Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, 3000 Arlington Ave., Toledo, OH, 43614, USA.
Mol Neurobiol. 2019 Sep;56(9):6310-6323. doi: 10.1007/s12035-019-1514-5. Epub 2019 Feb 12.
The melanocortin pathway has been implicated in both metabolism and sexual function. When the melanocortin 4 receptor (MC4R) is knocked out globally, male mice display obesity, low sexual desire, and copulatory difficulties; however, it is unclear whether these phenotypes are interdependent. To elucidate the neuronal circuitry involved in sexual dysfunction in MC4R knockouts, we re-expressed the MC4R in these mice exclusively on Sim1 neurons (tbMC4R mice) or on a subset of Sim1 neurons, namely oxytocin neurons (tbMC4R mice). The groups were matched at young ages to control for the effects of obesity. Interestingly, young MC4R null mice had no deficits in sexual motivation or erectile function. However, MC4R null mice were found to have an increased latency to reach ejaculation compared to control mice, which was restored in both tbMC4R and tbMC4R mice. These results indicate that melanocortin signaling via the MC4R on oxytocin neurons is important for normal ejaculation independent of the male's metabolic health.
黑素皮质素途径与代谢和性功能都有关联。当黑素皮质素 4 受体 (MC4R) 被整体敲除时，雄性小鼠会表现出肥胖、性欲低下和交配困难；然而，这些表型是否相互依赖尚不清楚。为了阐明 MC4R 敲除小鼠性功能障碍涉及的神经元回路，我们在这些小鼠中仅在 Sim1 神经元（tbMC4R 小鼠）或 Sim1 神经元的一个子集，即催产素神经元（tbMC4R 小鼠）上重新表达 MC4R。这些组在年轻时进行匹配，以控制肥胖的影响。有趣的是，年轻的 MC4R 缺失小鼠在性动机或勃起功能方面没有缺陷。然而，与对照组相比，MC4R 缺失小鼠达到射精的潜伏期延长，而这在 tbMC4R 和 tbMC4R 小鼠中都得到了恢复。这些结果表明，通过 oxytocin 神经元上的 MC4R 传递的黑素皮质素信号对于正常射精是重要的，而与雄性的代谢健康无关。
