Oxytocin Neurons Enable Melanocortin Regulation of Male Sexual Function in Mice

  • Erin Semple
  • Firas Shalabi
  • Jennifer W. Hill


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 (tbMC4RSim1 mice) or on a subset of Sim1 neurons, namely oxytocin neurons (tbMC4Roxt 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 tbMC4RSim1 and tbMC4Roxt 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.


Paraventricular nucleus Erectile dysfunction Ejaculation Melanocortin Obesity PVH Hypothalamus Oxytocin Male Mice Sim1 Sim-1 MC4R POMC 



We would like to acknowledge the University of Toledo Advanced Microscopy & Imaging Center and the University of Virginia Ligand Assay and Analysis Core for the analysis of LH/FSH serum concentrations.

Funding Information

This work was supported by NIH award R01 HD081792 to JWH. The University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core is supported by the Eunice Kennedy Shriver NICHD/NIH (NCTRI) Grant P50-HD28934.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Research Involving Human Participants and/or Animals

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Erin Semple
    • 1
  • Firas Shalabi
    • 1
  • Jennifer W. Hill
    • 1
  1. 1.Department of Physiology and PharmacologyUniversity of Toledo College of Medicine and Life SciencesToledoUSA

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