Torronteras R, Gracia-Navarro F, Elsaesser F
Division of Endocrinology, Institute of Animal Husbandry and Animal Behaviour (FAL), Mariensee, Germany.
Neuroendocrinology. 1997 Feb;65(2):117-28. doi: 10.1159/000127171.
The physiological mechanism underlying the enormously elevated fetal plasma GH concentrations in mammalian species is not well understood. We postulated that a decreased sensitivity to the inhibitory effects of somatostatin (SRIH) and insulin-like growth factor-1 (IGF-1) at the pituitary level during porcine fetal life might be one factor in the high plasma GH levels. Therefore, the acute effects of GH-releasing hormone (GHRH), SRIH, and IGF-1 on GH release from the porcine anterior pituitary (AP) were studied using a perifusion system. AP tissue pieces from male and female fetuses (95 days postcoitum) and piglets (10-12 days postpartum) were perifused (at least 6 replicates per treatment and sex) at a rate of 0.1 ml/min and fractions were collected at 10-min intervals. Tissue was subjected to various treatments in random order: a 10-min GHRH pulse (1 nM) with or without concomitant 40-min exposure to SRIH (1, 10 or 100 nM) or IGF-1 (1 or 10 nM) or exposure to SRIH or IGF-1 alone (10 nM each). None of the treatments revealed sex differences, therefore data from males and females were pooled. Exposure to GHRH resulted in a rapid stimulatory GH response both in fetuses (from 61.1 +/- 4.1 to 125.6 +/- 4.7 ng GH.80 min-1.mg-1 AP, p < 0.05) and neonates (from 58.1 +/- 5.3 to 104.6 +/- 4.5 ng GH.80 min-1.mg-1 AP, p < 0.05). Exposure to the lowest dose of SRIH or IGF-1 (1 nM) during GHRH pulse inhibited (p < 0.05) the GH response to GHRH in neonates (74.3 +/- 3.9 and 72.5 +/- 6.3 ng GH.80 min-1.mg-1 AP, respectively), but not in fetuses (115.9 +/- 5.8 and 118.7 +/- 5.4 ng GH.80 min-1.mg-1 AP, respectively). When high doses of SRIH (10 or 100 nM) or IGF-1 (10 nM) were used, the GHRH-induced GH release was totally blocked in neonates (p < 0.05). However, in fetuses the GH response was inhibited only during the first 40 min after GHRH, and a rebound or delay effect occurred during the next 40 min. Irrespective of these general findings, some individual profiles from fetuses (4 profiles) showed that 1 nM SRIH or IGF-1 could inhibit GHRH-induced GH secretion. In contrast, individual profiles from neonates indicated that high doses of SRIH (7 profiles) or IGF-1 (5 profiles) were unable to block GH release stimulated by GHRH. On the other hand, a paradoxical stimulation of GH was observed during treatment with SRIH alone in three individual profiles from fetuses. These data confirm our hypothesis that the highly elevated plasma GH levels in the porcine fetus in vivo (compared to neonates) may be explained, at least in part, by a decreased sensitivity to the inhibitory effects of SRIH and IGF-1 at the pituitary level during fetal life. Results from some profiles indicated individual variations in the maturation of the GH control system, and moreover, even a 'paradoxical' enhancement of GH release in some fetal GH profiles.
哺乳动物胎儿血浆生长激素（GH）浓度大幅升高背后的生理机制尚未完全明确。我们推测，猪胎儿期垂体水平对生长抑素（SRIH）和胰岛素样生长因子-1（IGF-1）抑制作用的敏感性降低可能是血浆GH水平升高的一个因素。因此，我们使用灌流系统研究了生长激素释放激素（GHRH）、SRIH和IGF-1对猪垂体前叶（AP）GH释放的急性影响。以0.1 ml/min的流速对雄性和雌性胎儿（妊娠95天）及仔猪（出生后10 - 12天）的AP组织块进行灌流（每种处理和性别至少6次重复），每隔10分钟收集一次馏分。组织按随机顺序接受不同处理：10分钟的GHRH脉冲（1 nM），同时或不同时伴有40分钟的SRIH（1、10或100 nM）或IGF-1（1或10 nM）暴露，或单独暴露于SRIH或IGF-1（各10 nM）。所有处理均未显示出性别差异，因此将雄性和雌性的数据合并。暴露于GHRH会使胎儿（从61.1±4.1至125.6±4.7 ng GH·80 min⁻¹·mg⁻¹ AP，p < 0.05）和新生儿（从58.1±5.3至104.6±4.5 ng GH·80 min⁻¹·mg⁻¹ AP，p < 0.05）的GH迅速产生刺激反应。在GHRH脉冲期间暴露于最低剂量的SRIH或IGF-1（1 nM）会抑制（p < 0.05）新生儿对GHRH的GH反应（分别为74.3±3.9和72.5±6.3 ng GH·80 min⁻¹·mg⁻¹ AP），但对胎儿无此作用（分别为115.9±5.8和118.7±5.4 ng GH·80 min⁻¹·mg⁻¹ AP）。当使用高剂量的SRIH（10或100 nM）或IGF-1（10 nM）时，GHRH诱导的GH释放在新生儿中被完全阻断（p < 0.05）。然而，在胎儿中，GH反应仅在GHRH后的前40分钟受到抑制，随后40分钟出现反弹或延迟效应。尽管有这些总体发现，但一些胎儿的个体情况（4例）显示，1 nM SRIH或IGF-1可抑制GHRH诱导的GH分泌。相反，新生儿的个体情况表明，高剂量的SRIH（7例）或IGF-1（5例）无法阻断GHRH刺激的GH释放。另一方面，在来自胎儿的三个个体情况中，单独使用SRIH处理期间观察到了GH的反常刺激。这些数据证实了我们的假设，即猪胎儿体内血浆GH水平的高度升高（与新生儿相比），至少部分可以通过胎儿期垂体水平对SRIH和IGF-1抑制作用的敏感性降低来解释。一些个体情况的结果表明GH控制系统成熟存在个体差异，此外，在一些胎儿的GH情况中甚至出现了GH释放的“反常增强”。
