Influence of Thyroxine In Vivo on Preadipocyte Development and Insulin‐Like Growth Factor‐I and IGF Binding Protein Secretion in Fetal Stromal Vascular Cell Cultures

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Abstract
Studies were conducted to determine the influence of thyroxine (T4) in vivo on preadipocyte development and insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs) secretion in stromal-vas-cular (S-V) cultures. Fetal pigs were hypophysectomized (hypox) at 70 days of gestation, implanted with T4 pellets, and fetuses from the dam at 75 days of gestation. In a second experiment, hypox and T4 implantation were performed at 75 days and fetal pigs removed at 95 days of gestation. Primary cultures of stromal vascular (S-V) cells derived from fetal adipose tissue were established. Cultures were stained for morphological analysis and conditioned media were collected for IGF-I determination by radioimmunoassay (RIA) and IGFBP analysis by Western blotting. After only 5 days of T4 treatment, fat cell cluster number and size and lipid deposition in cultures were significantly increased compared to cultures from untreated hypox fetuses. Fetal hypox reduced IGF-I secretion by preadipocytes at both ages and T4 treatment completely normalized IGF-I secretion (p < 0.05). Four IGFBPs (BP-1, BP-2, BP-3 & BP-4) detected in S-V cultures derived from 95-day fetuses were decreased in concentration by hypox by 44 ± 9.4%, 32 ± 9.7%, 42 ± 12% and 53 ± 6.9%. In cultures derived from T4 treated hypox fetuses, the levels of these four IGFBPs were increased by 187 ± 25%, 239 ± 38%, 190 ± 5% and 347 ± 43% over control values, respectively. In cultures from 75-day fetuses, only IGFBP-2 (major one) and BP-1 (minor one) were detected and their secretion was also decreased by hypox and elevated by T4 treatment (190 ± 49.5%, 156 ± 30%, respectively, of controls). The results provide direct evidence that T4 has a major influence on fetal preadipocyte development. T4 stimulated production of IGF-I and IGFBP in fetal S-V cultures, which in turn, may have mediated the capability of T4 to enhance fetal adipose tissue development.