Effects of pre and antenatal elevated and chronic oMt1a-oGH transgene expression on adipose deposition and linear...

Exposing growing oMtla-oGH transgenic mice with the regulatable metallothionein promotor to elevated growth hormone (GH) for three weeks after weaning enhances bone length and adipocyte differentiation. The objective of the present study was to investigate the consequences of highly elevated GH exposure during fetal and early postnatal growth periods on the mature phenotype. Transgene expression, hence elevated GH, was achieved in fetuses and neonates by providing 25 mM ZnSO4 to the drinking water of the dams. Wildtype and oMtla-oGH male and female mice were a) never exposed to the transgene stimulus, b) exposed from birth to 21 d of age, c) exposed through gestation until 21 d of age, d) exposed only through gestation, or e) exposed only during the first 7 d postpartum. At 84 d of age when mature body size was reached, ulna and humerus lengths, and body, liver gonadal fat pad, mesenteric fat pad, and cleaned gastrointestinal (GI) tract weights were recorded. Bone lengths were also determined in a subset of mice at 22 d of age. While early exposure to the elevated GH increased ulna and humerus length at 22 d of age, the early GH levels failed to produce significant changes in adipose content or bone lengths at maturity. However, chronic exposure to slightly elevated GH, as seen in the transgenics never induced to express the transgenic GH, depressed liver and GI weights and increased adipose depot weights and humerus lengths across both sexes. These results suggest that certain tissues in the body, while capable of responding to GH during early developmental periods, are not fully entrained to sustain that growth response once the GH stimulus is withdrawn. Further, the preadipocyte pool appears unable to respond to GH early in development. Finally, the tissues examined exhibited a differential response to the GH suggesting that different tissues possess distinct response thresholds.