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Small Nuclear RING Finger Protein Expression during Gonad Development: Regulation by Gonadotropins and Estrogen in the Postnatal Ovary

Biomedicum Helsinki, Institute of Biomedicine (Physiology) (S.J.H.-S., J.J.P., O.A.J.), Department of Clinical Chemistry (O.A.J.), Program for Developmental and Reproductive Biology (M.A., M.H.), University of Helsinki, FIN-00014 Helsinki, Finland; Hospital for Children and Adolescents (M.A., M.H.), Helsinki University Central Hospital, FIN-00290 Helsinki, Finland; Institute of Biomedicine, Department of Anatomy (S.S.), University of Turku, FIN-20520 Turku, Finland; and Department of Molecular and Cellular Biology (V.S., J.S.R.), Baylor College of Medicine, Houston, Texas 77030

Address all correspondence and requests for reprints to: Dr. Olli A. Jänne, Biomedicum Helsinki, Institute of Biomedicine (Physiology), University of Helsinki, P.O. Box 63, FIN-00014 Helsinki, Finland.E-mail: olli.janne{at}helsinki.fi.

Small nuclear RING finger protein (SNURF/RNF4) is a steroid receptor coregulator that is down-regulated in testicular germ cell cancer. In this work, we examined SNURF expression during murine fetal gonad development and postnatal ovarian folliculogenesis by in situ hybridization and immunohistochemical staining. SNURF mRNA was detectable in gonads of both sexes from embryonic 10.5 days post conception onward. SNURF protein localized to gonocytes and somatic Leydig and Sertoli cells of fetal testis and in oogonia and supporting cells of fetal ovary. In murine postnatal ovary, SNURF mRNA and protein were expressed throughout folliculogenesis, peaking in the oocytes of preantral follicles. Lower amounts of SNURF mRNA and protein were also present in granulosa cells of secondary, antral, and preovulatory follicles and in luteal glands. Exposure of immature female mice and rats to gonadotropin from pregnant mare serum and human chorionic gonadotropin did not change dramatically SNURF mRNA levels in ovary. SNURF mRNA expression was increased in ovaries of immature mice treated with diethylstilbestrol, an effect that was blocked by the pure antiestrogen ICI 182,780. SNURF protein was constitutively expressed in oocytes of hypophysectomized rats, and its content was augmented by estradiol in granulosa cells. In granulosa cell culture, SNURF mRNA accumulation was transiently increased by treatment with the LH agonists phorbol myristate and forskolin at 4 h after treatment and at 48 h in differentiated cells expressing markers of the preovulatory phenotype. These results suggest a role for SNURF in fetal germ cell development as well as in oocyte and granulosa cell maturation in an estrogen- and gonadotropin-regulated fashion.

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