Zuure W A, Quennell J H, Anderson G M
Centre for Neuroendocrinology and Department of Anatomy, University of Otago School of Medical Sciences, Dunedin, New Zealand.
J Neuroendocrinol. 2016 Mar;28(3):12357. doi: 10.1111/jne.12357.
The adipocyte-derived hormone leptin plays a critical role in the control of reproduction via signalling in hypothalamic neurones. The drivers of the hypothalamic-pituitary-gonadal axis, the gonadotrophin-releasing hormone (GnRH) neurones, do not have the receptors for leptin. Therefore, intermediate leptin responsive neurones must provide leptin-to-GnRH signalling. We investigated the populations of leptin responsive neurones that provide input to the rostral preoptic area (rPOA) where GnRH cell bodies reside. Fluorescent retrograde tracer beads (RetroBeads; Lumafluor Inc., Naples, FL, USA) were injected into the rPOA of transgenic leptin receptor enhanced green fluorescent protein (Lepr-eGFP) reporter mice. Uptake of the RetroBeads by Lepr-eGFP neurones was assessed throughout the hypothalamus. RetroBead uptake was most evident in the medial arcuate nucleus (ARC), the dorsomedial nucleus (DMN) and the ventral premammillary nucleus (PMV) of the hypothalamus. The uptake of RetroBeads specifically by Lepr-eGFP neurones was highest in the medial ARC (18% of tracer-labelled neurones Lepr-eGFP-positive). Because neurones that are both leptin responsive and GABAergic play a critical role in the regulation of fertility by leptin, we next focussed on the location of these populations. To address whether GABAergic neurones in leptin-responsive hypothalamic regions project to the rPOA, the experiment was repeated in GABA neurone reporter mice (Vgat-tdTomato). Between 10% and 45% of RetroBead-labelled neurones in the ARC were GABAergic, whereas uptake of tracer by GABAergic neurones in the DMN and PMV was very low (< 5%). These results show that both leptin responsive and GABAergic neurones from the ARC project to the region of the GnRH cell bodies. Our findings suggest that LEPR-expressing GABA neurones from the ARC may be mediators of leptin-to-GnRH signalling.
脂肪细胞衍生的激素瘦素通过在下丘脑神经元中发出信号，在生殖控制中发挥关键作用。下丘脑 - 垂体 - 性腺轴的驱动者，即促性腺激素释放激素（GnRH）神经元，没有瘦素受体。因此，中间的瘦素反应性神经元必须提供从瘦素到GnRH的信号传导。我们研究了向GnRH细胞体所在的视前区前部（rPOA）提供输入的瘦素反应性神经元群体。将荧光逆行示踪珠（RetroBeads；Lumafluor公司，美国佛罗里达州那不勒斯）注射到转基因瘦素受体增强型绿色荧光蛋白（Lepr-eGFP）报告基因小鼠的rPOA中。评估整个下丘脑内Lepr-eGFP神经元对RetroBeads的摄取情况。RetroBeads摄取在下丘脑的内侧弓状核（ARC）、背内侧核（DMN）和腹侧乳头前核（PMV）中最为明显。RetroBeads特异性地被Lepr-eGFP神经元摄取的情况在内侧ARC中最高（示踪剂标记神经元的18%为Lepr-eGFP阳性）。由于既对瘦素产生反应又具有γ-氨基丁酸（GABA）能的神经元在瘦素对生育能力的调节中起关键作用，我们接下来关注这些群体的位置。为了确定瘦素反应性下丘脑区域的GABA能神经元是否投射到rPOA，我们在GABA神经元报告基因小鼠（Vgat-tdTomato）中重复了该实验。ARC中10%至45%的RetroBead标记神经元是GABA能的，而DMN和PMV中GABA能神经元对示踪剂的摄取非常低（<5%）。这些结果表明，来自ARC的瘦素反应性和GABA能神经元都投射到GnRH细胞体所在区域。我们的研究结果表明，来自ARC的表达LEPR的GABA能神经元可能是瘦素到GnRH信号传导的介质。
