Bhanot R, Wilkinson M
Endocrinology. 1983 Aug;113(2):596-603. doi: 10.1210/endo-113-2-596.
We have examined (1) the effects of naloxone and an opiate peptide, FK 33-824, on LH and FSH secretion in immature male and female rats and (2) the influence of sexual maturation on the ability of this peptide to inhibit LH secretion. FK 33-824 potently inhibits LH secretion in the 48-h-gonadectomized rat. This effect could be blocked by coinjection of naloxone, suggesting that the peptide exerts its influence through opiate receptors. An endogenous opiate component in the control of LH secretion was demonstrated by examining the effect of naloxone injection alone. Naloxone rapidly stimulated LH secretion in the intact or the acutely gonadectomized rat. Naloxone or FK 33-824 did not modify LHRH-stimulated release of gonadotropins from organ cultures of anterior pituitary obtained from immature rats. This suggests, in agreement with other reports, that naloxone or FK 33-824 controls LH secretion via a central, possibly hypothalamic site. We further observed a clear age-related reduction in LH sensitivity to FK 33-824 in the acutely (48-h) gonadectomized rat. Dose-response studies indicated a 4-fold reduction in opiate responsiveness in the 10 days preceding the first ovulation. Thus, the doses required to reduce serum LH levels by 50% are 0.03, 0.04, 0.16, and 0.17 mg/kg, respectively, for the groups 12, 23, 29, and 33 days of age. In the male, a similar change was noted when responsiveness was compared in pre- and postpubertal rats; 50% inhibition was achieved at 0.25, 0.89, and 0.88 mg/kg FK 33-824 for rats aged 26, 70, and 90 days, respectively. The shift in sensitivity to FK 33-824 is probably not due to a change in clearance rates, but this cannot be completely ruled out. Thus, our demonstration of a maturation-related reduction in opiate inhibition of LH suggests a critical role for endogenous (hypothalamic?) opiate peptides and opiate receptors in the onset of sexual maturation. Our results may also provide a neurochemical basis for the well described shift in hypothalamic sensitivity to gonadal steroids that occurs with the approach of puberty.
我们研究了（1）纳洛酮和一种阿片肽FK 33 - 824对未成熟雄性和雌性大鼠促黄体生成素（LH）和促卵泡生成素（FSH）分泌的影响，以及（2）性成熟对该肽抑制LH分泌能力的影响。FK 33 - 824能有效抑制去性腺48小时大鼠的LH分泌。这种作用可被同时注射纳洛酮所阻断，这表明该肽是通过阿片受体发挥作用的。通过单独检测注射纳洛酮的效果，证实了在LH分泌调控中存在内源性阿片成分。纳洛酮能迅速刺激完整或急性去性腺大鼠的LH分泌。纳洛酮或FK 33 - 824不会改变从未成熟大鼠获得的垂体前叶器官培养物中促性腺激素释放激素（LHRH）刺激的促性腺激素释放。这与其他报道一致，表明纳洛酮或FK 33 - 824是通过中枢（可能是下丘脑）位点来控制LH分泌的。我们进一步观察到，在急性（48小时）去性腺大鼠中，LH对FK 33 - 824的敏感性随年龄增长明显降低。剂量反应研究表明，在首次排卵前10天，阿片反应性降低了4倍。因此，对于12、23、29和33日龄的组，使血清LH水平降低50%所需的剂量分别为0.03、0.04、0.16和0.17mg/kg。在雄性大鼠中，比较青春期前和青春期后的大鼠反应性时也观察到了类似变化；对于26、70和90日龄的大鼠，分别在0.25、0.89和0.88mg/kg的FK 33 - 824剂量下达到50%的抑制效果。对FK 33 - 824敏感性的变化可能不是由于清除率的改变，但也不能完全排除这种可能性。因此，我们证明了阿片对LH抑制作用与成熟相关的降低，这表明内源性（下丘脑？）阿片肽和阿片受体在性成熟开始过程中起关键作用。我们的结果也可能为青春期临近时下丘脑对性腺类固醇敏感性的显著变化提供神经化学基础。
