Animal Physiology Research Unit, School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
J Neuroendocrinol. 1992 Apr;4(2):167-72. doi: 10.1111/j.1365-2826.1992.tb00155.x.
A nocturnal surge of prolactin (PRL) occurs in the dark period preceding parturition in the rat. The roles of oxytocin, vasoactive intestinal peptide (VIP), serotonin and the opioids in controlling the antepartum PRL surge were investigated by examining PRL secretion over the last 2 days of pregnancy in the presence of antagonists to these neurohormonal factors. Serial blood samples were collected from unanesthetized, freely moving rats via indwelling jugular cannulae, and plasma PRL was measured by radioimmunoassay. In control rats PRL levels rose in a nocturnal surge peaking at 223 ± 34 ng/ml (n = 6) at 0500 h on day 21 of pregnancy, the day of parturition. Intra-arterial infusion of the oxytocin antagonist desGly-NH(2) d(CH(2) )(5) [Tyr(Me)(2) , Thr(4) ]-OVT at a dose sufficient to completely block milk ejection (10 μg/h) had no effect on this PRL surge. Infusion of the VIP antagonist [4Cl-D-Phe(6) ,Leu(17) ]-VIP at 2 μg/h from 2200 h on day 20 until 0500 h on day 21 significantly attenuated the antepartum PRL surge, reducing the peak to 76 ± 28 ng/ml at 0500 h on day 21 (n = 6; P<0.001). Naloxone, the opiate receptor antagonist, inhibited the antepartum PRL surge in a dose-dependent manner. Infused at 2 mg/h naloxone partially reduced the magnitude of the PRL surge, which peaked at 128 ± 24 ng/ml at 0300 h on day 21 (n = 4; P<0.05), while at 10 mg/h naloxone totally abolished the PRL surge (n = 6; P<0.001). Injection of the serotonin synthesis inhibitor ρ-chlorophenylalanine (250 mg/kg, sc at 1700 h on days 19 and 20 of pregnancy) increased the magnitude of the antepartum PRL surge to a peak of 327 ± 48 ng/ml at 0500 h on day 21 (n = 5), compared with 244 ± 24 ng/ml at the same time in vehicle-injected controls (P<0.05; n = 5). The results demonstrate that the antepartum PRL surge is stimulated by an opioid mechanism, and also by VIP. Oxytocin and serotonin have no role in stimulating PRL secretion during late pregnancy.
在大鼠分娩前的黑暗期，催乳素（PRL）会在夜间出现激增。通过检查这些神经激素因子存在时的最后 2 天妊娠期间 PRL 的分泌，研究了催产素、血管活性肠肽（VIP）、血清素和阿片类药物在控制产前 PRL 激增中的作用。通过留置颈内套管从未麻醉的自由活动大鼠中采集连续的血液样本，并通过放射免疫测定法测量血浆 PRL。在对照大鼠中，PRL 水平在夜间激增，在妊娠第 21 天的 0500 时达到高峰，为 223 ± 34ng/ml（n = 6），即分娩当天。以足以完全阻断乳汁排出的剂量（10μg/h）输注催产素拮抗剂 desGly-NH(2) d(CH(2) )(5)[Tyr(Me)(2), Thr(4) ]-OVT 对这种 PRL 激增没有影响。从妊娠第 20 天的 2200 时开始，以 2μg/h 的剂量输注 VIP 拮抗剂[4Cl-D-Phe(6),Leu(17) ]-VIP，直至妊娠第 21 天的 0500 时，显著减弱了产前 PRL 激增，使第 21 天的 0500 时的峰值降低至 76 ± 28ng/ml（n = 6；P<0.001）。阿片受体拮抗剂纳洛酮以剂量依赖性方式抑制产前 PRL 激增。以 2mg/h 的剂量输注纳洛酮部分减少了 PRL 激增的幅度，在第 21 天的 0300 时达到峰值，为 128 ± 24ng/ml（n = 4；P<0.05），而 10mg/h 的纳洛酮完全消除了 PRL 激增（n = 6；P<0.001）。在妊娠第 19 天和第 20 天的 1700 时，以 250mg/kg 的剂量 sc 注射 5-羟色氨酸合成抑制剂 ρ-氯苯丙氨酸（ρ-chlorophenylalanine），将产前 PRL 激增的幅度增加到第 21 天的 0500 时的峰值 327 ± 48ng/ml（n = 5），而在相同时间，在载体注射对照中为 244 ± 24ng/ml（n = 5；P<0.05）。结果表明，产前 PRL 激增是由阿片类机制刺激的，也是由 VIP 刺激的。催产素和 5-羟色胺在妊娠晚期刺激 PRL 分泌中没有作用。
