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

Exposing growing oMt1a-oGH transgenic mice with the regulatable metallothio nein promotor to elevated growth hormone (GH) for three weeks after weaning enhances bone length and adipocyte differentiation. The objective of the p resent study was to investigate the consequences of highly elevated GH expo sure during fetal and early postnatal growth periods on the mature phenotyp e. Transgene expression, hence elevated GH, was achieved in fetuses and neo nates by providing 25 mM ZnSO4 to the drinking water of the dams. Wildtype and oMt1a-oGH male and female mice were a) never exposed to the transgene s timulus, 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 d uring the first 7 d postpartum. At 84 d of age when mature body size was re ached, ulna and humerus lengths, and body, liver gonadal fat pad, mesenteri c fat pad, and cleaned gastrointestinal (GI) tract weights were recorded. B one 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 adipo se content or bone lengths at maturity. However, chronic exposure to slight ly elevated GH, as seen in the transgenics never induced to express the tra nsgenic GH, depressed liver and GI weights and increased adipose depot weig hts and humerus lengths across both sexes. These results suggest that certa in tissues in the body, while capable of responding to GH during early deve lopmental periods, are not fully entrained to sustain that growth response once the GH stimulus is withdrawn. Further, the preadipocyte pool appears u nable to respond to GH early in development. Finally, the tissues examined exhibited a differential response to the GH suggesting that different tissu es possess distinct response thresholds.