Effects of Tokishakuyakusan on the ovary in hypophysectomized rats

The prescription Tokishakuyakusan (TS; Dang-Gui-Shao-Yao-San in Chinese) is widely used in traditional Chinese medicine. Since delay of ovarian follicle maturation and fall of bone density are known in hypophysectomized (HPX) rats, we investigated the effects of TS on ovaries in HPX rats. Although TS did not recover the ovary weight decreased by hypophysectomy, it recovered the uterine weight. Two weeks after hypophysectomy, the expression of steroidogenic acute regulatory protein (StAR) mRNA was decreased, but recovered by administration of TS. On the other hand, the expression of pituitary adenylate-cyclase activating polypeptide receptor type I (PAC₁) and progesterone receptor (PR) mRNA was increased, but reduced by administration of TS. However, the expression of estrogen receptor α (ERα) mRNA did not synchronize with PAC₁ mRNA and PR mRNA expression. Moreover, TS was demonstrated to promote the follicle maturation by histrogical analysis, and to decrease significantly the urinary deoxypyridinoline (DPD) level. These findings suggest that TS promotes the maturation of follicles and suppresses the bone metabolism associated with pituitary hormones.