Inhibitory effect of a new steroidal saponin, OSW-1, on ovarian functions in rats

1 This study was undertaken to determine the effects of OSW-1 13 beta, 16 beta, 17 alpha-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoly-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 mu g 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 mu g 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 mu g kg(-1) OSW-1, the serum oestradiol (E-2) levels at the expected next prooestrus were significantly lower than in control (pro-oestrus). The serum luteinizing hormone (LH) levels 4 days after 9 mu g kg(-1) OSW-1 treatment were also markedly lower than those of control. OSW-1 (4.5 mu g 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 (p45Oscc), an ovarian steroidal limiting enzyme, was suppressed at 24 and 96 h after OSW-1 treatment. 6 Administration of OSW-1 (9 mu g 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 E-2 secretion and that the decrease in E-2 secretion mag. 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.