Department of Biological Science, Florida State University, BRF 206, Tallahassee, Florida 32306, USA.
Endocrinology. 2010 Apr;151(4):1806-13. doi: 10.1210/en.2009-1267. Epub 2010 Feb 22.
Although removal of dopamine inhibition is established as a major factor in prolactin (PRL) release, a large body of evidence suggests that hypothalamic oxytocin (OT) may serve as a PRL-releasing hormone in the rat. PRL release is modulated by estradiol (E2), which rises between diestrus and proestrus of the estrous cycle, causing a PRL surge in the afternoon of proestrus. Given that E2 strongly modulates OT actions in both central and peripheral tissues, OT action on lactotrophs might also be modulated by the stage of the estrous cycle. To test this hypothesis, we have monitored PRL release and intracellular calcium levels (Ca(2+)) induced by OT in pituitary lactotrophs obtained from female rats in either diestrus 1 or proestrus. We found that both secretory and Ca(2+) responses to OT are significantly increased in lactotrophs obtained on proestrus. Moreover, we show that these differences are due to an increase in both the number of OT-responding lactotrophs and the magnitude of their individual Ca(2+) responses. Both secretory and Ca(2+) responses were abolished by a specific OT antagonist. Finally, dose-dependent studies show that the increased PRL-releasing effect of OT on proestrus is significant over a wide range of concentrations, particularly those observed in hypophyseal portal plasma. These results suggest that the rising E2 titers that culminate on proestrus facilitate the stimulatory action of OT on lactotrophs and support the notion that OT is a PRL-releasing hormone with an important role in the production of the proestrous surge of PRL.
尽管去除多巴胺抑制被认为是催乳素（PRL）释放的主要因素，但大量证据表明，下丘脑催产素（OT）可能是大鼠的 PRL 释放激素。PRL 的释放受雌二醇（E2）的调节，E2 在发情周期的间情期和发情前期之间升高，导致发情前期下午出现 PRL 激增。鉴于 E2 强烈调节 OT 在中枢和外周组织中的作用，OT 对泌乳细胞的作用也可能受到发情周期阶段的调节。为了验证这一假设，我们监测了发情前期和间情期的雌性大鼠垂体泌乳细胞中 OT 诱导的 PRL 释放和细胞内钙离子浓度(Ca(2+))。我们发现，OT 诱导的分泌和Ca(2+)反应在发情前期的泌乳细胞中均显著增加。此外，我们表明这些差异是由于 OT 反应性泌乳细胞的数量增加以及它们个体Ca(2+)反应的幅度增加所致。OT 的特异性拮抗剂可消除分泌和Ca(2+)反应。最后，剂量依赖性研究表明，OT 在发情前期对 PRL 的释放作用在广泛的浓度范围内显著增加，特别是在垂体门脉血浆中观察到的浓度范围内。这些结果表明，发情前期达到高峰的 E2 浓度升高促进了 OT 对泌乳细胞的刺激作用，并支持 OT 是一种具有重要作用的 PRL 释放激素的观点，在发情前期 PRL 激增的产生中发挥重要作用。
