Expression of insulin-like growth factor binding proteins (IGFBPs) before and during the hormone sensitive period of adipose tissue development in the fetal pig.

Abstract

The present study examined the influence of fetal age and thyroxine (T4) and growth hormone (GH) treatment, on the expression of insulin-like growth factor binding proteins (IGFBPs) in fetal pigs. On day 70 of gestation fetuses were either hypophysectomized (hypox), hypox and implanted with T4 pellets, or left intact, and were recovered 5, 10, 15 and 20 days following hypox and T4 pellet placement. Intact fetuses were also recovered from several dams at 50 days of gestation. In additional dams, hypox fetuses (day 70) were implanted with GH loaded Alzet mini-pumps on day 90, and control, untreated, and GH-treated hypox fetuses were recovered on day 105 of development. Subcutaneous adipose tissue, serum and other fetal tissues were collected at the time of recovery and prepared for subsequent ligand blot analysis with 125I -IGF-1 and immunoblot analysis with IGFBP antibodies. The main effect of IGFBP was significant (P <0.01) for age associated changes in serum IGFBP percentages. Between 50 and 75 days of fetal development the levels of 29 kDa IGFBPs in adipose tissue and serum markedly increased. In contrast, IGFBP-2 levels decreased and IGFBP-4 levels increased in adipose tissue while IGFBP-2 levels increased and levels of IGFBP-4 and -3 decreased in serum. Fetal hypox decreased adipose tissue IGFBP levels in a time and IGFBP-dependent manner. For instance, IGFBP-2 and 29 kDa IGFBP levels decreased much faster after fetal hypox than did IGFBP-3 levels whereas IGFBP-4 levels did not decrease. The main effect of IGFBP was significant (P<0.01) for T4-induced changes in adipose tissue IGFBP levels. T4 treatment increased adipose tissue levels of 29 kDa IGFBPs but did not influence IGFBP-2,-3 and -4 levels. GH treatment had no influence on adipose tissue or serum IGFBP levels. These studies indicate that IGFBP-1 (one of the 29 kDa IGFBPs) may be the major IGFBP mediator of the influence of T4 on fetal development.