[Urinary 17-ketogenic steroids (17-KGS) and 17-KGS fractions].
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17-Hydroxycorticosteroids↗
Biomedical subjects
Y Okatani
Publications and source records attributed to Y Okatani.
[Urinary tetrahydro-11-deoxycortisol (THS)].
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Cortodoxone↗
Effect of estrogen and simvastatin on low-density lipoprotein subclasses in hypercholesterolemic postmenopausal women.
OBJECTIVE: To identify the effects of estrogen and simvastatin, individually and in combination, on the levels of low-density lipoprotein (LDL) subclasses in postmenopausal women with type IIa hypercholesterolemia. METHODS: Fifty-five postmenopausal women with type IIa hypercholesterolemia were assigned randomly to 0.625 mg of conjugated equine estrogen (n = 20), 5 mg of simvastatin (n = 18), or both (n = 17) daily for 3 months. Cholesterol, triglyceride, and apolipoprotein B levels in the plasma and in the LDL1 (density 1.019-1.045 g/mL) and LDL2 (density 1.045-1.063 g/mL) fractions were measured before and after treatment. RESULTS: Estrogen treatment significantly reduced LDL1 cholesterol and LDL1 apolipoprotein B levels by 18.4% and 20.8%, respectively; simvastatin treatment by 21.9% and 29.2%, respectively; and combination therapy by 38.5% and 34.4%, respectively. In contrast to estrogen or simvastatin treatment, the combination therapy also significantly lowered the levels of LDL2 cholesterol by 19.5% and LDL2 apolipoprotein B by 30.5%. Posttreatment levels of total cholesterol, LDL1 cholesterol, and LDL1 apolipoprotein B were significantly lower after combination treatment than after estrogen treatment. Estrogen treatment, but not combination therapy, significantly increased total plasma triglyceride levels (103.1+/-26.0 mg/dL to 138.8+/-75.6 mg/dL, P < .01). Significantly more patients receiving combination therapy than those receiving estrogen had total and LDL cholesterol concentrations reduced to target levels. CONCLUSION: Combination therapy with estrogen and simvastatin favorably affected lipid metabolism by reducing large and small LDL particles and prevented the estrogen-induced increase in plasma triglyceride levels.
Estrogens, Conjugated (USP)↗
Effect of estrogen on melatonin synthesis in female peripubertal rats.
Our objective was to evaluate the effect of estrogen on the synthesis of melatonin in female rats during the peripubertal period. The level of melatonin and of N-acetyl serotonin (NAS) and the activity of N-acetyltransferase (NAT) and of hydroxy-indole-O-methyltransferase (HIOMT) were determined in homogenates of pineal glands from peripubertal female Sprague-Dawley rats in the mid-dark during the daily light/dark cycle between 4 and 10 weeks of age. Ovariectomy was performed and daily administration of estradiol benzoate (E2B) was initiated at 6 weeks of age. A peak in the pineal level of melatonin and NAS and in NAT activity was observed in untreated (control) rats with intact ovaries at 6 weeks. Thereafter, HIOMT activity increased and remained unchanged. Ovariectomy at week 6 led to significant increases in the level of melatonin and of NAS and in NAT activity at week 8. At week 10, NAT activity was similar to that of control animals, but melatonin and NAS levels were slightly elevated. Ovariectomy did not affect HIOMT activity. The subcutaneous injection of a low dose (0.1 microg/day) of E2B suppressed the ovariectomy-induced elevation of levels of melatonin and NAS and of NAT activity, similar to that seen in rats with intact ovaries. A higher dose of E2B (1.0 microg/day) reduced the activity of NAT and HIOMT to values significantly below the control values. Results suggest that estrogen modulates the nocturnal synthesis of melatonin by the pineal gland in peripubertal female rats. The decline in melatonin synthesis during puberty may be related to an increase in the estrogen level. The inhibitory effect of estrogen in melatonin synthesis appeared to be mediated by the modulation of NAT activity.
