Ezzat S, Laks D, Oster J, Melmed S
Division of Endocrinology and Metabolism, Cedars-Sinai Medical Center-University of California School of Medicine, Los Angeles 90048.
Endocrinology. 1991 Feb;128(2):937-43. doi: 10.1210/endo-128-2-937.
GH is first detectable in the fetal rat pituitary between gestational days 18 and 19. The reasons for the GH surge soon after birth and subsequent postnatal decline to adult levels remain unclear. We therefore determined whether GH gene regulation in the developing pituitary could be distinguished from adult rat somatotroph function. In primary cultures of fetal and neonatal rat pituitary cells, GH secretion was detected by the 20th gestational day. These cells were stimulated by GH-releasing hormone (GHRH), but not by T3 or the morphogen retinoic acid. The stimulatory effect of T3 (0.25 mM) on GH secretion was detected only on the 2nd neonatal day and was similar to that seen in mature rat pituitary cell cultures. GHRH (10 nM) treatment for 24 h caused a 5-fold induction of GH secretion in pituitary cells derived from 2-, 5-, and 12-day-old neonatal rats. The presence or absence of T3 in the culture medium did not alter the response to GHRH. In contrast, only 2-fold induction of GH was observed in adult male pituitary cells during the same time course. Insulin-like growth factor-I (IGF-I; 6.5 nM), the peripheral target hormone for GH, resulted in a modest (20%) attenuation of GH secretion from pituitary cells derived from 20-day-old fetuses. IGF-I, however, produced a 70% reduction in GH levels in adult male pituitary cells grown under similar conditions. The effects of IGF-I on adult pituitary cells grown in T3-depleted medium were blunted. Addition of T3 partially restored the responsiveness of these cells to IGF-I. The results suggest that the high circulating GH levels in the fetal and neonatal rat may be secondary to relative insensitivity of the immature somatotroph to the inhibitory actions of IGF-I in addition to enhanced responsiveness to GHRH compared with the adult rat pituitary. Relative thyroid hormone deficiency in the immature rat may be contributory to this early transient state of pituitary IGF-I resistance.
生长激素（GH）最早在妊娠第18至19天的胎鼠垂体中被检测到。出生后不久GH激增以及随后产后降至成年水平的原因仍不清楚。因此，我们确定发育中的垂体中GH基因调控是否与成年大鼠生长激素细胞功能有所不同。在胎鼠和新生鼠垂体细胞的原代培养中，在妊娠第20天检测到了GH分泌。这些细胞受到生长激素释放激素（GHRH）的刺激，但不受T3或形态发生素视黄酸的刺激。仅在新生第2天检测到T3（0.25 mM）对GH分泌的刺激作用，且与成熟大鼠垂体细胞培养中的情况相似。用GHRH（10 nM）处理24小时可使来自2日龄、5日龄和12日龄新生大鼠的垂体细胞中的GH分泌增加5倍。培养基中T3的存在与否不会改变对GHRH的反应。相比之下，在相同时间进程中，成年雄性垂体细胞中仅观察到GH分泌增加2倍。胰岛素样生长因子-I（IGF-I；6.5 nM）是GH的外周靶激素，可使来自20日龄胎儿的垂体细胞的GH分泌适度减少（20%）。然而，IGF-I使在相似条件下培养的成年雄性垂体细胞中的GH水平降低了70%。IGF-I对在缺乏T3的培养基中生长的成年垂体细胞的作用减弱。添加T3可部分恢复这些细胞对IGF-I的反应性。结果表明，胎鼠和新生鼠中循环GH水平较高可能是由于未成熟的生长激素细胞对IGF-I的抑制作用相对不敏感，此外与成年大鼠垂体相比，对GHRH的反应性增强。未成熟大鼠中相对甲状腺激素缺乏可能促成了垂体IGF-I抵抗的这种早期短暂状态。
