Cuttler L, Collins B J, Szabo M
Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio 44106, USA.
J Endocrinol. 1995 May;145(2):307-14. doi: 10.1677/joe.0.1450307.
GH secretory patterns undergo marked change during early mammalian development. The factors that underlie these changes and the major components of signal transduction in the immature somatotrophs are not fully understood. Increasing evidence suggests that protein kinase C (PKC) plays a central role in perinatal organ differentiation and function. To evaluate the possible role of PKC as a mediator of GH secretion from immature pituitaries, we tested the effects of the PKC activating phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), alone or together with GH-releasing factor (GRF), somatostatin (SRIF), and Ca2+ modifying agents; an inactive phorbol analogue (4 alpha-12-13-didecanoate; 4 alpha-PDD), and phospholipase C on GH release from pituitary cell cultures from perinatal and mature rats. Pituitary primary cell cultures were prepared from fetal (day 20 of 21.5 days of gestation), 2-day-old, 12-day-old, and adult male (2- to 4-month-old) rats. Each experiment was performed on at least three separate occasions. The magnitude of TPA (0.15-150 nM)-induced GH release was markedly age-dependent, fractional GH release being greatest from pituitaries of fetal and newborn rats, and least from those of adults (P < 0.001). Further, the minimum dose of TPA required to stimulate GH release over basal levels was tenfold higher for adult pituitaries (15 nM) than for perinatal pituitaries (1.5 nM). Phospholipase C (1 and 10 U/ml) also caused greater fractional GH release from neonatal pituitaries than from adult pituitaries (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
在哺乳动物早期发育过程中，生长激素（GH）的分泌模式会发生显著变化。导致这些变化的因素以及未成熟生长激素细胞中信号转导的主要成分尚未完全明确。越来越多的证据表明，蛋白激酶C（PKC）在围产期器官分化和功能中起着核心作用。为了评估PKC作为未成熟垂体GH分泌介质的可能作用，我们测试了PKC激活剂佛波酯12 - O - 十四酰佛波醇 - 13 - 乙酸酯（TPA）单独或与生长激素释放因子（GRF）、生长抑素（SRIF）以及钙离子调节剂共同作用的效果；一种无活性的佛波类似物（4α - 12 - 13 - 二癸酸酯；4α - PDD）以及磷脂酶C对围产期和成年大鼠垂体细胞培养物中GH释放的影响。垂体原代细胞培养物取自胎儿（妊娠21.5天中的第20天）、2日龄、12日龄以及成年雄性（2至4月龄）大鼠。每个实验至少在三个不同的时间进行。TPA（0.15 - 150 nM）诱导的GH释放幅度明显依赖于年龄，胎儿和新生大鼠垂体的GH释放分数最高，成年大鼠垂体的最低（P < 0.001）。此外，刺激GH释放超过基础水平所需的TPA最小剂量，成年垂体（15 nM）是围产期垂体（1.5 nM）的十倍。磷脂酶C（1和10 U/ml）也导致新生垂体的GH释放分数高于成年垂体（P <
0.01）。（摘要截断于250字）