Acetylserotonin O-Methyltransferase↗
Effect of estrogen on melatonin synthesis in female peripubertal rats as related to adenylate cyclase activity.
To determine the mechanism for the modulatory effect of estrogen on melatonin synthesis, we evaluated the effects of estrogen on the activity of adenylate cyclase in female Sprague-Dawley rats of peripubertal age. Adenylate cyclase activity was measured in homogenates of pineal glands from rats aged 3 and 10 weeks in the mid-dark and in the mid-light. Ovariectomy was performed and a subcutaneous injection of estradiol benzoate (E2B) was administered daily starting at the age of 6 weeks. A peak in adenylate cyclase activity in the pineal gland was observed in untreated (control) rats with intact ovaries at 4 weeks. Ovariectomy at week 6 led to significant increases in the activity of adenylate cyclase at week 8. At week 10, adenylate cyclase activity resembled that of control animals. The subcutaneous injection of E2B (1.0 microg/day) suppressed the increase in adenylate cyclase activity induced by ovariectomy, similar to the level seen in control rats with intact ovaries. The changes in the mid-light activity of pineal adenylate cyclase resembled that seen at the mid-dark with the value being significantly lower than that observed in the mid-dark. Such changes in the mid-dark activity of adenylate cyclase resembled those observed with N-acetyltransferase (NAT) at the same time, as previously described. Results suggest that estrogen modulates adenylate cyclase activity in the pineal gland of peripubertal female rats. The decline in melatonin synthesis during puberty may be related to an increase in estrogen level. The inhibitory effect of estrogen on melatonin synthesis appeared to be mediated by a change in the norepinephrine-induced stimulation of pineal adenylate cyclase activity.
Adenylyl Cyclases↗
Estrogen modulates the nocturnal synthesis of melatonin in peripubertal female rats.
Our objective was to evaluate the effects of estrogen deficit and of estrogen stimulation on the synthesis of pineal melatonin in female rats during the peripubertal period. The levels of melatonin and N-acetylserotonin (NAS) and the activities of N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) were determined in homogenates of pineal glands obtained from peripubertal female Sprague-Dawley rats 4 to 12 weeks of age in the mid-dark during the daily light/dark cycle. Animals were ovariectomized at 4 weeks of age; daily administration of estradiol benzoate (E2B, 1.0 microg/d, s.c.) was initiated at 4 weeks of age. A peak in the pineal levels of melatonin and NAS and in NAT activity was observed in untreated (control) rats with intact ovaries at 6 weeks. HIOMT activity increased from Week 4 to 6 and remained unchanged thereafter. Ovariectomy at Week 4 led to significant increases in the levels of melatonin and of NAS and NAT in activity at Week 8. NAT activity Week 10 resembled that of control animals, but levels of melatonin and NAS were slightly elevated. Ovariectomy did not affect HIOMT activity. Subcutaneous injection of E2B significantly decreased the levels of melatonin and NAS and of NAT activity at Week 4, as compared with those in control rats. E2B suppressed the ovariectomy-induced elevation of levels of melatonin and NAS and of NAT activity, similar to the effect in control animals. E2B did not affect HIOMT activity. Our results suggest that estrogen modulates the nocturnal synthesis of melatonin in the pineal gland in peripubertal female rats. The effects of estrogen on melatonin synthesis appeared to be mediated by the modulation of NAT activity.
Acetylserotonin O-Methyltransferase↗
Maternal-fetal transfer of melatonin in pregnant women near term.
