Submitted to: Growth Development and Aging
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/12/2002
Publication Date: 7/16/2002
Citation: HAUSMAN, G.J., RICHARDSON, R.L., SIMMEN, F.A. SECRETION OF INSULIN-LIKE GROWTH FACTOR (IGF)-I AND-II AND IGF BINDING PROTEINS (IGFBPS) IN FETAL STROMAL-VASCULAR (S-V) CELL CULTURES OBTAINED BEFORE AND AFTER THE ONSET OF ADIPOGENESIS IN VIVO.. GROWTH DEVELOPMENT AND AGING. 2002. v. 66. p. 11-26. Interpretive Summary: Glucocorticoids induce fat cell development and down regulate all four major insulin-like growth factor (IGF) binding proteins (IGFBPs) and IGF-I in cultures of fat cell precursors from young pigs. Results of this study clearly indicate that the capability of glucocorticoids to induce fat cell development and down regulate IGFBP and IGF-I secretion by fat cell precursor cells develops with age. In particular, down regulation of IGFBP-3 may augment fat cell development since IGFBP-3 can act as a growth factor per se. Therefore, the absence of fat cell development in growth hormone treated pigs despite increased IGF-1 levels may be attributable to antagonism of adipogenesis by increased IGFBP-3 levels. Further study is necessary to examine potential relationships between fat deposition in pigs and the expression of IGFBP-3 by fat cells and fat cell precursors.
Technical Abstract: The present study examined the influence of dexamethasone (DEX) treatment on preadipocyte recruitment and differentiation and insulin-like growth factor binding protein (IGFBP) secretion in stromal- vascular (S-V) cell cultures established from fetuses and young pigs. Three 105 day, two 85 day, nine 75 day and four 50 day fetal S-V cultures were studied with each fetal S-V cell culture representing 1 pool of S-V cells/dam. We also studied four S-V cell cultures from each of four young pigs (5-7 days old). Cultures were seeded and plated in 10% FBS from d 0-3 and treated with insulin (ITS) + 10 nM DEX from d 3-6. Alternatively, cultures were seeded and plated in 10% FBS + 80 nM DEX from d 0-3 and treated with insulin alone from d 3-6 (FBS + DEX). Conditioned media was collected on day 6 of culture, 3 days of conditioning, and prepared for subsequent **125 I-IGF-1 ligand blot analysis for IGFBPs and RIA for IGF-I and IGF-II. Insulin + DEX Xand FBS + DEX increased (P less than .05) preadipocyte (AD-3+) recruitment but only FBS + DEX increased preadipocyte differentiation (lipid + and C/EBP alpha +) by day six in 75 day fetal S-V cultures. Insulin + DEX reduced levels of 29 kDa IGFBPs and markedly increased (P less than .05) IGFBP-3 levels in 75 day S-V media. Insulin + DEX also markedly increased (P less than .05) IGFBP-3 levels in 50 day S-V media but had little influence on other IGFBPs. FBS + DEX treatment increased (P less than .05) IGFBP-4 levels in 75 day S-V media but had little to no influence on levels of IGF-I, IGF-II and other IGFBPs. These studies indicate that IGFBP-3 may antagonize preadipocyte differentiation by targeting IGF-I away from differentiating cells and towards growing cells.