Estrogen inhibits D2S receptor-regulated Gi3 and Gs protein interactions to stimulate prolactin production and cell proliferation in lactotropic cells.
Estrogen inhibits D2S receptor-regulated Gi3 and Gs protein interactions to stimulate prolactin production and cell proliferation in lactotropic cells.
复制标题
DOI：
10.1530/joe-12-0125
复制
发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
Anirvan M. Sengupta;D. Sarkar
中科院分区：
文献类型：
--
作者：
Anirvan M. Sengupta;D. Sarkar
已知神经递质多巴胺（DA）可抑制垂体中催乳素（PRL）的分泌和乳变性物的增殖。在雌二醇（E(2)）诱导的PRL产生和细胞增殖过程中，多巴胺-2 （D2）受体短（D2S）异构体的表达水平降低，而D2受体长（D2L）异构体的表达水平升高。为了评估这些D2受体同种异构体在E(2)调节的嗜乳细胞功能中的作用，我们比较了E(2)对富含乳变性物和乳变性物衍生的PR1细胞中仅含D2S异构体（D2S细胞）、D2L同种异构体（D2L细胞）或不含D2受体（V细胞）的PR1水平、细胞增殖和G蛋白的影响。此外，我们还确定了G蛋白阻断对E(2)诱导的PRL产生和细胞增殖的影响。我们在这里发现，E(2)对G蛋白的作用、PRL的产生和细胞增殖在D2S细胞中最大程度地实现，在D2L细胞中相反或只有少量实现，而在V细胞中则不存在。我们还发现，与D2L或V细胞相比，DA和百日咳毒素调节E(2)对PRL、G蛋白和细胞增殖的作用在D2S细胞中得到最大程度的实现。此外，我们提供的证据表明，在D2S受体的控制下，Gi3对Gs的抑制作用受到E的抑制(2)。这些结果提示，抑制d2s调控的Gi3对Gs蛋白的抑制可能是控制E(2)激活的PRL合成和细胞增殖的机制之一。
The neurotransmitter dopamine (DA) is known to inhibit prolactin (PRL) secretion and the proliferation of lactotropes in the pituitary gland. Dopamine-2 (D2) receptor short (D2S) isoform is expressed in a reduced level while the D2 receptor long (D2L) isoform is expressed in an elevated level during estradiol (E(2))-induced PRL production and cell proliferation in lactotropes. To evaluate the role of these D2 receptor isoforms in E(2)-regulated lactotropic cell function, we compared E(2) effects on the level of PRL, cell proliferation, and G proteins in enriched lactotropes and lactotrope-derived PR1 cells containing only D2S isoform (D2S cells), D2L isoform (D2L cells), or no D2 receptor (V cells). Additionally, we determined the effects of G protein blockade on the E(2)-induced PRL production and cell proliferation in these cells. We here show that E(2) actions on G proteins, PRL production, and cell proliferation were maximally achieved in D2S cells, oppositely or marginally achieved in D2L cells, and absent in V cells. We also show that the DA and pertussis toxin modulations of E(2) actions on PRL, G proteins, and cell proliferation were maximally achieved in D2S cells compared with in D2L or V cells. Furthermore, we provide evidence for the existence of an inhibitory action of Gi3 on Gs that is under the control of the D2S receptor and is inhibited by E(2). These results suggest that the suppression of D2S-regulated Gi3 inhibition of Gs protein may be one of the mechanisms controlling E(2)-activated PRL synthesis and cell proliferation in lactotropes.