Developmental and sex-related changes of the growth hormone axis in lean and obese Zucker rats.
Developmental and sex-related changes of the growth hormone axis in lean and obese Zucker rats.
复制标题
瘦和肥胖 Zucker 大鼠生长激素轴的发育和性别相关变化。
DOI：
10.1159/000126362
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发表时间：
1993
影响因子：
4.1
通讯作者：
Millard,WJ
中科院分区：
文献类型：
--
作者：
LeidyJr,JW;Romano,TM;Millard,WJ
在 6 至 12 周龄的瘦和肥胖 Zucker 雄性和雌性大鼠中检查了下丘脑 - 垂体 GH 轴的发育和性别相关变化。 6 周时，任何表型/性别组的垂体 GH 含量均无差异。雄性大鼠的 GH 含量随着年龄的增长而增加，但在 10 周和 12 周时，相对于瘦大鼠，肥胖雄性大鼠的 GH 含量降低。雌性大鼠的GH含量没有增加，瘦和肥胖雌性大鼠的含量没有差异。各组之间下丘脑 GHRH 含量没有差异。与瘦雄性大鼠相比，肥胖雄性大鼠的下丘脑 SS 含量降低 (95%)，与瘦雌性大鼠相比，肥胖雌性大鼠的下丘脑 SS 含量降低 (78%)。 6-7 周龄大鼠的个体 6 小时血浆 GH 谱显示出特征性的两态性 GH 分泌模式。然而，与性别匹配的瘦大鼠相比，肥胖动物的自发 GH 分泌显着减少。肥胖雄性大鼠的 GH 峰值幅度（瘦肉的 25%）和平均 GH 浓度（瘦肉的 19%）降低，而 GH 峰值频率或基线水平没有显着变化。与瘦大鼠相比，肥胖雌性大鼠的 GH 峰值数量、峰值幅度、基线 GH 和平均 GH 浓度均下降。峰值幅度（瘦肉的 14%）和平均 GH 浓度（瘦肉的 20%）的减少与肥胖雄性大鼠的减少相似。 6 周时，各组之间的血清 IGF-I 浓度没有差异。雄性大鼠的 IGF-I 水平随着年龄的增长而增加，但瘦大鼠和肥胖大鼠之间没有差异。雌性大鼠中的 IGF-I 浓度随时间变化而变化，并且在瘦大鼠和肥胖大鼠之间没有差异。肥胖雄性和雌性大鼠的血清胰岛素在 6 至 12 周时有所增加。我们得出的结论是：(1) 肥胖雄性和雌性大鼠的 GH 分泌在 6-7 周时下降，下降幅度与之前在 12 周或以上雄性大鼠中观察到的情况相似； (2)仅在肥胖雄性大鼠中垂体GH含量降低，且发生在GH分泌缺陷后； (3)肥胖大鼠下丘脑GHRH含量无变化，下丘脑SS轻度至中度降低； (4)瘦大鼠和肥胖大鼠的血清IGF-I没有差异； (5)肥胖雄性和雌性大鼠均呈高胰岛素血症。这些观察结果表明 GH 分泌减少发生在 6-7 周或之前，并且先前观察到的 GH 轴的一些变化在 GH 分泌受损后继发发生。寻找 GH 分泌减少的机制应在 6-7 周或之前检查发育早期的 GH 轴。
The developmental and sex-related changes in the hypothalamic-pituitary GH axis were examined in lean and obese Zucker male and female rats from 6 to 12 weeks of age. Pituitary GH content was not different in any phenotype/sex group at 6 weeks. GH content increased with age in male rats, but at 10 and 12 weeks content was decreased in obese male rats relative to lean rats. GH content did not increase in female rats and there was no difference in content between lean and obese female rats. Hypothalamic GHRH content was not different between the groups. Hypothalamic SS content was decreased in obese male rats compared to lean male rats (95%) and in obese female rats compared to lean female rats (78%). Individual 6-hour plasma GH profiles from rats 6-7 weeks of age showed the characteristic sexually dimorphic GH secretory patterns. However, spontaneous GH secretion was dramatically reduced in obese animals when compared to sex-matched lean rats. GH peak amplitude (25% of lean) and mean GH concentration (19% of lean) were decreased in obese male rats without a significant alteration in GH peak frequency or baseline level. In obese female rats, the number of GH peaks, peak amplitude, baseline GH, and mean GH concentration were all decreased compared to lean. The reduction in peak amplitude (14% of lean) and in mean GH concentration (20% of lean) was similar to the reduction in obese male rats. Serum IGF-I concentrations were not different among the groups at 6 weeks. IGF-I levels in male rats increased with age but were not different between lean and obese rats. IGF-I concentrations in female rats were unchanged with time and were not different between lean and obese rats. Serum insulin was increased in obese male and female rats at 6 through 12 weeks. We conclude (1) GH secretion is depressed at 6-7 weeks in obese male and female rats with the magnitude of reduction similar to previous observations in male rats 12 weeks or older; (2) pituitary GH content is depressed only in obese male rats and occurs after the defect in GH secretion; (3) hypothalamic GHRH content is unchanged and hypothalamic SS is slightly to moderately decreased in obese rats; (4) serum IGF-I is not different between lean and obese rats; (5) obese male and female rats were hyperinsulinemic. These observations suggest that decreases in GH secretion occur at or before 6-7 weeks and that some previously observed changes in the GH axis occur secondarily after impaired GH secretion. The search for the mechanism of decreased GH secretion should examine the GH axis early in development on or before 6-7 weeks.