Effects of GH deficiency and GH replacement on inter-male aggressiveness in mice

Abstract Objective Growth hormone (GH) has been suggested to influence aggressive behavior in several species, but no data are presently available in GH-deficient (GHD) animals. The aim of this study was to elucidate the effects of GHD on aggressive behavior in a mouse model of isolated GHD due to removal of the GHRH gene (GHRH knock out, GHRHKO), and to evaluate the effects of GH replacement. Design We studied two groups of adult male mice: Ten GH-sufficient animals heterozygous for GHRHKO allele (HTZ), and 30 GHRHKO animals. Behavior was measured by scoring several aggression parameters after isolation, when the animal was challenged against an intruder both in neutral and home cage. Animals were then re-studied after the GHRHKO mice were left untreated (control, Ctrl), or were treated for 2 weeks with daily subcutaneous recombinant GH or with vehicle (Veh). Blood samples were collected before and after GH or Veh treatment, and assayed for serum IGF-I and testosterone. Results The GHRHKO mice showed significantly reduced aggressiveness compared to HTZ animals. GH (but not Veh) administration normalized isolation-induced aggressive behavior in GHRHKO mice, despite lack of full serum IGF-I normalization. No difference was noted in serum testosterone levels among all groups at any of the time points. Conclusions These findings show that GHD reduces aggressive behavior in GHRHKO mice, that GH replacement normalizes aggressiveness, and that this behavior change is not related to an increase in serum testosterone.