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Inhibitory effect of a new steroidal saponin, OSW-1, on ovarian functions in rats
1Department of Pharmacology, Tokyo University of Pharmacy & Life Science, Japan.
Abstract:
1. This study was undertaken to determine the effects of OSW-1 (3 beta, 16 beta, 17 alpha-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-beta-D-xylopyranosyl)- (1-->3)-(2-O-acetyl-alpha-L-arabinopyranoside)) on the pituitary-ovarian system and the functions of aortic smooth muscle. 2. A single s.c. injection of OSW-1 (9 micrograms kg-1) on the morning of pro-oestrus inhibited the occurrence of the expected next pro-oestrus, whereas administration of OSW-1 at a dose of 4.5 micrograms kg-1 did not affect the oestrous cycle. OSW-1 treatment on the day of dioestrus-1 did not affect the oestrous cycle. 3. At doses of 4.5 and 9 micrograms kg-1 OSW-1, the serum oestradiol (E2) levels at the expected next pro-oestrus were significantly lower than in control (pro-oestrus). The serum luteinizing hormone (LH) levels 4 days after 9 micrograms kg-1 OSW-1 treatment were also markedly lower than those of control. OSW-1 (4.5 micrograms kg-1) did not affect the levels of inhibin, progesterone and gonadotrophins on the same day. 4. OSW-1 did not inhibit the preovulatory LH surge which occurs on the afternoon of pro-oestrus day. 5. The expression of mRNA coding for the cholesterol side chain cleavage cytochrome P-450 (p450scc), an ovarian steroidal limiting enzyme, was suppressed at 24 and 96 h after OSW-1 treatment. 6. Administration of OSW-1 (9 micrograms kg-1) tended to reduce the relaxation of isolated thoracic aorta ring preparations induced by acetylcholine, while there was no difference in the relaxation induced by sodium nitroprusside. 7. Our results show that OSW-1 inhibits ovarian E2 secretion and that the decrease in E2 secretion may contribute to its effects on the oestrous cycle and the sensitivity of the thoracic aorta to relaxation. The decrease in the levels of ovarian steroids induced by OSW-1 may be due to its direct inhibitory action on the gene expression of the steroidal enzyme and on the proliferation of granulosa cells in the ovary.