title: A role for the melanocortin 4 receptor in sexual function.
abstract: By using a combination of genetic, pharmacological, and anatomical approaches, we show that the melanocortin 4 receptor (MC4R), implicated in the control of food intake and energy expenditure, also modulates erectile function and sexual behavior. Evidence supporting this notion is based on several findings: (i) a highly selective non-peptide MC4R agonist augments erectile activity initiated by electrical stimulation of the cavernous nerve in wild-type but not Mc4r-null mice; (ii) copulatory behavior is enhanced by administration of a selective MC4R agonist and is diminished in mice lacking Mc4r; (iii) reverse transcription (RT)-PCR and non-PCR based methods demonstrate MC4R expression in rat and human penis, and rat spinal cord, hypothalamus, brainstem, pelvic ganglion (major autonomic relay center to the penis), but not in rat primary corpus smooth muscle cavernosum cells; and (iv) in situ hybridization of glans tissue from the human and rat penis reveal MC4R expression in nerve fibers and mechanoreceptors in the glans of the penis. Collectively, these data implicate the MC4R in the modulation of penile erectile function and provide evidence that MC4R-mediated proerectile responses may be activated through neuronal circuitry in spinal cord erectile centers and somatosensory afferent nerve terminals of the penis. Our results provide a basis for the existence of MC4R-controlled neuronal pathways that control sexual function.
authors.affiliation: Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA. lex_van_der_ploeg@merck.com
authors.forename: Lex H T
authors.initials: LH
authors.lastname: Van der Ploeg
authors.forename: William J
authors.initials: WJ
authors.lastname: Martin
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Howard
authors.forename: Ravi P
authors.initials: RP
authors.lastname: Nargund
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Austin
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Guan
authors.forename: Jennifer
authors.initials: J
authors.lastname: Drisko
authors.forename: Doreen
authors.initials: D
authors.lastname: Cashen
authors.forename: Iyassu
authors.initials: I
authors.lastname: Sebhat
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Patchett
authors.forename: David J
authors.initials: DJ
authors.lastname: Figueroa
authors.forename: Anthony G
authors.initials: AG
authors.lastname: DiLella
authors.forename: Brett M
authors.initials: BM
authors.lastname: Connolly
authors.forename: David H
authors.initials: DH
authors.lastname: Weinberg
authors.forename: Carina P
authors.initials: CP
authors.lastname: Tan
authors.forename: Oksana C
authors.initials: OC
authors.lastname: Palyha
authors.forename: Sheng-Shung
authors.initials: SS
authors.lastname: Pong
authors.forename: Tanya
authors.initials: T
authors.lastname: MacNeil
authors.forename: Charles
authors.initials: C
authors.lastname: Rosenblum
authors.forename: Aurawan
authors.initials: A
authors.lastname: Vongs
authors.forename: Rui
authors.initials: R
authors.lastname: Tang
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Sailer
authors.forename: Tung Ming
authors.initials: TM
authors.lastname: Fong
authors.forename: Cathy
authors.initials: C
authors.lastname: Huang
authors.forename: Michael R
authors.initials: MR
authors.lastname: Tota
authors.forename: Ray S
authors.initials: RS
authors.lastname: Chang
authors.forename: Ralph
authors.initials: R
authors.lastname: Stearns
authors.forename: Constantin
authors.initials: C
authors.lastname: Tamvakopoulos
authors.forename: George
authors.initials: G
authors.lastname: Christ
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Drazen
authors.forename: Brian D
authors.initials: BD
authors.lastname: Spar
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Nelson
authors.forename: D Euan
authors.initials: DE
authors.lastname: MacIntyre
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003307:Copulation / Q000502:physiology*; D017931:DNA Primers; D018076:DNA, Complementary; D004558:Electric Stimulation; D004734:Energy Metabolism / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007427:Intracranial Pressure / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009412:Nerve Fibers / Q000502:physiology; D010413:Penis / Q000294:innervation / Q000502:physiology*; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012259:Ribonuclease, Pancreatic; D012726:Sexual Behavior, Animal / Q000502:physiology*
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D012259:Ribonuclease, Pancreatic