Dopamine agonists both stimulate and inhibit prolactin release in GH4ZR7 cells
Dopamine agonists both stimulate and inhibit prolactin release in GH4ZR7 cells
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DOI：
10.1530/eje.0.1410387
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发表时间：
1999-10-01
影响因子：
5.8
通讯作者：
Shin, SH
中科院分区：
文献类型：
--
作者：
Chang, A;Shin, SH
垂体前叶的催乳素分泌受多种因素调节，包括催乳素释放抑制因子（PIFs）和催乳素释放因子。然而，PIF通常在生物系统中占主导地位，发挥紧张性抑制作用，并且生理PII被认为是多巴胺。然而，越来越多的证据表明，多巴胺不仅可以抑制，而且可以刺激催乳素的释放。许多研究者认为，这是通过激活多巴胺受体的抑制和刺激亚型来实现的。我们试图用GH（4）ZR（7）细胞证明多巴胺受体的一种亚型既能抑制又能刺激催乳素的释放。GH（4）ZR（7）细胞只表达短形式的多巴胺D-2受体（D-2s）。D-2受体激动剂（多巴胺、阿扑吗啡和溴隐亭）在低浓度时刺激GH（4）ZR（7）细胞分泌催乳素，高浓度时则抑制其分泌，D-2受体拮抗剂氟哌啶醇可阻断其抑制作用，而Ras不能阻断多巴胺的刺激作用。预先处理细胞与酚苄明，受体烷化剂，取消多巴胺诱导的刺激和抑制作用。我们的研究结果支持了多巴胺刺激催乳素释放是通过多巴胺D-2s受体介导的这一论点，因为GH（4）Z（7）细胞在多巴胺受体中只有D-2s受体。我们的结论是，D-2s受体能够刺激和抑制催乳素的释放，可能是通过低浓度的多巴胺能药物激活G（s）蛋白和高浓度的多巴胺能药物激活G（i）蛋白。
Prolactin secretion from the anterior pituitary gland is regulated by multiple factors including prolactin-release inhibiting factors (PIFs) and prolactin releasing factors. PIFs, however, usually dominate to exert a tonic inhibition in the biological system, and the physiological PII: is believed to be dopamine. However there is accumulating evidence that dopamine can not only inhibit but also stimulate prolactin release. Many investigators believe that this is achieved by activating inhibitory and stimulatory subtypes of dopamine receptors. We tried to demonstrate that one subtype of dopamine receptors is capable of both inhibiting or stimulating prolactin release using GH(4)ZR(7) cells, GH(4)ZR(7) cells express only a short form of dopamine D-2 receptors (D-2s). Low concentrations of three well-established D-2 receptor agonists (dopamine, apomorphine and bromocriptine) stimulated prolactin release from GH(4)ZR(7) cells while high concentrations inhibited the release, Haloperidol, a D-2 receptor antagonist, blocked the inhibitory action, but Ras unable to block the dopamine-induced stimulatory action. Pretreatment of cells with phenoxybenzamine, a receptor alkylating agent, abolished both the dopamine-induced stimulatory and inhibitory actions. Our results support the thesis that the stimulation of prolactin release induced by dopamine is mediated through dopamine D-2s receptors since the GH(4)Z(7) cells have only D-2s receptors among dopamine receptors. We have concluded that the D-2s receptor is capable of both stimulating and inhibiting prolactin release, probably via the activation of a G(s) protein by low concentrations and a G(i) protein by high concentrations of dopaminergic agents.