Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
J Neuroendocrinol. 2018 Sep;30(9):e12613. doi: 10.1111/jne.12613. Epub 2018 Aug 7.
Prolactin (PRL) is a peptide hormone that performs over 300 biological functions, including those that require binding to prolactin receptor (PRL-R) in neurones within the central nervous system (CNS). To enter the CNS, circulating PRL must overcome the blood-brain barrier. Accordingly, areas of the brain that do not possess a blood-brain barrier, such as the subfornical organ (SFO), are optimally positioned to interact with systemic PRL. The SFO has been classically implicated in energy and fluid homeostasis but has the potential to influence oestrous cyclicity and gonadotrophin release, which are also functions of PRL. We aimed to confirm and characterise the expression of PRL-R in the SFO, as well as identify the effects of PRL application on membrane excitability of dissociated SFO neurones. Using a quantitative real-time polymerase chain reaction, we found that PRL-R mRNA in the SFO of male and female Sprague Dawley rats did not significantly differ between juvenile and sexually mature rats (P = .34), male and female rats (P = .97) or across the oestrous cycle (P = .54). Patch-clamp recordings were obtained in juvenile male rats to further investigate the actions of PRL at the SFO. Dissociated SFO neurones perfused with 1 μmol L PRL resulted in 2 responsive subpopulations of neurones; 40% depolarised (n = 15/43, 11.3 ± 1.7 mV) and 14% hyperpolarised (n = 6/43, -6.7 ± 1.4 mV) to PRL application. Within the range of 10 pmol L to 1 μmol L , the concentrations of PRL were not significantly different in either the magnitude (P = .53) or proportion (P = .19) of response. Furthermore, PRL application significantly reduced the transient K current in 67% of SFO neurones in voltage-clamp configuration (n = 6/9, P = .02). The stability in response to PRL and expression of PRL-R in the SFO suggests that PRL function is conserved across physiological states and circulating PRL concentrations, prompting further investigations aiming to clarify the nature of PRL function in the SFO.
催乳素 (PRL) 是一种肽激素，具有 300 多种生物学功能，包括在中枢神经系统 (CNS) 内神经元中与催乳素受体 (PRL-R) 结合的功能。为了进入 CNS，循环中的 PRL 必须克服血脑屏障。因此，没有血脑屏障的大脑区域，如穹窿下器官 (SFO)，最适合与全身 PRL 相互作用。SFO 经典上被认为与能量和液体稳态有关，但也有可能影响发情周期和促性腺激素释放，这也是 PRL 的功能。我们旨在确认和描述 PRL-R 在 SFO 中的表达，并确定 PRL 应用对分离的 SFO 神经元膜兴奋性的影响。使用定量实时聚合酶链反应，我们发现雄性和雌性 Sprague Dawley 大鼠 SFO 中的 PRL-R mRNA 在幼年和性成熟大鼠之间（P =.34）、雄性和雌性大鼠之间（P =.97）或发情周期之间没有显著差异（P =.54）。在幼年雄性大鼠中进行膜片钳记录，以进一步研究 PRL 在 SFO 中的作用。用 1 μmol/L PRL 灌流分离的 SFO 神经元导致 2 个反应性神经元亚群；40%去极化（n = 15/43，11.3 ± 1.7 mV）和 14%超极化（n = 6/43，-6.7 ± 1.4 mV）对 PRL 应用。在 10 pmol/L 至 1 μmol/L 的范围内，PRL 的浓度在幅度（P =.53）或比例（P =.19）方面均无显著差异。此外，PRL 应用显著降低了电压钳构型中 67%的 SFO 神经元中的瞬态 K 电流（n = 6/9，P =.02）。SFO 中对 PRL 的反应稳定性和 PRL-R 的表达表明，PRL 功能在生理状态和循环 PRL 浓度下是保守的，这促使进一步的研究旨在阐明 PRL 在 SFO 中的功能性质。