Our objective was to evaluate the maternal-fetal transfer of melatonin in pregnant women. Serum melatonin concentration was measured by high-performance liquid chromatography with electrochemical detection in a maternal vein and in the umbilical artery and umbilical vein at the time of birth. Blood samples were obtained from 12 women who had spontaneously delivered vaginally at night. A single oral dose of melatonin was administered to each of 33 patients who underwent a cesarean section, and, blood samples were taken at 1, 2, 3, or 4 hr after the administration of melatonin at delivery. Cesarean section was performed between 1300 and 1500 hr. The mean melatonin concentrations of melatonin in maternal peripheral venous blood and umbilical arterial and umbilical venous blood did not differ significantly, and positive correlations in the serum levels of melatonin were observed between the three sources of blood. The oral administration of 3 mg of melatonin to pregnant women led to marked increases in the serum levels of melatonin, with maximum levels observed 2 hr (21.84 +/- 2.09 ng/ml) after drug administration. Changes in serum levels of melatonin in the umbilical vein and artery resembled those found in the maternal vein. Serum melatonin concentrations did not differ significantly between the maternal vein and the umbilical veins. Serum levels of melatonin in the umbilical vein after the administration of melatonin were significantly and closely correlated with those in the maternal vein (r = 0.924, P < 0.001). These results suggest that, in humans, melatonin is transferred from the maternal to the fetal circulation both easily and rapidly. A potential for the therapeutic use of melatonin as an antioxidant exists in the patients with preeclampsia.
Adolescent↗
Effects of superoxide and peroxynitrite on vascular tension in the human umbilical artery.
BACKGROUND: While nitric oxide (NO) has been demonstrated to regulate vascular tone, superoxide (O2-) may also have an important role in regulating tension in the human fetoplacental vasculature. We therefore evaluate the effects of O2- and peroxynitrite (ONOO-) on vascular tension in isolated human umbilical arteries. METHODS: Helical sections of umbilical arteries were obtained from healthy pregnant women who were delivered between weeks 37 and 39 of gestation. Changes in maximal potassium chloride (KCl)-induced tension were measured in umbilical artery segments with intact endothelium. RESULTS: We found that hypoxanthine plus xanthine oxidase significantly potentiated vascular tension, and that this effect was suppressed by pretreatment with L(NG)-monomethyl arginine (LNMA). Pretreatment with hypoxanthine plus xanthine oxidase, however, significantly inhibited the relaxation induced by the calcium ionophore A23187. 3-morpholinosydomine (SIN-1), which releases O2- and NO simultaneously produced a significant dose-dependent relaxation of vascular tension, which pretreatment with hemoglobin did not affect SIN-1-induced relaxation. Pretreatment with methylene blue significantly attenuated, while pretreatment with superoxide dismutase (SOD) significantly potentiated this effect. CONCLUSION: These findings suggest that O2- potentiates vascular tension in human umbilical artery, in part, by suppressing NO synthesis in the endothelium. The vasorelaxation by exogenously generated ONOO suggests that this moiety has biological relevance in vasoregulation of the human umbilical artery.
Female↗
Nocturnal changes in pineal melatonin synthesis during puberty: relation to estrogen and progesterone levels in female rats.
Our objective was to evaluate the changes in melatonin synthesis during the peripubertal period in the female rat and to determine the effects of ovarian steroid hormones on melatonin synthesis. Pineal levels of tryptophan, 5-hydroxytryptamine (5-HT), melatonin and norepinephrine were determined in female Sprague Dawley rats (between 2 and 12 weeks of age) in the mid-dark during the daily light/dark cycle. Melatonin levels increased with age, parallel to pineal growth, until 6 weeks of age, when the vaginal opening was found in 66.7% of rats, and significantly decreased until 8 weeks of age, when the vaginal opening was found in all rats. Norepinephrine began to increase earlier and reached a mature level at 4 weeks of age. Treatments with bilateral ovariectomy at 4, 6, and 8 weeks of age resulted in significant increases in melatonin and 5-HT levels, and significant decrease in tryptophan level at 2 weeks after ovariectomy. Treatments with ovariectomy at 6 weeks of age produced a consistent increase in 5-HT level and a consistent decrease in tryptophan level until 6 weeks after ovariectomy. However, melatonin levels increased until 2 weeks after ovariectomy, then decreased and reached a control level at 6 weeks after ovariectomy. Subcutaneous implantation of estradiol-17 beta capsule and daily subcutaneous injection of estradiol benzoate (E2B) (1.0 microgram, 20 micrograms) for two weeks in the rats ovariectomized at 4, 6, and 8 weeks of age resulted in significant decreases in melatonin and 5-HT levels and a significant increase in tryptophan level at 2 weeks after ovariectomy. A smaller dose of E2B (0.1 microgram) produced the same effects in the rats ovariectomized at 4, but not at 6 and 8 weeks of age. Administration of progesterone (200 micrograms/day) for 2 weeks did not produce any significant changes in melatonin, 5-HT, and tryptophan levels. Norepinephrine levels were not changed by any of the above treatments. These results suggest that estrogen, but not progesterone, can modulate nocturnal pineal melatonin synthesis in peripubertal female rats, and that the decline in the melatonin synthetic activity during the pubertal period might be related to the increasing levels of endogenous estrogen, which is secreted from the maturing ovary. The sites of action of the inhibitory effect of estrogen on the pineal melatonin synthesis may be multiple.
