Endothelin induces DNA polymerase alpha activity in ovaries of hypophysectomized estrogen-treated immature rats.
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Biomedical subjects
Publications and source records attributed to S Usuki.
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The possible direct involvement of endothelin (ET) in preovulatory follicular steroidogenesis was investigated in vitro. Follicular development in immature rats was induced by pregnant mare's serum gonadotropin (PMS). Twenty-four and 48 h after PMS injection, ovarian follicles were incubated in vitro with or without 4 x 10(-11) to 4 x 10(-5) M endothelin-1 (ET-1) or endothelin-3 (ET-3) for 2 h, or perifused in vitro with 4 x 10(-7) M of ET-1 or ET-3 for 3 h. In the incubation study, ET-1 and ET-3 significantly stimulated progesterone, testosterone, and 17 beta-estradiol production by follicles 24 and 48 h after PMS injection. Progesterone, testosterone, and 17 beta-estradiol were increased in a dose-dependent manner by 4 x 10(-11) to 4 x 10(-6) M ET-1 or ET-3; in the case of ET-3, this increase occurred only at 24 h after PMS injection. In addition, ET-1 stimulated ovarian steroid production more effectively than ET-3. In addition to their effects on ovarian steroidogenesis, both ET-1 and ET-3 increased tissue cyclic adenosine-3',5'-monophosphate (cyclic AMP) production. The steroidogenic effect of ET-1 or ET-3 was most pronounced by follicles 48 h after PMS injection. In the perifusion experiment, ET-1 and ET-3 also stimulated progesterone, testosterone, and 17 beta-estradiol secretion. These indicate the involvement of ET-1 or ET-3 in the regulation of ovarian differentiation by stimulating steroidogenesis, at least partially through the mediation of cyclic AMP.
Endothelin-1 (ET-1) may be important in regulating vascular tone in humans. To understand the role of ET-1 during pregnancy, we measured the concentrations of plasma immunoreactive ET-1 in normal, toxemic (pre-eclamptic or eclamptic), and other complicated pregnancies. There were no significant differences between ET-1 concentrations in normal pregnancy and those in toxemic pregnancy, except in one case with IgA nephropathy and severe toxemia. There also was no significant difference between the ET-1 concentrations in pure toxemia of pregnancy compared with superimposed toxemia of pregnancy. Furthermore, there was no correlation between ET-1 concentrations, blood pressure, or renal function during toxemic pregnancy. Similarly, there were no significant differences between ET-1 plasma levels in normal pregnancies and other complicated pregnancies except for two cases in which much blood was lost due to uterine atony and abruptio placenta. Thus, plasma ET-1 concentrations showed no significant relationship to blood pressure or renal function during normal or toxemic pregnancy, and were not related to the type (pure or superimposed type), grade, or severity of toxemic pregnancy.
Twenty-seven-day old female rats received 20 IU PMS and 56 hours later, 40 IU hCG. Seven days after hCG treatment, the resected ovaries were incubated in vitro with herbal components of Tokishakuyakusan (TS). Mixture of hoelen + peony root + alisma rhizone + Japanese angelica root or hoelen + Japanese angelica root or Japanese angelica root + cnidium rhizome significantly increased progesterone secretion, and these levels tended to exceed the level by TS alone. These results suggest an exquisitely blended effect of herbal components of TS on progesterone secretion by corpora lutea.
The effect of herbal components of Tokishakuyakusan on somatomedin C/insulin-like growth factor I (IGF-1) level in medium from rat corpora lutea incubated in vitro was examined. Hoelen + poeny root + Japanese angelica root, hoelen + peony root, hoelen + Japanese angelica root or peony root + Japanese angelica root decreased the IGF-1 level. The data suggest that constituent herbal components of Tokishakuyakusan regulate the IGF-1 level by rat corpora lutea.
Ovarian follicles, removed from 10-week old rats at 1630 hours diestrus-2, 1100 and 2300 hours proestrus, were incubated for 120 minutes with various doses of Hachimijiogan (HJ), Tokishakuyakusan (TS), Keishibukuryogan (KB), Ninjinto (NT) and Unkeito (UT). The estradiol-17 beta (E2) and progesterone concentrations in the incubation medium were measured. The concentrations of E2 were significantly decreased with TS and KB by growing follicles and with HJ, TS and KB by preovulatory follicles before a LH surge. In contrast, the levels of progesterone were significantly increased with HJ, TS, KB and UT by preovulatory follicles before a LH surge. These results suggest that HJ, TS, KB or UT stimulates preovulatory follicles before a LH surge to secrete progesterone, but TS or KB suppresses E2 secretion by growing preovulatory follicles before a LH surge.
