Gonadotropin-releasing hormone (GnRH) is important in the control of reproduction, but its actions in non-reproductive processes are less well known. In this study we examined the effect of disrupting the GnRH receptor in mice to determine if growth, metabolism or behaviors that are not associated with reproduction were affected. To minimize the effects of other hormones such as FSH, LH and sex steroids, the neonatal-prepubertal period of 2 to 28 days of age was selected. The study shows that regardless of sex or phenotype in the Gnrhr gene knockout line, there was no significant difference in the daily development of motor control, sensory detection or spatial orientation among the wildtype, heterozygous or null mice. This included a series of behavioral tests for touch, vision, hearing, spatial orientation, locomotory behavior and muscle strength. Neither the daily body weight nor the final weight on day 28 of the kidney, liver and thymus relative to body weight varied significantly in any group. However by day 28, metabolic changes in the GnRH null females compared with wildtype females showed a significant reduction in inguinal fat pad weight normalized to body weight; this was accompanied by an increase in glucose compared with wildtype females shown by Student-Newman-Keuls Multiple Comparison test and Student's unpaired t tests. Our studies show that the GnRH-GnRHR system is not essential for growth or motor/sensory/orientation behavior during the first month of life prior to puberty onset. The lack of the GnRH-GnRHR axis, however, did affect females resulting in reduced subcutaneous inguinal fat pad weight and increased glucose with possible insulin resistance; the loss of the normal rise of estradiol at postnatal days 15–28 may account for the altered metabolism in the prepubertal female pups.

Pups.develop.behaviorDevelopmental behavior data for daily testing of mouse pups with GnRHR knock out. Tests for vision, touch, mobility, strength, and righting reflexes. Statistical assessment and figures generated using GraphPad Prism software. Used to generate Fig 2, 3, 4, & 5.Body wt.(tested vs untested mice)Developmental behavior data for daily testing of mouse pups with GnRHR knock out. Tests for body weight of animal tested daily vs animals not tested. Statistical assessment and figures generated using GraphPad Prism software. Used to generate Fig 6.Fat.kidney.liver.thymus % body weightDevelopmental behavior data for daily testing of mouse pups with GnRHR knock out. Tests for organ weight (% body weight) for inguinal, gonadal, scapular and retro-peritoneal fat pads, kidney, liver and thymus. Statistical assessment and figures generated using GraphPad Prism software. Used to generate Fig 7 & 9.Glucose.(tested vs untested mice)Developmental behavior data for daily testing of mouse pups with GnRHR knock out. Tests for blood glucose levels in tested and untested pups. Statistical assessment and figures generated using GraphPad Prism software. Used to generate Fig. 8.Body.wt.daily.2-28 - t-testsDevelopmental behavior data for daily testing of mouse pups with GnRHR knock out. Tests for daily body weights of experimental animals. Statistical assessment and figures generated using GraphPad Prism software. Used to generate Fig 1 T-test statistics.Body.wt.daily.2-28 - SNK testsDevelopmental behavior data for daily testing of mouse pups with GnRHR knock out. Tests for daily body weights of experimental animals. Statistical assessment and figures generated using GraphPad Prism software. Used to generate Fig 1 SNK statistics.