A role for the melanocortin 4 receptor in sexual function.
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.
Van der Ploeg
Lex H T
LH
Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA. lex_van_der_ploeg@merck.com
Martin
William J
WJ
Howard
Andrew D
AD
Nargund
Ravi P
RP
Austin
Christopher P
CP
Guan
Xiaoming
X
Drisko
Jennifer
J
Cashen
Doreen
D
Sebhat
Iyassu
I
Patchett
Arthur A
AA
Figueroa
David J
DJ
DiLella
Anthony G
AG
Connolly
Brett M
BM
Weinberg
David H
DH
Tan
Carina P
CP
Palyha
Oksana C
OC
Pong
Sheng-Shung
SS
MacNeil
Tanya
T
Rosenblum
Charles
C
Vongs
Aurawan
A
Tang
Rui
R
Yu
Hong
H
Sailer
Andreas W
AW
Fong
Tung Ming
TM
Huang
Cathy
C
Tota
Michael R
MR
Chang
Ray S
RS
Stearns
Ralph
R
Tamvakopoulos
Constantin
C
Christ
George
G
Drazen
Deborah L
DL
Spar
Brian D
BD
Nelson
Randy J
RJ
MacIntyre
D Euan
DE
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*
D017931:DNA Primers; D018076:DNA, Complementary; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D012259:Ribonuclease, Pancreatic