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 converge on the
20 alpha-HSD gene and control its expression in a dramatically 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 alpha-HSD,
PGF(2 alpha) stimulated and PRL inhibited PGF(2 alpha)-receptor,
phospholipase C delta(1) and
TGF beta(1) expression. In contrast PRL stimulated and
PGF(2 alpha) inhibited the
LH receptor,
11 beta-HSD2,
sterol carrier 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 alpha) 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 up-regulated the expression of the
sodium channel beta(1), Na/K
ATPase,
annexin IV, GST7pi, 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 synthase), as well as genes involved in tissue remodeling:
VEGF and TIMP3. PRL had a profound inhibitory effect on the expression of genes encoding the
ADP-ribosylation factor 3,
annexin V and c-jun, yet increased the expression of P450scc, 3beta-HSD, and SR-B1 (
HDL-receptor), all genes involved in steroidogenesis. PRL also stimulated the expression of beta(2)-microglobulin, TIMP2,
cytochrome c oxidase IV,
cathepsin H and L, and
copper-
zinc superoxide dismutase as well as
elongation factor SIII, heat shock protein-60 and
mitochondrial ATP synthase-D. In conclusion, this investigation has revealed a "yin-yang" relationship between PRL and
PGF(2 alpha) in regulating certain critical genes in the rodent CL, and has demonstrated novel regulation by these factors of other important genes involved in luteal function.