A hyperprolactinemic infertile woman with a pituitary microadenoma, who was resistant to bromocriptine as a method of bringing on pregnancy, succeeded in having a normal pregnancy and delivery with Hachimi-jio-gan treatment. This paper reports that the patient did not succeed in pregnancy in spite of 16 months of bromocriptine treatment, though her prolactin level gradually decreased and continued to be between 40-60 ng/ml with Hachimi-jio-gan treatment. Although the level of prolactin of the patient did not normalize, she, nevertheless, succeeded in having a normal pregnancy and delivery.
To examine the possible effects of Tokishakuyakusan (TS) on steroidogenesis by preovulatory follicles at the cell level, the expressed granulosa cells and remaining portion of follicles from pregnant mare's serum gonadotropin (PMS)-treated immature rats were incubated in vitro with increasing concentrations of TS for 3 h. TS significantly stimulated progesterone and estradiol-17 b production, with a predominant stimulation of progesterone, by the expressed granulosa cells, while testosterone production was not stimulated. In the remaining portion of the follicle, TS also significantly stimulated progesterone, testosterone and estradiol-17 b production. Similar to the effect produced by granulosa cells, the stimulatory effect of TS was stronger on progesterone than on testosterone and estradiol-17 b production. These results suggest that TS has a potent, direct stimulatory effect on steroidogenesis, especially progesterone production, by constituent tissue compartments of rat preovulatory follicles in vitro.
The effect of Tokishakuyakusan (TS) on the corpus luteum function in pseudopregnant rats was examined in vivo. On day 4 of pseudopregnancy (PSP), induced by cervical stimulation, TS (20 micrograms) stimulated the progesterone secretion rate (PSR) in the ovarian venous plasma. There was also a significant increase in the rate of progesterone to 20 alpha-OH-progesterone. However, on day 8 of PSP, there was no apparent change in PSR in the ovarian venous plasma after the administration of TS. These data suggest that the sensitivity to TS of the corpus luteum varies according to its age.
Effect of Hachimijiogan (HJ) on dopamine (DA), serotonin (5-HT) and vasoactive intestinal peptide (VIP) was examined in plasma and hypothalamic tissue of sulpiride-induced hyperprolactinemic rats (SHR). Similar to bromocriptine (BR), HJ, in combination with sulpiride, suppressed plasma prolactin levels raised by sulpiride alone. Furthermore, HJ, together with sulpiride, increased plasma DA levels decreased by sulpiride alone, while 5-HT in plasma was increased by sulpiride and HJ, individually or in combination. However, plasma VIP levels were under detection limits on some occasions after HJ treatment. Successively, DA, 5-HT and VIP levels in the hypothalamus were determined. Similar to the effect caused by BR, DA and 5-HT levels in hypothalamic tissue reduced by sulpiride alone were also significantly increased by HJ together with sulpiride, while VIP levels were sometimes under detection levels with or without HJ. These results suggest that HJ stimulates the hypothalamus to increase DA and 5-HT in SHR, providing evidence for the clinical efficiency of HJ in combating hyperprolactinemia. The effect of HJ on VIP in plasma or hypothalamic tissue is, however, questionable.
The presence of endothelin-1 (ET) and effect of Tokishakuyakusan (TS) on ET in rat corpora lutea (CL) was investigated in superovulated ovaries, induced with pregnant mare's serum gonadotropin and human chorionic gonadotropin. A high concentration of ET was found in the CL. The level of ET was significantly lower in the CL from TS-treated rats than that in TS-untreated rats (402.68 versus 575.60 pg/g wet weight, p less than 0.05). In contrast, the ET levels in plasma were by far lower than those in CL. These data indicate an inhibitory effect of TS on ET, an intraovarian peptide, production or accumulation in the CL.
