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雄性和雌性大鼠中阿片类物质介导的生殖内分泌控制的个体发生。

Ontogeny of the opioid-mediated control of reproductive endocrinology in the male and female rat.

作者信息

Cicero T J, Schmoeker P F, Meyer E R, Miller B T, Bell R D, Cytron S M, Brown C C

出版信息

J Pharmacol Exp Ther. 1986 Mar;236(3):627-33.

PMID:3512817
Abstract

Endogenous opioids (EOP) appear to inhibit the release of luteinizing hormone-releasing hormone and, subsequently, luteinizing hormone (LH). These observations have led to the hypothesis that EOP-containing neuronal systems may be involved in the onset of puberty. To examine this possibility, rats were challenged with naloxone and morphine, as probes to decrease or exaggerate, respectively, the effects of EOP on luteinizing hormone releasing hormone/LH release at intervals from birth to adulthood. Morphine had no effect on serum LH up to 15 days of age in males, but thereafter was maximally effective. On the other hand, the onset of adult-appropriate responses to morphine occurred much later in females (30-35 days) and the depressions in LH were consistently less pronounced than in comparably aged males. Naloxone produced large increases in LH in 10- and 25-day-old females, but was ineffective at 15 or 20 days. After day 25, the response to naloxone declined gradually, but was still significantly greater than control values in adults. In contrast, naloxone failed to increase serum LH from 10 to 30 days after birth in males. Beginning at 30 to 35 days of age, however, a sudden onset in the sensitivity to naloxone occurred which increased exponentially until 60 days. At this time, serum LH levels were 5 times greater in naloxone-treated males than in controls, and were twice those found in similarly treated females. These age- and sex-related differences in response to the opiates were not related to pharmacokinetic variables and also could not be attributed to gross maturational alternations in the hypothalamic-pituitary-gonadal axis.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

内源性阿片类物质(EOP)似乎会抑制促黄体生成激素释放激素的释放,进而抑制促黄体生成素(LH)的释放。这些观察结果引发了一种假说,即含有EOP的神经元系统可能参与青春期的启动。为了检验这种可能性,分别用纳洛酮和吗啡对大鼠进行刺激,作为降低或增强EOP对促黄体生成激素释放激素/LH释放影响的探针,刺激时间从出生到成年各阶段不等。在雄性大鼠中,直到15日龄吗啡对血清LH都没有影响,但此后效果最为显著。另一方面,雌性大鼠对吗啡产生成年期适当反应的起始时间要晚得多(30 - 35日龄),而且LH的降低程度始终不如同龄雄性大鼠明显。纳洛酮使10日龄和25日龄雌性大鼠的LH大幅升高,但在15日龄或20日龄时无效。25日龄后,对纳洛酮的反应逐渐下降,但在成年大鼠中仍显著高于对照值。相比之下,纳洛酮在雄性大鼠出生后10至30天未能增加血清LH。然而,从30至35日龄开始,对纳洛酮的敏感性突然出现,呈指数级增加直至60日龄。此时,纳洛酮处理的雄性大鼠血清LH水平是对照组的5倍,是同样处理的雌性大鼠的2倍。这些对阿片类药物反应的年龄和性别差异与药代动力学变量无关,也不能归因于下丘脑 - 垂体 - 性腺轴的总体成熟变化。(摘要截断于250字)

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