The present study investigated the paracrine/autocrine role of prostaglandins in the development of the adipocyte phenotype. To determine the paracrine role of adipocyte-derived prostaglandins on differentiation of preadipocytes, test preadipocytes were cultured with medium conditioned by isolated mature adipocytes (ACM). ACM has been shown by our laboratory to contain factors released by mature adipocytes which induce differentiation. Addition of indomethacin, an inhibitor of prostaglandin synthesis, to the culture of adipocytes (ACM+I) significantly augmented differentiation induced by ACM. (p $\le$ 0.05). In contrast, addition of indomethacin to preadipocytes (ACM+Ia) resulted in significant inhibition of differentiation (p $\le$ 0.05) induced by ACM and standard differentiation mixture (MIX). These findings suggested that adipocytes secrete prostaglandins that may act as negative paracrine regulators of preadipocyte differentiation, whereas, preadipocytes may secrete prostaglandins that stimulate their differentiation in an autocrine manner. Cultured adipocytes and preadipocytes released PGI$\sb2$ and PGE$\sb2$ into medium. However, the amount of PGI$\sb2$ and PGE$\sb2$ released by preadipocytes was 1.4- and 11-fold greater than those released by adipocytes. When the effect of exogenous prostaglandins on preadipocyte differentiation was examined, PGI$\sb2$ and PGE$\sb2$ stimulated preadipocyte differentiation, but the effective concentration $({\ge}10\sp{-7}$ M) was much higher than the concentration found to be released in the culture medium of adipocytes. PGF$\sb{2\alpha},$ in contrast, inhibited differentiation significantly (p $\le$ 0.05) at a lower concentration $(10\sp{-8}$ M). These findings suggested that adipocytes may release PGE$\sb2$ and PGI$\sb2$ in amounts that are insufficient to stimulate preadipocyte differentiation. Hence the differentiating promoting activity of ACM cannot be due to the presence of PGI$\sb2$ or PGE$\sb2.$ (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/4290 |
| Date | January 1997 |
| Creators | Kumar, Veena A. |
| Contributors | Lau, D., |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Detected Language | English |
| Type | Thesis |
| Format | 89 p. |
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