Transforming growth factor-alpha (TGF alpha) and prostaglandin F2 alpha (PGF2 alpha) are potent inhibitors of adipocyte differentiation. We demonstrate here that TGF alpha messenger RNA (mRNA) is expressed in freshly isolated fat pads and in primary culture of adipocyte precursors cultivated in defined medium before and after differentiation. We show that PGF2 alpha stimulated TGF alpha mRNA expression in a dose-dependent manner. PGF2 alpha also stimulated TGF alpha production in the culture medium of adipocyte precursors in primary culture. PGF2 alpha stimulated TGF alpha mRNA expression in both undifferentiated and differentiated cells. 9 alpha,11 beta-PGF2 alpha, which also inhibited adipose differentiation, stimulated TGF alpha mRNA expression similarly to PGF2 alpha, whereas other PGs had no effect on TGF alpha mRNA expression. The time-course experiment indicates that the stimulation of TGF alpha mRNA expression by PGF2 alpha is observed within 6 h of exposure to PGF2 alpha and is inhibited by treatment of the cells with actinomycin D. The effect of PGF2 alpha on TGF alpha expression did not require activation of protein kinase C and was fully reversible. As both TGF alpha and PGF2 alpha are inhibitors of adipose differentiation, it is suggested that stimulation of TGF alpha expression by PGF2 alpha could represent an amplification mechanism to modulate adipocyte precursor differentiation and adipocyte function within the adipose tissue.