Kotaro Takasaki

Inhibitory and stimulatory actions of danazol in rat ovarian and uterine tissues.

We examined whether danazol has a direct action on ovarian steroid secretion and/or uterine prostaglandin (PG) F2 alpha catabolic activity in immature rats in which the first ovulation was induced and in adult ovariectomized rats. The preovulatory surge of estradiol and progesterone was markedly suppressed together with that of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by danazol administration under conditions that blocked the first ovulation. Uterine weight and PGF2 alpha catabolic activity enhanced by endogenous estrogen were greatly decreased by danazol treatment at a dose that did not block the first ovulation in immature rats. When danazol (30 mg) was given s.c. once daily for 2 days to ovariectomized rats, the uterine weight and PGF2 alpha catabolic activity per uterus were clearly increased, and the compensatory increase in FSH levels as a result of castration was not influenced, although the compensatory increase in LH levels was inhibited. These results demonstrate that danazol has a direct action on the ovary and uterus, and give further support to the view put forward in our previous paper that these actions of danazol may contribute to its therapeutic effects.

A role of prostaglandin in the secretion of inhibin and oestradiol-17β in equine chorionic gonadotrophin-primed rats

The role of prostaglandins in the secretion of inhibin and oestradiol-17 beta was examined in immature female rats treated with equine chorionic gonadotrophin. Administration of prostaglandin (PG) F2 alpha to animals whose serum and ovarian levels of inhibin and oestradiol-17 beta had been suppressed by indomethacin given 24 h after equine chorionic gonadotrophin prevented the inhibition or restored the levels to normal. Initiation of PGF2 alpha replacement immediately after treatment with indomethacin was more effective. The results are consistent with the hypothesis that PGs play a regulatory role in the synthesis and secretion of inhibin and oestradiol-17 beta by the rat ovary.