Opposite effect of prolactin and prostaglandin F-2 alpha on the expressionof luteal genes as revealed by rat cDNA expression array

It is well established that prolactin (PRL) sustains, while prostaglandin F -2 alpha (PGF(2 alpha)) curtails, progesterone production by the rat corpus luteum (CL). We have previously shown that the actions of both molecules c onverge on the 20 alpha -HSD gene and control its expression in a dramatica lly opposed manner. In this investigation, we have found twelve more genes that are inversely regulated by PRL and PGF(2 alpha). In addition to 20 alp ha -HSD, PGF(2 alpha) stimulated and PRL inhibited PGF(2 alpha)-receptor, p hospholipase C delta (1) and TGF beta (1) expression. In contrast PRL stimu lated and PGF(2 alpha) inhibited the LH receptor, 11 beta -HSD2, sterol car rier protein 2, mitochondrial glutathione S-transferase (GST), GST mu (2), inhibitory DNA-binding proteins 1, 2, and 3, and calcium binding protein 2. We have also identified new target genes for PRL and PGF(2 alpha). PGF(2 a lpha) stimulated the expression of genes involved in cell signaling such as cell adhesion kinase-beta, ERK3, FRA2, IL-2 receptor, and 14-3-3 proteins. PGF(2 alpha) also upregulated the expression of the sodium channel beta (1 ), Na/K ATPase, annexin IV, GST7 pi, and P450 reductase. in contrast PGF(2 alpha) inhibited the expression of two genes involved in cell cycle: cyclin D2 and retinoblastoma related protein (Rb2/p130). It also inhibited genes involved in estradiol (P-450(AROM)) and cholesterol biosynthesis (HMG-CoA s ynthase), as well as genes involved in tissue remodeling: VEGF and TIMP3. P RL had a profound inhibitory effect on the expression of genes encoding the ADP-ribosylation factor 3, annexin V and c-jun, yet increased the expressi on of P450scc, 3 beta -HSD, and SR-BI (HDL-receptor), all genes involved in steroidogenesis. PRL also stimulated the expression of beta (2)-microglobu lin, TIMP2, cytochrome c oxiclase IV, cathepsin H and L, and copper-zinc su peroxide dismutase as well as elongation factor SIII, heat shock protein-60 and mitochondrial ATP synthase-D. In conclusion, this investigation has re vealed a "yin-yang" relationship between PRL and PGF(2 alpha) in regulating certain critical genes in the rodent CL, and has demonstrated novel regula tion by these factors of other important genes involved in luteal function.