Widmer Hélène, Ludwig Mike, Bancel Frédéric, Leng Gareth, Dayanithi Govindan
School of Biomedical and Clinical Laboratory Sciences, University of Edinburgh College of Medical and Veterinary Sciences, Edinburgh, UK.
J Physiol. 2003 Apr 1;548(Pt 1):233-44. doi: 10.1113/jphysiol.2002.036863. Epub 2003 Feb 14.
In adult rats somato-dendritic release of oxytocin and vasopressin from magnocellular neurones in the supraoptic nucleus of the hypothalamus has important autoregulatory actions on the neuronal electrical activity, and in neonatal rats it plays a role in the development of dendritic arborisation. In the adult, oxytocin effects are modulated by allopregnanolone via an interaction with inhibitory GABAA receptors. This study examined the effects of allopregnanolone, progesterone and 17beta-oestradiol on oxytocin and vasopressin release from intact isolated supraoptic nuclei and from the neurophypophyses in rats of differing ages. In supraoptic nuclei from rats of 3-4 weeks old or less, all three neurosteroids induced oxytocin release from the isolated supraoptic nucleus, but only allopregnanolone induced significant release of vasopressin. Surprisingly, in these very young rats, allopregnanolone-induced oxytocin release was inhibited by GABAA receptor antagonists as well as by an oxytocin receptor antagonist. By contrast, in supraoptic nuclei from adult rats allopregnanolone-induced oxytocin release was much smaller, and was enhanced in the presence of bicuculline. The GABAA receptor agonist muscimol also induced oxytocin release from supraoptic nuclei in young rats, but had no effect in adult rats. Oxytocin cells isolated from young rats showed an increase in [Ca2+]i in response to both allopregnanolone and muscimol. Allopregnanolone had no effect on [Ca2+]i or on the release of oxytocin or vasopressin from neurohypophysial axon terminals in either young or old rats. We conclude that, in very young rats, (i) neurosteroids induce oxytocin release from the supraoptic nucleus by a mechanism that partly depends on the presence of GABA, which in young rats is depolarising to oxytocin cells, and which also partly depends upon endogenous oxytocin, and (ii) the effect of allopregnanolone upon oxytocin release changes with age, as the functional activity of GABAA receptors changes from excitation to inhibition of oxytocin cells.
在成年大鼠中，下丘脑视上核大细胞神经元的催产素和血管加压素的体树突释放对神经元电活动具有重要的自调节作用，而在新生大鼠中，它在树突分支的发育中起作用。在成年期，孕烷醇酮通过与抑制性GABAA受体相互作用来调节催产素的作用。本研究检测了孕烷醇酮、孕酮和17β-雌二醇对不同年龄大鼠完整分离的视上核以及神经垂体中催产素和血管加压素释放的影响。在3至4周龄及以下大鼠的视上核中，所有三种神经甾体均诱导分离的视上核释放催产素，但只有孕烷醇酮诱导血管加压素显著释放。令人惊讶的是，在这些非常年幼的大鼠中，孕烷醇酮诱导的催产素释放受到GABAA受体拮抗剂以及催产素受体拮抗剂的抑制。相比之下，在成年大鼠的视上核中，孕烷醇酮诱导的催产素释放要小得多，并且在荷包牡丹碱存在的情况下会增强。GABAA受体激动剂蝇蕈醇也诱导年幼大鼠视上核释放催产素，但对成年大鼠没有影响。从年幼大鼠分离的催产素细胞对孕烷醇酮和蝇蕈醇均显示[Ca2+]i增加。孕烷醇酮对年幼或成年大鼠神经垂体轴突终末的[Ca2+]i或催产素及血管加压素的释放均无影响。我们得出结论，在非常年幼的大鼠中，(i)神经甾体通过一种部分依赖于GABA存在的机制诱导视上核释放催产素，在年幼大鼠中GABA使催产素细胞去极化，并且还部分依赖于内源性催产素，以及(ii)随着年龄增长，孕烷醇酮对催产素释放的影响发生变化，因为GABAA受体的功能活性从对催产素细胞的兴奋转变为抑制。
