Tsutomu Yaginuma

Effect of Paeoniflorin, Glycyrrhizin and Glycyrrhetic acid on Ovarian Androgen Production

We have shown that traditional herbal medicine, Shakuyaku-Kanzo-To consisted of Shakuyaku and Kanzo decreased serum testosterone levels in woman and rat. Therefore, paeoniflorin and glycyrrhizin, a main component of Shakuyaku and Kanzo, respectively, and glycyrrhetic acid, a metabolite of glycyrrhizin in vivo, were investigated for the steroid production in the rat ovary on the morning of proestrus. The homogenized tissues of one ovary were incubated in the Dulbeccos modified Eagle medium (pH 7.5) with 100 micrograms/ml of paeoniflorin, glycyrrhetic acid and glycyrrhizin and the medium only (the control) at 37 degrees C for 270 min. After the centrifugation, the concentrations of delta 4-androstenedione, testosterone and estradiol in the supernatants were determined by RIA. The production of the hormones expressed by [concentration x supernatant volume/weight of the ovary] was compared to the control. Paeoniflorin, glycyrrhetic acid and glycyrrhizin decreased significantly the testosterone production but did not change that of delta 4-androstenedione and estradiol. Testosterone/delta 4-androstenedione production ratio was lowered significantly by paeoniflorin, glycyrrhetic acid and glycyrrhizin. Estradiol/testosterone production ratio was increased significantly by glycyrrhetic acid and not changed by paeoniflorin and glycyrrhizin. These results suggest that paeoniflorin, glycyrrhetic acid and glycyrrhizin affect the conversion between delta 4-androstenedione and testosterone to inhibit testosterone synthesis and stimulate the aromatase activity to promote estradiol synthesis by the direct action on the rat proestrous ovary.

Primary pulmonary hypertension in pregnancy

Primary pulmonary hypertension (PPH) is an uncommon but serious disease. Most patients with PPH are young women and the disease is more serious and eventful in pregnant women. We have experienced a patient with PPH in pregnancy, who was delivered successfully but died suddenly on the 7th day after the delivery. We report the obstetric course and the clinical management for the delivery of the patient with PPH.

Effect of Traditional Herbal Medicine, Shakuyaku-Kanzo-To on Total and Free Serum Testosterone Levels

The effect of the traditional herbal medicine, Shakuyaku-Kanzo-To (SK), which contains Shakuyaku (S) and Kanzo (K) in equal amounts, on serum testosterone levels was investigated in androgen-sterilized rats. They were given orally SK [0, 22.5, 45, 90 and 180 mg/kg body weight (b.w.)] and S or K (0, 11.25, 22.5, 40 and 90 mg/kg b.w.) in 2 ml of water daily for 2 weeks. Dose-dependent decreases in free serum testosterone (T) levels were found in the administration of SK. Total serum T levels in the administration of SK and S decreased in a dose-dependent manner. K decreased total serum T levels slightly in 11.5 and 22.5 mg/kg doses but showed the dose-dependent increase in much higher doses, the extent of which was much less than that of the decrease in S. Serum estradiol/T (E2/T) ratios were significantly elevated in 45 to 180 mg/kg doses of SK, 90 mg/kg dose of S and 11.25 to 90 mg/kg doses of K. Serum LH and FSH levels were not changed by SK, S and K. Oophorectomized rats were similarly given SK (0, 90 and 180 mg/kg b.w.) and S or K (the half doses of SK). There were no changes in serum T, LH and FSH levels in all given doses. Thus, one of the mechanisms for SK to lower serum T levels is the direct action on the ovary to stimulate the aromatase activity, resulting in decreasing the T secretion and this is the additive effects of S and K.

Preventive effect of traditional herbal medicine, shosaiko-to, on danazol-induced hepatic damage

The incidence of the hepatic damage during treatment with danazol (D), indicated by increased serum GOT, GPT and LDH levels, has been shown to be high especially in Japan. Thus, the preventive effect of the traditional herbal medicine, shosaiko‐to (SS) was investigated in the administration of D and SS for 16 weeks (D + SS group, N = 9) and the pre‐administration of SS for about 4 weeks followed by D and SS for 16 weeks (SS → D + SS group, N = 15). The incidence of serum GOT, GPT and LDH levels of more than normal range during the administration of danazol in the D + SS group was similar to that in the previous study of the administration of D alone. But it was significantly lower in the SS → D + SS group than the D + SS group. The mean levels of serum GOT and GPT were much lower in the SS → D + SS group than the D + SS group throughout the administration of danazol and the difference was significant at 8, 10 and 12 weeks in serum GOT levels and at 4 weeks in serum GPT levels. These results indicate that the pre‐administration of SS has great efficacy in the prevention of danazol‐induced hepatic damage.

Urinary surge of human luteinizing hormone in infertile women

An improved semiquantitative immunoassay method allows human luteinizing hormone (hLH) in urine to be detected from 2.5 to 640 mIU/ml has developed. With this method, the hLH surges in every 3 h urine samples while awake were measured in 8 normal and 12 infertile women. The result was that the urinary hLH surge in infertility was insufficient regardless of the high urinary E2 value. This result may play, at least in part, an etiologic role in infertility.

Evaluation of the dopaminergic neuroendocrine control of prolactin release during labor in humans

Eight women with normal term pregnancy were i.v. administered 10 mg Metoclopramide (M), dopamine antagonist, before and during labor. Serum prolactin (PRL), TSH, GH and cortisol levels were measured at -30, 0, 30 and 60 minutes after M administration by specific radioimmunoassay. Basal serum PRL levels before labor, 287.5 +/- 28.6 ng/ml (mean +/- S.E.), significantly declined during labor to 237.0 +/- 22.4 and 216.4 +/- 22.9 ng/ml (p less than 0.05 at both) at 0 and 30 minutes before M administration, respectively. The increments in serum PRL at 30 and 60 minutes after M administration during labor (209.5 +/- 33.9 and 120.0 +/- 27.1 ng/ml, respectively) were not significantly different from those before labor (202.1 +/- 48.7 and 89.9 +/- 30.1 ng/ml, respectively), suggesting that the decline in serum PRL levels during labor is not due to the dopaminergic control. Basal serum TSH and GH levels were not significantly changed by labor and M administration either before or during labor. Serum cortisol levels tended to increase during labor, but these changes were not significant. The data suggest that the PRL releases from the pituitary during labor are not controlled by the dopaminergic mechanism.