Age Factors↗
Melatonin inhibits vasospastic action of hydrogen peroxide in human umbilical artery.
We evaluated the antioxidant property of melatonin as it relates to the vasospastic effect of hydrogen peroxide (H2O2) on the human umbilical artery. Helical sections of umbilical arteries were obtained from healthy pregnant women who were delivered between weeks 37 and 39 of gestation. Changes in maximal potassium chloride (KCl)-induced tension were measured in arterial segments with intact endothelium. Segments were treated with H2O2 alone, or were pretreated either with an H2O2 scavenger (catalase, 2000 i.u.), a hydroxyl radical scavenger (mannitol, 10(-2) M), a nitric oxide-synthesis inhibitor (L-NG-monomethyl arginine, LNMA, 2 x 10(-4) M), or melatonin (10(-6) M to 10(-4) M). The effect of H2O2 (10(-4) M) on the relaxation induced by the calcium ionophore A23187 was also determined in arterial segments, with or without pretreatment with melatonin (10(-6) M, 10(-4) M). H2O2 (10(-6) M to 10(-4) M) potentiated vascular tension in a concentration-dependent manner (P < 0.0001). Pretreatment with LNMA significantly suppressed the vasospastic effect of H2O2 (P < 0.0001). Pretreatment with either catalase or mannitol significantly reduced the vasospastic effect of H2O2 (P < 0.005, P < 0.002, respectively). Melatonin also significantly reduced the vasospastic effect of H2O2 in a concentration-dependent manner (H2O2 10(-6) M, P < 0.0001 : H2O2 10(-5) M, P < 0.0001 : H2O2 10(-4) M, P < 0.00001). Pretreatment with H2O2 significantly inhibited the relaxation induced by the calcium ionophore A23187 (P < 0.005). Treatment with melatonin prior to exposure to H2O2 significantly restored the relaxation induced by A23187 (P < 0.005). Results suggest that H2O2 potentiates vascular tension in the human umbilical artery, perhaps by suppressing the endothelial synthesis of nitric oxide. Melatonin significantly suppressed the vasospastic effect of H2O2, possibly due to its ability to scavenge the hydroxyl radical.
Antioxidants↗
Melatonin suppresses vasospastic effect of hydrogen peroxide in human umbilical artery: relation to calcium influx.