A 65-year-old woman with diabetes mellitus (DM) and suffering a cataract in the left eye, that was resistant to Western medical treatment, was treated with goshajinkigan (GJ), a herbal medicinal drug, in combination with eye drops. This treatment remarkably improved the visual disturbance due to the senile cataract. Ten days after commencement of the GJ treatment, her visual acuity did not deteriorate any further. There was also no further deterioration of DM condition. These results suggest that GJ may be valuable in the treatment of diabetic women with cataracts.
The hearts of 28 necropsy cases with DCM and 10 control cases were analysed to elucidate the role of myocarditis and fibrosis in dilated cardiomyopathy (DCM). The extent of fibrosis and myocyte diameter were measured in the transverse sections of the left ventricle. The degree and pattern of fibrosis varied widely from case to case. The DCM cases were then classified into 3 groups: 1) Group Ia, 8 cases with mild diffuse fibrosis; 2) Group Ib, 9 cases with severe diffuse fibrosis and 3) Group II, 11 cases with segmental fibrosis. Myocardial fibrosis and hypertrophy were significantly more prominent in Groups Ib and II than in the control group (p less than 0.01), but no differences were observed between Group Ia and the control group. Thus, it is reasonable to attribute the chronic CHF and LV dilatation in Groups Ib and II to the extensive myocardial fibrosis. In contrast, it is not reasonable to attribute the chronic CHF and LV dilatation in Group Ia to myocardial fibrosis. Focal lymphoid cell infiltration was graded to assess inflammatory changes. Group II showed more prominent inflammatory changes than the other 2 groups (p less than 0.05). Thus, it is possible that myocarditis is an etiologic factor for DCM with a segmental pattern of fibrosis.
The effects of verapamil on the diastolic function and regional asynchrony of the left ventricle were echocardiographically investigated in 37 patients with hypertrophic non-obstructive cardiomyopathy (HCM). Before and 20 min after the intravenous administration of verapamil (0.1 mg/kg), blood pressure (BP), heart rate (HR), transmitral pulsed Doppler indices (R, A, A/R), M-mode echo indices (Dd, Ds, %FS) and the echo-phonocardiographic index (isovolumic relaxation time; IRT) were measured. We also measured the rapid extension times of the posterior walls at the chordae and papillary muscle level [Tc(pw), Tp(pw)] as the indices of regional diastolic function, and their difference [Tp-c(pw)] was used as the index of diastolic asynchrony. Before verapamil administration, the HCM patients had significantly larger A, A/R, IRT and Tp-c(pw) and smaller R than did 20 healthy controls, but showed no significant differences in HR, BP, Dd, Ds and %FS. After verapamil injection, R increased and A, A/R, IRT, Tp-c(pw) decreased significantly without any changes in BP and HR. The increment of R (delta R) correlated significantly with the decrement of Tp-c(pw) (r = -0.66, p less than 0.001). According to the value of delta R/R, 37 patients with HCM were categorized in 2 groups (19 responders with delta R/R greater than or equal to 10% and 18 non-responders with delta R/R less than 10%). The responders had smaller R and larger A/R, IRT and Tp-c(pw) before verapamil administration than did the non-responders. Verapamil increased R, Dd, Ds and decreased A, A/R and Tp-c(pw) in the responders, but not in the non-responders. These results suggested that verapamil might improve left ventricular diastolic function in HCM patients through the improvement of left ventricular diastolic asynchrony.
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The effect of Tokishakuyakusan (TS) or Keishibukuryogan (KB) on endothelin-1 (ET-1), a newly identified peptide, in plasma and amniotic fluid from TS- or KB-treated women or normal pregnant women following TS or KB treatment was studied during the menstrual cycle, gestation, delivery and the post-partum period. ET-1 levels during and/or after TS or KB treatment had no significant changes when compared with those in TS- or KB-untreated women. These results suggest that TS or KB has no effects on the ET-1 level during the menstrual cycle, gestation and the post-partum period.
The effect of Tokishakuyakusan (TS) and Keishibukuryogan (KB) on estradiol-17 beta, progesterone and testosterone in serum and ovarian tissue from PMS-treated immature rats was examined in vivo. The in vivo intravenous administration of 20 micrograms of TS or KB increased the concentrations of estradiol-17 beta, progesterone and testosterone. These results suggest that TS and KB stimulate in vivo the production of estradiol-17 beta, progesterone and testosterone by preovulatory follicles, and that TS stimulation is more effective than KB.