Nieves-Rivera F, Kerrigan J R, Krieg R J, Egan J, Hwang L J, Truumees E, Veldhuis J D, Evans W S, Rogol A D
Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville 22908.
Growth Regul. 1993 Dec;3(4):235-44.
Diminished concentrations of growth hormone (GH) have been observed in the male BB/Wor rat with diabetes mellitus (DM). The precise mechanism(s) responsible for the altered GH levels is not entirely understood. We have therefore employed independent techniques to investigate potential alterations in: 1) the peripheral metabolism of the hormone; 2) GH release by somatotropes; and 3) hypothalamic regulation of GH secretion. An extra group of insulin-untreated animals was included for the studies of acute DM. The results demonstrate diminished circulating mean concentrations of GH (35 +/- 4 vs. 16 +/- 4 micrograms/l; mean +/- SEM; control vs. animal with DM; P = 0.006) due to impaired GH secretion. In particular, there was a decrease in the mass of GH secreted per burst (230 +/- 22 vs. 136 +/- 34 micrograms/l; P = 0.04) and in the GH secretory rate (24 +/- 4 vs. 9 +/- 3 micrograms/l/min; P < 0.01). No differences in the secretory burst frequency, (5.3 +/- 0.3 vs. 5.2 +/- 0.5 #/8-h; P = 0.68), secretory half-duration (10 +/- 2 vs. 17 +/- 2 min; P = 0.09), or serum GH half-life (8 +/- 1 vs. 6 +/- 1 min; P = 0.13) were observed. In vitro studies of acutely dispersed somatotropes obtained from rats with DM demonstrated increased sensitivity to GHRH (1 nM), as detected by a greater mean hemolytic plaque area following exposure to an EC50 dose of the secretagogue (14.3 +/- 3.3 vs. 17.4 +/- 3.5 microns 2 x 10(3); P = 0.049), and diminished sensitivity to SRIH (1 nM) inhibition of GH release following exposure to an EC50 dose of the secretagogue (10.0 +/- 1.2 vs. 14.9 +/- 2.3 microns2 x 10(3); P = 0.026). The number of the pituitary cells (18.0 +/- 2.8 vs. 15.3 +/- 1.0 x 10(5) cells; P = 0.38) as well as the number of somatotropes (7.3 +/- 1.4 vs. 7.6 +/- 0.9 x 10(5) cells; P = 0.87) were indistinguishable between experimental groups. Hypothalamic gene transcript levels for GH-releasing hormone (GHRH) and somatotropin release-inhibiting hormone (SRIH) were evaluated by in situ hybridization histochemistry to assess cellular synthetic activity.(ABSTRACT TRUNCATED AT 400 WORDS)
在患有糖尿病（DM）的雄性BB/Wor大鼠中，已观察到生长激素（GH）浓度降低。导致GH水平改变的确切机制尚未完全明确。因此，我们采用了独立的技术来研究以下方面的潜在变化：1）激素的外周代谢；2）生长激素细胞释放GH；3）下丘脑对GH分泌的调节。另外纳入一组未接受胰岛素治疗的动物用于急性DM的研究。结果表明，由于GH分泌受损，循环中GH的平均浓度降低（35±4 vs. 16±4微克/升；平均值±标准误；对照组 vs. DM动物；P = 0.006）。特别是，每次脉冲分泌的GH量减少（230±22 vs. 136±34微克/升；P = 0.04），GH分泌率降低（24±4 vs. 9±3微克/升/分钟；P < 0.01）。在分泌脉冲频率（5.3±0.3 vs. 5.2±0.5次/8小时；P = 0.68）、分泌半衰期（10±2 vs. 17±2分钟；P = 0.09）或血清GH半衰期（8±1 vs. 6±1分钟；P = 0.13）方面未观察到差异。对从DM大鼠获得的急性分散生长激素细胞进行的体外研究表明，对生长激素释放激素（GHRH，1 nM）的敏感性增加，这可通过在暴露于促分泌剂的半数有效剂量（EC50）后更大的平均溶血空斑面积检测到（14.3±3.3 vs. 17.4±3.5微米2×10³；P = 0.049），并且在暴露于促分泌剂的EC50剂量后，对生长抑素（SRIH，1 nM）抑制GH释放的敏感性降低（10.0±1.2 vs. 14.9±2.3微米2×10³；P = 0.026）。实验组之间垂体细胞数量（18.0±2.8 vs. 15.3±1.0×10⁵个细胞；P = 0.38）以及生长激素细胞数量（7.3±1.4 vs. 7.6±0.9×10⁵个细胞；P = 0.87）没有差异。通过原位杂交组织化学评估下丘脑生长激素释放激素（GHRH）和生长激素释放抑制激素（SRIH）的基因转录水平，以评估细胞合成活性。（摘要截断于400字）