We evaluated the hydroxyl radical scavenging effect of melatonin on the vasospastic action induced by hydrogen peroxide in human umbilical artery. Helical sections were made of umbilical arteries obtained from healthy pregnant women who were delivered between 37 and 39 weeks of gestation. Changes in maximal potassium chloride (KCl, 10[-2] M)-induced tension were measured in umbilical artery segments with intact endothelium. Segments were treated with H(2)O(2) (10[-9] M to 10[-7] M) only, or were pretreated with an H(2)O(2) scavenger (catalase, 2,000 IU), a hydroxyl radical scavenger (mannitol, 10[-2] M), or melatonin (10[-8] M to 10[-6] M). The effect of H(2)O(2) on the response of the segments of umbilical artery to external calcium was determined. Changes in KCl-induced contraction were also determined in segments pretreated with an inhibition of intracellular calcium release (ryanodine, 10[-4] M) prior to exposure to H(2)O(2). Pretreating the segments of umbilical arteries with H(2)O(2) (10[-8] M, 10[-7] M) significantly potentiated the maximal contraction induced by KCl (P < 0.0001, P < 0.03, respectively). Pretreatment with either catalase or mannitol significantly reduced the vasospastic effect of H(2)O(2) (10[-8] M) (P < 0.0001, P < 0.0001, respectively). Melatonin also significantly reduced the vasospastic effect of H(2)O(2) (10[-8] M), in a concentration-dependent manner (P < 0.0001). H(2)O(2) (10[-8] M) significantly increased the contractile response to external calcium. Melatonin pretreatment significantly suppressed the contractile response to external calcium. Treatment with ryanodine prior to exposure to H(2)O(2) did not affect KCl-induced contraction. Results suggest that H(2)O(2) potentiates the KCl-induced maximal contraction of the human umbilical artery, perhaps by increasing calcium influx via activation of the voltage-dependent calcium channel. Melatonin significantly suppresses the vasospastic effect of H(2)O(2), probably due to its scavenging of the hydroxyl radical.
Adult↗
Effect of nitric oxide, prostacyclin, and thromboxane on the vasospastic action of hydrogen peroxide on human umbilical artery.
BACKGROUND: The effect of hydrogen peroxide (H2O2) on vascular tone in the human umbilical artery was investigated to determine the mechanism of vasospasm in preeclampsia. METHODS: Helical sections of the umbilical artery were obtained from healthy pregnant women who delivered between the 37th and 39th week of gestation. Changes in the maximal tension induced by prostaglandin F2 alpha (PG F2 alpha) were measured (isometric mechanical activity). Segments were treated with H2O2 alone or H2O2 after pretreatment with a scavenger of hydroxyl radicals (mannitol), an inhibitor of thromboxane synthesis (sodium ozagrel), and an inhibitor of nitric oxide synthesis (L-NG-monomethyl arginine, LNMA), or an inhibitor of prostacyclin synthesis (tranylcypromine, TCP). RESULTS: Vascular tension was potentiated by H2O2 in a concentration-dependent manner. Pretreatment with mannitol significantly suppressed the vasospastic effect of H2O2. Removal of the endothelium decreased the vascular tension induced by H2O2. Treatment with TCP and LNMA potentiated the vascular tension. Pretreatment with TCP and LNMA reduced the vasospastic action of H2O2, whereas pretreatment with sodium ozagrel did not. CONCLUSION: Vascular tension in human umbilical arteries was potentiated by H2O2, and may be mediated by a suppression of the activity of nitric oxide or of prostacyclin. A direct action of H2O2 on vascular smooth muscle may also be involved.
Epoprostenol↗
Vasospastic action of hydrogen peroxide in human umbilical artery: relation to protein kinase C and calcium influx.
BACKGROUND: We have demonstrated that hydrogen peroxide (H2O2) potentiated vascular tension in human umbilical artery, perhaps by suppressing the synthesis of nitric oxide and prostacyclin. This study was conducted to evaluate whether the activation of protein kinase C (PKC) or voltage-dependent calcium channel mediated the vasospastic effect of H2O2. METHODS: Helical sections of the umbilical artery were obtained from healthy pregnant women who delivered between 37th and 39th week of gestation. Changes in the maximal tension induced by prostaglandin F2 alpha (9 x 10(-7) M) were measured (isometric mechanical activity). Segments were treated with H2O2 (10(-6)-10(-4) M) alone or H2O2 after pretreatment with a scavenger of hydroxyl radicals (mannitol, 10(-2) M), an inhibitor of PKC (H-7, 6 x 10(-7) M). Effect of an activator of PKC (12-tetradecanoyl phorbol-13 acetate, TPA, 10(-6) M) on PG F2 alpha-induced tension was determined. Effects of H2O2 (10(-5) M) on the response of umbilical artery segments to an external calcium (10(-6)-10(-3) M) were determined. RESULTS: Vascular tension was potentiated by H2O2 in a concentration-dependent manner. Pretreatment with mannitol significantly suppressed the vasospastic effect of H2O2. Pretreatment with H-7 did not alter the response to H2O2. TPA did not produce a significant change in PG F2 alpha-induced tension. Pretreatment with H2O2 (10(-5) M) did not alter the contractile response to external calcium. CONCLUSION: H2O2 potentiated vascular tension in human umbilical arteries, a process that is independent of PKC and the voltage-dependent calcium channel. The vasospastic effect of H2O2 may be mediated by a suppression of the activity of nitric oxide and prostacyclin.
