Detection and functional characterisation of the transcription factor peroxisome proliferator-activated receptor gamma in lutein cells

A prominent functional change during differentiation of lutein cells from f ollicular thecal and granulosa cells is an enhanced production and secretio n of progestins. The regulation of this process is not fully understood but may be associated with the expression of transcription factors which activ ate genes, products of which are involved in pathways of the cholesterol an d lipid metabolism. As peroxisome proliferator-activated receptors (PPARs) play a role in both pathways, we were interested in the expression of PPAR gamma, a PPAR form which is involved in adipogenic differentiation. First, we were able to show the expression of PPAR gamma in bovine lutein cells (d ay 12 of the ovarian cycle) at the mRNA and protein level by imaging, flow cytometry and blot analysis, and secondly a role of PPAR gamma in the secre tion of progesterone. The cells (24 h culture) responded dose dependently b y increasing progesterone secretion (up to 1.5-fold of the basal level) to an endogenous ligand of PPAR gamma, 15-deoxy-Delta(12,14) prostaglandin J(2 ) (15-dPGJ(2)) and to the thiazolidinedione ciglitizone. Aurintricarboxylic acid (ATA) was found to reduce the intracellular PPAR gamma level and to p romote cell cycle progress, indicating that ATA can be used as a tool for e xperimental changes of PPAR gamma proteins in intact cells and for studying the physiological consequences. The ATA-mediated decrease of PPAR gamma wa s accompanied by reduced progesterone production and a progression of the c ell cycle, suggesting a function of PPAR gamma in both processes. The respo nse to ATA was abrogated by a high dose (>490 nM) of 15-dPGJ(2), suggesting that 15-dPGJ(2) exerts its effect on steroidogenic activity via PPAR gamma and that the 15-dPGJ(2)-PPAR gamma system plays a role in the maintenance of a differentiated quiescent stage in lutein cells.