Augustine Rachael A, Ladyman Sharon R, Bouwer Gregory T, Alyousif Yousif, Sapsford Tony J, Scott Victoria, Kokay Ilona C, Grattan David R, Brown Colin H
Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
Centre for Neuroendocrinology, University of Otago, Dunedin, New Zealand.
J Physiol. 2017 Jun 1;595(11):3591-3605. doi: 10.1113/JP273712. Epub 2017 Mar 23.
During lactation, prolactin promotes milk synthesis and oxytocin stimulates milk ejection. In virgin rats, prolactin inhibits the activity of oxytocin-secreting neurones. We found that prolactin inhibition of oxytocin neurone activity is lost in lactation, and that some oxytocin neurones were excited by prolactin in lactating rats. The change in prolactin regulation of oxytocin neurone activity was not associated with a change in activation of intracellular signalling pathways known to couple to prolactin receptors. The change in prolactin regulation of oxytocin neurone activity in lactation might allow coordinated activation of both populations of neurones when required for successful lactation.
Secretion of prolactin for milk synthesis and oxytocin for milk secretion is required for successful lactation. In virgin rats, prolactin inhibits oxytocin neurones but this effect would be counterproductive during lactation when secretion of both hormones is required for synthesis and delivery of milk to the newborn. Hence, we determined the effects of intracerebroventricular (i.c.v.) prolactin on oxytocin neurones in urethane-anaesthetised virgin, pregnant and lactating rats. Prolactin (2 μg) consistently inhibited oxytocin neurones in virgin and pregnant rats (by 1.9 ± 0.4 and 1.8 ± 0.5 spikes s , respectively), but not in lactating rats; indeed, prolactin excited six of 27 oxytocin neurones by >1 spike s in lactating rats but excited none in virgin or pregnant rats (χ = 7.2, P = 0.03). Vasopressin neurones were unaffected by prolactin (2 μg) in virgin rats but were inhibited by 1.1 ± 0.2 spikes s in lactating rats. Immunohistochemistry showed that i.c.v. prolactin increased oxytocin expression in virgin and lactating rats and increased signal transducer and activator of transcription 5 phosphorylation to a similar extent in oxytocin neurones of virgin and lactating rats. Western blotting showed that i.c.v. prolactin did not affect phosphorylation of extracellular regulated kinase 1 or 2, or of Akt in the supraoptic or paraventricular nuclei of virgin or lactating rats. Hence, prolactin inhibition of oxytocin neurones is lost in lactation, which might allow concurrent elevation of prolactin secretion from the pituitary gland and activation of oxytocin neurones for synthesis and delivery of milk to the newborn.
在哺乳期，催乳素促进乳汁合成，催产素刺激乳汁排出。在未生育的大鼠中，催乳素抑制分泌催产素的神经元的活性。我们发现，在哺乳期催乳素对催产素神经元活性的抑制作用消失，并且在哺乳期大鼠中一些催产素神经元被催乳素兴奋。催乳素对催产素神经元活性调节的变化与已知与催乳素受体偶联的细胞内信号通路激活的变化无关。哺乳期催乳素对催产素神经元活性调节的变化可能使两种神经元群体在成功哺乳所需时能够协同激活。
成功哺乳需要分泌用于乳汁合成的催乳素和用于乳汁分泌的催产素。在未生育的大鼠中，催乳素抑制催产素神经元，但在哺乳期，当两种激素的分泌对于乳汁合成和向新生仔鼠输送乳汁都是必需的时候，这种作用会适得其反。因此，我们测定了脑室内（i.c.v.）注射催乳素对氨基甲酸乙酯麻醉的未生育、怀孕和哺乳期大鼠催产素神经元的影响。催乳素（2μg）持续抑制未生育和怀孕大鼠的催产素神经元（分别为1.9±0.4和1.8±0.5个峰/秒），但对哺乳期大鼠没有影响；实际上，催乳素使哺乳期大鼠27个催产素神经元中的6个兴奋，兴奋幅度大于1个峰/秒，但在未生育或怀孕大鼠中未兴奋任何一个催产素神经元（χ² = 7.2，P = 0.03）。在未生育大鼠中，加压素神经元不受催乳素（2μg）影响，但在哺乳期大鼠中被抑制，抑制幅度为1.1±0.2个峰/秒。免疫组织化学显示，脑室内注射催乳素增加未生育和哺乳期大鼠的催产素表达，并在未生育和哺乳期大鼠的催产素神经元中使信号转导和转录激活因子5磷酸化增加到相似程度。蛋白质印迹法显示，脑室内注射催乳素不影响未生育或哺乳期大鼠视上核或室旁核中细胞外调节激酶1或2或Akt的磷酸化。因此，在哺乳期催乳素对催产素神经元的抑制作用消失，这可能使垂体分泌的催乳素和催产素神经元的激活同时增加，以合成乳汁并输送给新生仔鼠。