Analysis of Variance↗
Relaxant effect of nitric oxide and prostacyclin on serotonin-induced vasocontraction of human umbilical artery.
BACKGROUND: We investigated the effect of nitric oxide and prostacyclin, which are endothelium-derived vasodilators, on serotonin (5-HT)-induced vasocontraction, and 5-HT1-serotoninergic receptor mediated relaxation in the human umbilical artery. METHODS: Serotonin-stimulated vasocontraction was measured in umbilical artery segments treated with and without 1) L-arginine (10(-4) M approximately 10(-2) M), a precursor of nitric oxide synthesis; 2) methylene blue (10(-5) M) and L-NG-monomethyl arginine (LNMA, 2 X 1O(-4) M), which are specific inhibitors of nitric oxide action and nitric oxide synthesis, respectively; and 3) tranylcypromine (2 X 10(-6) M, 2 X 10(-5) M), an inhibitor of prostacyclin synthesis. 4) Vessels were pretreated with M1, an inhibitor of 5-HT2 serotoninergic receptors, and then prostaglandin F2 alpha (9.O X 1O(-7) M). Finally, we measured the 5-HT1, receptor-mediated relaxation induced by 5-HT. RESULTS: Treatment with L-arginine significantly inhibits 5-HT-induced contraction in a dose-dependent manner. Treatment with methylene blue and LNMA significantly potentiated 5-HT-induced contraction. Tranylcypromine caused no significant changes in 5-HT-induced vasocontraction. 5-HT1 serotoninetic receptor-mediated relaxation was found at higher concentrations of 5-HT (greater than 4.94 X 10(-5) M). CONCLUSIONS: Our results suggest that nitric oxide may exert a strong relaxant effect on 5-HT-induced vasocontraction compared with prostacyclin in human umbilical artery.
Arginine↗
Potentiating effect of hydrogen peroxide on the serotonin-induced vasocontraction in human umbilical artery.
BACKGROUND: Our objective was to investigate the role of hydrogen peroxide in the vasocontraction induced in the human umbilical artery by serotonin. METHODS: Umbilical arteries collected from healthy women at term were cut helically and suspended in an organ bath to record isometric mechanical activity. In Study I, we measured the concentration-contraction response to serotonin with or without pretreatment with hydrogen peroxide (0.01-10 microM). In Study 2, vessels were pre-incubated with L-arginine (0.1-10mM), or with hydrogen peroxide (10 mM) and L-arginine (1 mM), then serotonin was added cumulatively. In Study 3, vessels were suspended in a calcium-free solution containing potassium chloride 20 mM, and a cumulative concentration-response curve to calcium chloride (10(-5)-10(-3) M) was constructed for vessels pretreated with hydrogen peroxide (10 microM). In Study 4, vessels were pre-treated with M1, an inhibitor of 5-HT2 serotoninergic receptors, and hydrogen peroxide (10 microM), and then prostaglandin F2 alpha (9.0 x 10(-7) M). Finally, we measured the 5-HT1 receptor-mediated relaxation induced by serotonin. RESULTS: Hydrogen peroxide (1 or 10 microM) significantly potentiated the contractile response to serotonin (p < 0.04, p < 0.005). L-arginine (1 or 10 mM) significantly reduced the contractile response to serotonin (p < 0.02, p < 0.0002). Pretreatment with L-arginine significantly suppressed the potentiating effect of hydrogen peroxide on the serotonin-induced contraction. The sensitivity of the arteries to calcium chloride in the presence of hydrogen peroxide did not differ from that in the control group. Pretreatment with hydrogen peroxide significantly reduced the 5-HT1 serotoninergic receptor-mediated relaxation at higher concentrations of serotonin (1.23 x 10(-4) M, 2.47 x 10(-4) M, 2.47 x 10(-4) M). CONCLUSION: Hydrogen peroxide potentiated the umbilical artery contraction induced by serotonin. This action may be mediated by suppression of endogenous nitric oxide activity.
