AUTOCRINE CONTROL OF ADIPOSE CELL-DIFFERENTIATION BY PROSTACYCLIN AND PGF2-ALPHA

The mitogenic-adipogenic effect exerted by arachidonic acid, which leads to terminal differentiation of Ob1771 mouse preadipocytes, has been shown to be (i) blocked by cyclooxygenase inhibitors, (ii) mimicked by a stable analogue of prostacyclin (carbaprostacyclin) and (iii) potentiated by PGF2-alpha. Since these prostanoids are known to be synthesized and secreted by preadipocytes, we have proposed that both prostacyclin as the key mediator and PGF2-alpha as a modulator control the expression of terminal events of adipose conversion by means of an autocrine mechanism (Gaillard, D. et al. and Negrel, R. et al. Biochem. J. (1989) 257, 389-397 and 399-405). In order to test this hypothesis, the release of prostacyclin, characterized under the form of its stable degradation product 6-keto-PGF1-alpha, and that of PGF2-alpha have been studied in the culture medium of Ob1771 cells. A striking increase in the release of 6-keto-PGF1-alpha and to a minor degree of PGF2-alpha was observed when cells were exposed to arachidonic acid as shown by using [H-3]arachidonic acid prelabelled cells or by radio-immunoassays. Since antagonists of PGF2-alpha and PGI2 receptors were not available, specific antibodies directed against PGF2-alpha and 6-beta-PGI1, another stable analogue of prostacyclin, were added as neutralizing agents in the culture medium. These antibodies were able to counteract the mitogenic-adipogenic effect of arachidonic acid. Prostacyclin and PGF2-alpha thus appear as autocrine mediators in the process of adipose conversion.