Ejaculatory abnormalities in mice lacking the gene for endothelial nitric oxide synthase (eNOS-/-).
Nitric oxide (NO) has been established as a neurotransmitter in both the central and peripheral nervous systems. Three isoforms of its synthetic enzyme, NO synthase (NOS), have been identified: 1) in the endothelial lining of blood vessels (eNOS), 2) an inducible form found in macrophages (iNOS), and 3) in neurons (nNOS). Previous studies using pharmacological agents that block all three isoforms of NOS have revealed that NO mediates several aspects of reproductive physiology and behavior, including anomalies in male sexual behavior and erectile function. To determine the specific contribution of the endothelial isoform of NOS in male reproductive behavior, we studied mice missing the gene for only eNOS (eNOS-/-). Wild-type (WT) and eNOS-/- animals were placed with an estrous WT female and observed for 45 min. Both WT and eNOS-/- mice displayed equivalent motivation to mount the stimulus female. However, eNOS-/- mice exhibited striking anomalies in ejaculatory function. A higher percentage of eNOS-/- than WT mice ejaculated during the testing period (p < 0.001). This increased propensity to ejaculate was apparently due to reduced stimulation required to elicit ejaculation; eNOS-/- mice required significantly fewer mounts (p < 0.003) and intromissions (p < 0.001) to ejaculate compared to WT mice. Taken together, these results suggest that NO synthesized by eNOS may be involved in ejaculatory physiology, but not sexual motivation.
Kriegsfeld
L J
LJ
Department of Psychology, The Johns Hopkins University, Baltimore, MD 21218-2686, USA.
Demas
G E
GE
Huang
P L
PL
Burnett
A L
AL
Nelson
R J
RJ
D000818:Animals; D004542:Ejaculation / Q000235:genetics* / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D009042:Motivation; D009154:Mutation / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D012726:Sexual Behavior, Animal / Q000502:physiology
D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse