Messenger ribonucleic acids for MAC25 and connective tissue growth factor (CTGF) are inversely regulated during folliculogenesis and early luteogenesis

Cell proliferation, terminal differentiation, and angiogenesis occur during cycles of follicular and luteal development. In other paradigms, mac25, a potent tumor inhibitor is strongly induced in senescent epithelial cells, w hereas CTGF stimulates angiogenesis and wound healing. Using in situ hybrid ization and immunohistochemistry, we have examined the possibilities that m ac25 is inhibited, whereas CTGF is induced during active periods of follicu lar development and luteogenesis. Ovaries were collected during the follicu lar and early luteal phases from prostaglandin F2 alpha-treated mature pigs and from slaughterhouse sows. CTGF transcripts were induced during the lat e preantral stage in granulosa and theca cells coneomitantly with the appea rance of endothelial cells in the theca. CTGF mRNA expression increased in granulosa cells to a maximum (P < 0.01) in mid-antral follicles but was dow n regulated (P < 0.01) in preovulatory follicles. In contrast, granulosa ce ll mac25 mRNA expression was undetectable between the preantral and mid-ant ral stage but was strongly induced in terminally differentiated granulosa c ells of preovulatory follicles. CTGF mRNA and peptide were also detected in the theca externa/interstitium and in vascular endothelial cells of ovaria n blood vessels, whereas mac25 transcripts, which were also abundant in ova rian blood vessels increased in the theca interna with follicular developme nt. Transcripts of cyclin D1, a marker of cell proliferation, appeared duri ng the early antral stage and were moderate in granulosa cells but abundant in capillary endothelial cells in the theca interna, underneath the baseme nt membrane, Following ovulation, CTGF and cyclin D1 mRNAs were associated with the migration of endothelial cells into the CL. Subsequently, there wa s a marked up-regulation of CTGF mRNA expression in granulosa luteins conco mitantly with an increase in endothelial cell proliferation within the CL. We hypothesize that CTGF may promote ovarian cell growth and blood vessel f ormation during follicular and luteal development whereas mac25, a tumor in hibitor, may promote terminal differentiation of granulosa cells in preovul atory follicles.