Stimulation of Hepatic Insulin-Like Growth Factor-I Gene Expression by Ovine Prolactin: Evidence for Intrinsic Somatogenic Activity in the Rat*

Abstract

The effect of ovine PRL (oPRL) on hepatic insulin-like growth factor I (IGF-I) gene expression was examined in the hypophysectomized (hypox) rat and compared with that seen in hypox rats treated with ovine GH (oGH) and human GH (hGH). A single injection of oPRL (100 micrograms/100 g BW) resulted in a 15-fold increase in hepatic IGF-I messenger RNA abundance 12 h after administration. Serum IGF-I increased from 82.9 +/- (SE) 9.0 to 137.0 +/- 15.4 ng/ml. In acute studies, where the slopes of 4-point dose-response curves were compared, oPRL was approximately 50% as potent as oGH in stimulating serum IGF-I and hepatic IGF-I messenger RNA accumulation. In chronic experiments, where a single daily injection of oPRL (0, 10, 30, or 90 micrograms/day) was administered for 10 days, a significant increase in body wt was observed at each dose. However, in contrast to hypox rats which received oGH, no dose-response relationship was apparent, and oPRL was less than 10% as potent as oGH in this regard. A small but significant increase in serum IGF-I and hepatic IGF-I expression was observed in hypox rats chronically injected with oPRL when killed 6-7 h after the final injection. However, by extrapolation from the hGH dose-response curves, oPRL was 6.8% and 22.7% as potent as hGH in stimulating serum IGF-I and hepatic IGF-I accumulation respectively. The observations reported here demonstrate that oPRL has significant somatogenic activity in the rat as determined by the three variables measured. Whereas oPRL had significant effects on body weight gain, serum IGF-I and hepatic IGF-I expression, the potency of oPRL by comparison with the two other somatogenic hormones was more marked in acute experiments compared to the effects seen after chronic administration. These results suggest that oPRL, like human GH, has both somatogenic and lactogenic activity in the rat and therefore may be an inappropriate control in studies of the effects of somatogenic hormones in the rat.