +/- 24%. Values in neonatal pituitary cell cultures were similar (control, 100 +/- 17%; GRF, 132 +/- 6%, SRIF, 85 +/- 15%; GRF plus SRIF, 105 +/- 26%). Pretreating fetal cells with 100 nM IGF-I for 3 days reduced GRF-stimulated GH secretion from 1049 +/- 38 to 232 +/- 8 ng/10(5) cells.3 h (P less than 0.001). Similarly, IGF-I pretreatment of neonatal cells reduced GRF-stimulated GH secretion from 810 +/- 18 to 419 +/- 16 ng/10(5) cells.3 h (P less than 0.001). The mean secreted IGF-I was 0.58 U/ml (36 nM) in culture medium from neonatal cells and was unchanged by incubation for 3 days with 5 micrograms/ml hGH. Secreted IGF-I in medium from fetal cells was 0.87 U/ml (54 nM) without GH and 0.81 U/ml (51 nM) after incubation with human GH. IGF-I mRNA was present in neonatal pituitary and brain.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

绵羊胎儿血清生长激素（GH）浓度远高于新生儿，且生长激素释放因子（GRF）诱导的最大GH反应在胎儿中比新生儿大5倍。为进一步阐明这些体内观察结果，我们研究了GRF、生长抑素（SRIF）和胰岛素样生长因子I（IGF-I）对绵羊胎儿和新生儿垂体细胞原代培养物的影响。绵羊胎儿垂体细胞的GH分泌在1 nM GRF刺激下，从148±34 ng/10⁵细胞增加到950±130 ng/10⁵细胞·3小时，而新生儿垂体细胞的GH分泌从113±26 ng/10⁵细胞增加到1221±129 ng/10⁵细胞·3小时，反应显著更大（P<0.001）。新生儿细胞中这种GRF诱导的GH反应比胎儿细胞更大，这与体内反应不同，表明胎儿体内反应增加并非由于垂体细胞对GRF的固有敏感性增加。10 nM SRIF使胎儿细胞中GRF诱导的最大GH分泌减少37±3%，而新生儿细胞中减少59±8%（P<0.01）。这可能部分解释了与新生羔羊相比，绵羊胎儿对SRIF的体内敏感性降低。在胎儿垂体细胞中，10 nM GRF使绵羊（o）GH mRNA从100±14%增加到145±40%，SRIF使oGH mRNA降至84±3%，GRF和SRIF联合使用使胎儿oGH mRNA增加到126±24%。新生儿垂体细胞培养物中的值相似（对照，100±17%；GRF，132±6%，SRIF，85±15%；GRF加SRIF，105±26%）。用100 nM IGF-I预处理胎儿细胞3天，使GRF刺激的GH分泌从1049±38 ng/10⁵细胞·3小时降至232±8 ng/10⁵细胞·3小时（P<0.001）。同样，IGF-I预处理新生儿细胞使GRF刺激的GH分泌从810±18 ng/10⁵细胞·3小时降至419±16 ng/10⁵细胞·3小时（P<0.