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LUTEAL NITRIC OXIDE DOWN-REGULATES STEROIDOGENESIS BY THE CORPUS LUTEUM AT THE TIME OF PARTURITION IN THE RAT.
Yang, Hyunwon1, Saleem, Shareefah2, Bhat, Ganapathy1, Chung, Brian1, Sridaran, Rajagopala1, 1 2
ABSTRACT- Progesterone secreted by the corpus luteum (CL) is critical to maintain pregnancy in the rat. Progesterone levels during pregnancy increase in mid term and then rapidly decrease at the time of parturition. To elucidate the mechanism(s) by which progesterone secretion decreases at the time of parturition, we investigated nitric oxide (NO) as a regulating factor to control the steroidogenesis in the CL. Rats were sacrificed on day 8, 10, 12, 14, 18, 20, 22, of pregnancy and hours after the parturition to collect serum and the CL. Serum progesterone and intraluteal NO levels were measured by a radioimmunoassay and a colorimetric assay, respectively. Endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and neuronal synthase (nNOS) were detected by immunoblot and immunohistochemistry. Intraluteal NO levels started increasing from day 18 with peak levels occurring at the time of parturition, whereas progesterone levels started decreasing from day 16 with nadir levels occurring around the time of parturition. Immunoblot and immunohistochemical data of iNOS and eNOS in the CL showed that the increase in luteal NO levels was associated with an increase in iNOS protein, but not in eNOS protein. In addition, we demonstrated, for the first time, the presence of nNOS protein in the CL of the pregnant rat, which also correlated with the increase in luteal NO levels. The results of the present study demonstrate that the reduction in serum progesterone at the time of parturition relate in part to the increase in NO synthesis via eNOS and nNOS. These date suggest that NO could regulate the steroidogenesis of the CL in the pregnant rat. (Supported by grants S06-GM08248 from NIH and NAG 9-963 from NASA).
KEY WORDS: Nitric oxide, Steroidogenesis, Corpus luteum, Pregnancy