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Melanocortin 4 receptor signaling in Sim1 neurons permits sexual receptivity in female mice.
Semple, Erin A; Harberson, Mitchell T; Xu, Baijie; Rashleigh, Rebecca; Cartwright, Tori L; Braun, Jessica J; Custer, Amy C; Liu, Chen; Hill, Jennifer W.
Afiliação
  • Semple EA; Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH, United States.
  • Harberson MT; Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH, United States.
  • Xu B; Center for Hypothalamic Research, University of Texas Southwestern, Dallas, TX, United States.
  • Rashleigh R; Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH, United States.
  • Cartwright TL; Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH, United States.
  • Braun JJ; Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH, United States.
  • Custer AC; Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH, United States.
  • Liu C; Center for Hypothalamic Research, University of Texas Southwestern, Dallas, TX, United States.
  • Hill JW; Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH, United States.
Front Endocrinol (Lausanne) ; 14: 983670, 2023.
Article em En | MEDLINE | ID: mdl-37033219
ABSTRACT

Introduction:

Female sexual dysfunction affects approximately 40% of women in the United States, yet few therapeutic options exist for these patients. The melanocortin system is a new treatment target for hypoactive sexual desire disorder (HSDD), but the neuronal pathways involved are unclear.

Methods:

In this study, the sexual behavior of female MC4R knockout mice lacking melanocortin 4 receptors (MC4Rs) was examined. The mice were then bred to express MC4Rs exclusively on Sim1 neurons (tbMC4RSim1 mice) or on oxytocin neurons (tbMC4ROxt mice) to examine the effect on sexual responsiveness.

Results:

MC4R knockout mice were found to approach males less and have reduced receptivity to copulation, as indicated by a low lordosis quotient. These changes were independent of body weight. Lordosis behavior was normalized in tbMC4RSim1 mice and improved in tbMC4ROxt mice. In contrast, approach behavior was unchanged in tbMC4RSim1 mice but greatly increased in tbMC4ROxt animals. The changes were independent of melanocortin-driven metabolic effects.

Discussion:

These results implicate MC4R signaling in Oxt neurons in appetitive behaviors and MC4R signaling in Sim1 neurons in female sexual receptivity, while suggesting melanocortin-driven sexual function does not rely on metabolic neural circuits.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptor Tipo 4 de Melanocortina / Lordose Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptor Tipo 4 de Melanocortina / Lordose Idioma: En Ano de publicação: 2023 Tipo de documento: Article