Consequences of limited exposure to elevated growth hormone in the mature oMt1a-oGH transgenic mouse

Abstract

Male and female transgenic mice carrying the regulatable ovine metallothionein-ovine growth hormone (oMt1a-oGH) transgene were exogenously induced to express elevated GH at maturity. Male transgenics responded to continuously elevated GH with smaller white adipose tissue depots (WAT); cessation of transgene stimulation with restoration of basal circulating GH ablated the improvement in WAT. Transgenic males in which the transgene was never exogenously activated expressed low levels of oGH (60.2 ng/ml) and this low, chronic level resulted in 30-50% larger (p < 0.05) gonadal, inguinal, and mesenteric WAT relative to all wildtype controls, transgenics actively expressing the transgene, or transgenics exposed to elevated GH for a limited time. Mature females continued to accrue body mass proportional to circulating GH. Similar to that observed in the males, transgenic females in which the transgene was never exogenously activated exhibited enlarged WAT that were 20-40% larger than the same depots in wildtype control females. However, in contrast to the data for the males, transgenic females that had experienced a four week exposure to elevated GH followed by a return to basal conditions tended to have the greatest WAT depots (p < 0.10). This would indicate that female adipocytes are still capable of responding to elevated GH with proliferation/differentiation at maturity. These data support the hypothesis that the generalized sexual dimorphic pattern of lipid deposition may be attributed to the sexually dimorphic pattern of GH experienced by the two sexes.