Evidence for a Luteotropic Role of Peroxisome Proliferator-Activated Receptor Gamma: Expression and In Vitro Effects on Enzymatic and Hormonal Activities in Corpora Lutea of Pseudopregnant Rabbits.

The expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and its role in corpora lutea (CL) function were studied in pseudopregnant rabbits. CL were collected at early (Day 4), mid (Day 9), and late (Day 13) stages of pseudopregnancy. Immunohistochemistry evidenced the presence of PPARgamma in the perinuclear cytoplasm and nucleus of all luteal cells; immunoreactivity decreased from early to late stage, with immunonegativity of the nuclei of late CL. PPARgamma mRNA transcript was expressed in all luteal stages with the lowest level at late stage. In CL cultured in vitro, PPARgamma agonist (15-deoxy delta12,14 prostaglandin J2, 15d-PGJ2, 200 nM) increased and antagonist (T0070907, 50 nM) decreased progesterone secretion at early and mid luteal stages, whereas 15d-PGJ2 reduced and T0070907 increased PGF2alpha ones. Prostaglandin-endoperoxide synthase 2 (PTGS2) activity was reduced by 15d-PGJ2 and increased by T0070907 in corpora lutea of early and mid luteal stages. Conversely, 15d-PGJ2 increased and T0070907 reduced 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity in early and mid luteal stage CL. PGE2 in vitro secretion as well as PTGS1 and 20alpha-HSD enzymatic activities were not affected by 15d-PGJ2 and T0070907 in any CL types. These results indicate that PPARgamma plays a luteotropic role in pseudopregnant rabbits, through PTGS2 down-regulation and 3beta-HSD up-regulation, with consequent PGF2alpha decrease and progesterone increase