Nagatani S, Zeng Y, Keisler D H, Foster D L, Jaffe C A
Reproductive Sciences Program, University of Michigan, Ann Arbor 48109, USA.
Endocrinology. 2000 Nov;141(11):3965-75. doi: 10.1210/endo.141.11.7762.
Administration of leptin during reduced nutrition improves reproductive activity in several monogastric species and reverses GH suppression in rodents. Whether leptin is a nutritional signal regulating neuroendocrine control of pituitary function in ruminant species is unclear. The present study examined the control of pulsatile LH and GH secretion in sheep. We determined whether exogenous leptin could prevent either the suppression of pulsatile LH secretion or the enhancement of GH secretion that occur during fasting. Recombinant human met-leptin (rhmet-leptin; 50 microg/kg BW; n = 8) or vehicle (n = 7) was administered s.c. every 8 h during a 78-h fast to estrogen-treated, castrated yearling males. LH and GH were measured in blood samples collected every 15 min for 6 h before fasting and during the last 6 h of fasting. Leptin was measured both by a universal leptin assay and by an assay specific for ovine leptin. During the fast, endogenous plasma leptin fell from 1.49 +/- 0.16 to 1.03 +/- 0.13 ng/ml. The average concentration of rhmet-leptin 8 h after leptin administration was 18.0 ng/ml. During fasting, plasma insulin, glucose, and insulin-like growth factor I levels declined, and nonesterified fatty acid concentrations increased similarly in vehicle-treated and leptin-treated animals. In vehicle-treated animals, LH pulse frequency declined markedly during fasting (5.6 +/- 0.5 vs. 1.1 +/- 0.5 pulses/6 h; fed vs. fasting; P < 0.0001). Leptin treatment prevented the fall in LH pulse frequency (5.0 +/- 0.4 vs. 4.9 +/- 0.4 pulses/6 h; P = 0.6). Neither fasting nor leptin administration altered GH pulse frequency. Fasting produced a modest increase in mean concentrations of circulating GH in control animals (2.4 +/- 0.5 vs. 3.4 +/- 0.6 ng/ml; P = 0.04), whereas there was a much greater increase in GH during leptin treatment (2.7 +/- 0.6 vs. 8.6 +/- 1.6 ng/ml; P = 0.0001). GH pulse amplitudes were also increased by fasting in control (P = 0.04) and leptin-treated sheep (P = 0.007). The finding that exogenous rhmet-leptin regulates LH and GH secretion in sheep indicates that this fat-derived hormone conveys information about nutrition to mechanisms controlling neuroendocrine function in ruminants.
在营养减少期间给予瘦素可改善几种单胃动物的生殖活动，并逆转啮齿动物中生长激素（GH）的抑制。瘦素是否作为一种营养信号调节反刍动物垂体功能的神经内分泌控制尚不清楚。本研究检测了绵羊中促黄体生成素（LH）和GH的脉冲式分泌调控。我们确定外源性瘦素是否能预防禁食期间发生的LH脉冲式分泌抑制或GH分泌增强。在78小时禁食期间，对经雌激素处理的去势一岁雄性绵羊每8小时皮下注射重组人甲硫氨酸瘦素（rhmet-瘦素；50微克/千克体重；n = 8）或赋形剂（n = 7）。在禁食前6小时和禁食最后6小时期间，每15分钟采集一次血样，检测LH和GH。通过通用瘦素测定法和绵羊瘦素特异性测定法检测瘦素。禁食期间，内源性血浆瘦素从1.49±0.16降至1.03±0.13纳克/毫升。给予瘦素8小时后，rhmet-瘦素的平均浓度为18.0纳克/毫升。禁食期间，在给予赋形剂处理和瘦素处理的动物中，血浆胰岛素、葡萄糖和胰岛素样生长因子I水平均下降，非酯化脂肪酸浓度的增加相似。在给予赋形剂处理的动物中，禁食期间LH脉冲频率显著下降（5.6±0.5对1.1±0.5次脉冲/6小时；进食对禁食；P < 0.0001）。瘦素处理可防止LH脉冲频率下降（5.0±0.4对4.9±0.4次脉冲/6小时；P = 0.6）。禁食和给予瘦素均未改变GH脉冲频率。禁食使对照动物循环GH的平均浓度略有增加（2.4±0.5对3.4±0.6纳克/毫升；P = 0.04），而在瘦素处理期间GH增加幅度更大（2.7±0.6对8.6±1.6纳克/毫升；P = 0.0001）。禁食也使对照（P = 0.04）和瘦素处理的绵羊（P = 0.007）的GH脉冲幅度增加。外源性rhmet-瘦素调节绵羊LH和GH分泌这一发现表明，这种脂肪衍生激素将营养信息传递给反刍动物中控制神经内分泌功能的机制。
