The interaction of hydrocortisone and thyroxine during fetal adipose tissue differentiation: CCAAT enhancing binding protein expression and capillary cytodifferentiation.

Late-term fetal pigs from genetically obese dams have elevated levels of thyroid hormones and glucocorticoids, depressed levels of GH, larger fat cells and elevated lipogenesis than do fetal pigs from lean dams. We investigated the influence of elevated levels of thyroid hormones and glucocorticoids per se on adipose tissue traits by chronically treating hypophysectomized (hypox; d 70) fetal pigs between d 90 and 105 of gestation with either thyroxine (T4), hydrocortisone (HC), or the combination of T4 + HC. Treatment with T4 and T4 + HC increased serum T4 and IGF-I levels and enhanced skin and hair development. Treatment with HC and T4 + HC increased serum HC levels, fat cell size, and inner subcutaneous adipose tissue thickness. Quantitative analysis of stained adipose tissue sections indicated that T4 + HC treatment increased lipid accretion and fat cell cluster development more than did either hormone alone. The T4 + HC markedly increased apparent fat cell number, because there was only a 19% increase in fat cell size. A hypox-induced deficit in cytodifferentiation of capillaries associated with adipocytes was not influenced by T4, but was partially normalized by treatment with HC and T4 + HC. Immunocytochemical and Western blot analyses showed no influence of hormonal treatment on expression of three CCAAT enhancing binding protein (C/EBP) isoforms. However, expression of C/EBPdelta in adipose tissue was markedly reduced in control fetal pigs compared with hypox fetal pigs. These studies indicate that concurrent action of glucocorticoids and thyroid hormones may be the critical aspect of endocrine regulation of fetal adipogenesis.