Zieba D A, Amstalden M, Morton S, Gallino J L, Edwards J F, Harms P G, Williams G L
Animal Reproduction Laboratory, Texas A&M University Agricultural Research Station, Beeville, Texas 78102, USA.
J Endocrinol. 2003 Jul;178(1):83-9. doi: 10.1677/joe.0.1780083.
We have shown recently that leptin modulates at least two aspects of anterior pituitary LH release in ruminants: basal and GnRH-mediated release. To test the hypothesis that leptin directly affects basal and GHRH-mediated GH secretion from the adenohypophysis, we examined the effects of various doses of recombinant ovine leptin (oleptin) on perifused adenohypophyseal (AP) explants and compared responses of tIssues from control and fasted cows. Ten mature, ovariectomized and estradiol-implanted cows were assigned to one of two dietary groups: (1) normal-fed (n=5) and (2) fasted for 72 h (n=5). At the end of the fasting period, cows were euthanized and pituitaries were collected. Adenohypophyseal explants were perifused for a total of 6.5 h, including a 2-h treatment at 2.5 h with Krebs-Ringer bicarbonate buffer containing 0, 5, 10, 50, or 100 ng/ml oleptin, and a challenge with GHRH at 4.5 h. All doses of oleptin greater than 5 ng/ml decreased (P<0.01) basal GH secretion compared with controls in tIssues collected from normal-fed cows. In contrast, GH release from AP explants from fasted cows treated with the lowest dose of oleptin was 28% (P<0.002) higher than control explants, but larger doses had no effect. Leptin caused an inversely related, dose-dependent increase in GHRH-mediated GH release in tIssues from normal-fed cows. Marked increases (P<0.01-P<0.001) in GH release were observed for the 5 and 10 ng/ml oleptin, with lesser (P<0.08) and no effects observed at the 50 and 100 ng/ml doses respectively. In fasted cows, oleptin had no stimulatory effect on GHRH-induced GH release. Results show that leptin can act directly at the anterior pituitary level to modulate GH release, and this effect is dependent upon nutritional history.
我们最近发现,瘦素可调节反刍动物垂体前叶促黄体生成素释放的至少两个方面:基础释放和促性腺激素释放激素(GnRH)介导的释放。为了验证瘦素直接影响腺垂体基础和生长激素释放激素(GHRH)介导的生长激素(GH)分泌这一假设,我们研究了不同剂量的重组羊瘦素(oleptin)对灌流腺垂体(AP)外植体的影响,并比较了对照组和禁食奶牛组织的反应。将10头成熟、去卵巢并植入雌二醇的奶牛分为两个饮食组之一:(1)正常饲养(n = 5)和(2)禁食72小时(n = 5)。在禁食期结束时,对奶牛实施安乐死并采集垂体。腺垂体外植体总共灌流6.5小时,包括在2.5小时时用含0、5、10、50或100 ng/ml oleptin的 Krebs-Ringer碳酸氢盐缓冲液处理2小时,并在4.5小时时用GHRH进行刺激。与正常饲养奶牛采集的组织中的对照组相比,所有大于5 ng/ml的oleptin剂量均降低了(P<0.01)基础GH分泌。相比之下,用最低剂量oleptin处理的禁食奶牛的AP外植体的GH释放比对照外植体高28%(P<0.002),但更高剂量则无影响。瘦素使正常饲养奶牛组织中GHRH介导的GH释放呈剂量依赖性反向增加。对于5和10 ng/ml的oleptin,观察到GH释放显著增加(P<0.01 - P<0.001);对于50和100 ng/ml的剂量,分别观察到较小(P<0.08)和无影响。在禁食奶牛中,oleptin对GHRH诱导的GH释放无刺激作用。结果表明,瘦素可直接作用于垂体前叶水平来调节GH释放,且这种作用取决于营养史。