Blank M S, Fabbri A, Catt K J, Dufau M L
Endocrinology. 1986 May;118(5):2097-101. doi: 10.1210/endo-118-5-2097.
Morphine sulfate was found to have a direct inhibitory effect on both basal and GnRH-stimulated LH release by cultured rat pituitary cells. The inhibitory effect of morphine on LH release was prevented by the opiate antagonist naltrexone, and treatment of cells with naltrexone or beta-endorphin antiserum significantly increased basal LH release. Also, incubation of pituitary cells with CRF caused a significant decrease in basal LH release, an effect that was reversed by naltrexone. Saturable opiate-binding sites were demonstrated in enriched gonadotrophs by [3H]etorphine binding studies. The ability of morphine to inhibit gonadotropin secretion through a direct action on pituitary opiate receptors suggests that long term exposure to exogenous opiates may suppress reproductive function at the hypophyseal level. In addition, the converse effects of CRF and naltrexone or beta-endorphin antiserum on LH release indicate that intrapituitary opioid peptides could exert a paracrine inhibitory action on the gonadotroph.
研究发现，硫酸吗啡对培养的大鼠垂体细胞的基础促黄体生成素（LH）释放以及促性腺激素释放激素（GnRH）刺激的LH释放均有直接抑制作用。阿片拮抗剂纳曲酮可阻止吗啡对LH释放的抑制作用，用纳曲酮或β-内啡肽抗血清处理细胞可显著增加基础LH释放。此外，垂体细胞与促肾上腺皮质激素释放因子（CRF）孵育会导致基础LH释放显著减少，而纳曲酮可逆转这一效应。通过[3H]埃托啡结合研究在富集的促性腺激素细胞中证实了可饱和的阿片结合位点。吗啡通过直接作用于垂体阿片受体抑制促性腺激素分泌的能力表明，长期暴露于外源性阿片类药物可能在垂体水平抑制生殖功能。此外，CRF与纳曲酮或β-内啡肽抗血清对LH释放的相反作用表明，垂体内阿片肽可能对促性腺激素细胞发挥旁分泌抑制作用。
