Centre for Neuroendocrinology and Department of Anatomy and Structural Biology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
Endocrinology. 2011 May;152(5):1979-88. doi: 10.1210/en.2010-1220. Epub 2011 Mar 1.
Pregnancy and lactation cause long-lasting enhancements in maternal behavior and other physiological functions, along with increased hypothalamic prolactin receptor expression. To directly test whether reproductive experience increases prolactin responsiveness in the arcuate, paraventricular, and supraoptic nuclei and the medial preoptic area, female rats experienced a full pregnancy and lactation or remained as age-matched virgin controls. At 5 wk after weaning, rats received 2.5, 100, or 4000 ng ovine prolactin or vehicle intracerebroventricularly. The brains underwent immunohistochemistry for the phosphorylated forms of signal transducer and activator of transcription 5 (pSTAT5) or ERK1/2 (pERK1/2). There was a marked increase in pSTAT5 and pERK1/2 in response to prolactin in the regions examined in both virgin and primiparous rats. Primiparous rats exhibited approximately double the number of prolactin-induced pSTAT5-immunoreactive cells as virgins, this effect being most apparent at the higher prolactin doses in the medial preoptic area and paraventricular and supraoptic nuclei and at the lowest prolactin dose in the arcuate nucleus. Dual-label immunohistochemistry showed that arcuate kisspeptin (but not oxytocin or dopamine) neurons displayed increased sensitivity to prolactin in reproductively experienced animals; these neurons may contribute to the reduction in prolactin concentration observed after reproductive experience. There was no effect of reproductive experience on prolactin-induced pERK1/2, indicating a selective effect on the STAT5 pathway. These data show that STAT5 responsiveness to prolactin is enhanced by reproductive experience in multiple hypothalamic regions. The findings may have significant implications for understanding postpartum disorders affecting maternal care and other prolactin-associated pathologies.
妊娠和哺乳会导致母体行为和其他生理功能的持久增强，同时增加下丘脑催乳素受体的表达。为了直接测试生殖经验是否会增加弓状核、室旁核和视上核以及内侧视前区的催乳素反应性，雌性大鼠经历了完整的妊娠和哺乳，或保持与年龄匹配的未交配对照组。在断奶后 5 周，大鼠接受 2.5、100 或 4000ng 羊催乳素或载体脑室给药。大脑接受磷酸化信号转导和转录激活因子 5（pSTAT5）或 ERK1/2（pERK1/2）的免疫组织化学染色。在未交配和初产大鼠的所有检查区域，催乳素都显著增加了 pSTAT5 和 pERK1/2。初产大鼠表现出催乳素诱导的 pSTAT5 免疫反应性细胞数量大约是未交配大鼠的两倍，这种效应在中脑前内侧区、室旁核和视上核的较高催乳素剂量和弓状核的最低催乳素剂量中最为明显。双标免疫组织化学显示，弓状核 kisspeptin（但不是催产素或多巴胺）神经元在生殖经验丰富的动物中对催乳素的敏感性增加；这些神经元可能有助于解释生殖经验后催乳素浓度的降低。生殖经验对催乳素诱导的 pERK1/2 没有影响，表明对 STAT5 途径有选择性影响。这些数据表明，催乳素对 STAT5 的反应性在多个下丘脑区域会因生殖经验而增强。这些发现可能对理解影响母婴护理和其他与催乳素相关的病理的产后障碍具有重要意义。