Arginine↗
Amplifying effect of endothelin-1 on serotonin-induced vasoconstriction of human umbilical artery.
OBJECTIVE: The purpose of this study was to evaluate the role of endothelin-1 in serotonin-induced vasoconstriction in human umbilical artery. STUDY DESIGN: Umbilical arteries collected from 41 normal subjects at term were cut helically and suspended in an organ bath for recording isometric mechanical activity. In study 1 we measured the concentration-contraction response to serotonin or endothelin-1 according to a cumulative concentration schedule. In study 2 vessels were preincubated with a subthreshold concentration of endothelin-1 (100, 250, or 500 pg/ml), and then serotonin was added cumulatively. In study 3 vessels were preincubated with H-7 (3 x 10(-6) mol/L), an inhibitor of protein kinase C, or with 12-tetradecanoylphorbol-13 acetate (10(-9) to 10(-7) mol/L), an activator of protein kinase C; then serotonin was added cumulatively. In study 4 vessels were suspended in a calcium-free solution containing 2 mmol/L ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid and 60 mmol/L potassium chloride, and then a cumulative concentration-response curve to calcium chloride (10(-7) to 10(-3) mol/L) was constructed for vessels pretreated with endothelin-1, 500 pg/ml or 5 ng/ml. RESULTS: The threshold concentrations of serotonin and endothelin-1 were 5 and 1 ng/ml, respectively. A subthreshold concentration of endothelin-1 (250 or 500 pg/ml) potentiated significantly the concentration response to serotonin (p < 0.084, p < 0.009, by analysis of variance). Pretreatment with H-7 significantly suppressed the amplifying effect of endothelin-1 on serotonin-induced contraction. Treatment with 12-tetradecanoylphorbol-13 acetate (10(-7) or 10(-8) mol/L) significantly potentiated the contractile response to serotonin (p < 0.0003, p < 0.015). The sensitivity of the arterial segments to calcium chloride in the presence of a subthreshold concentration of endothelin-1 did not differ from that in the control group. CONCLUSION: Endothelin-1 at a subthreshold concentration amplified the smooth muscle contraction induced by serotonin. The mechanism of action may be mediated by activation of intracellular protein kinase C.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Enhanced nocturnal melatonin secretion in women with functional secondary amenorrhea: relationship to opioid system and endogenous estrogen levels.
The purpose of this study was to evaluate the role of the opioid system and the estrogen environment in the nocturnal secretion of melatonin in women with secondary amenorrhea (SA). Nocturnal melatonin concentrations in patients with SA were significantly higher than in normal women (p < 0.01 vs. women with normal menstrual cycles). There were significant negative correlations between cumulative melatonin levels (between 8 p.m. and 8 a.m.) and serum estradiol-17 beta (r = -0.561, p < 0.01) and between peak serum melatonin values and serum estradiol-17 beta concentrations (r = -0.608, p < 0.01) in SA. Intravenous administration of a conjugated estrogen (Premarin 20 mg) significantly suppressed nocturnal melatonin secretion (p < 0.05), but a continuous intravenous infusion of naloxone (1.6 mg/h from 8 p.m. to 6 a.m.), an opiate antagonist, did not affect nocturnal melatonin secretion in SA. Our findings suggest that elevated nocturnal melatonin secretion may be related to low estrogen levels, but that it is not mediated by the opioid system.
Adolescent↗
[Urinary 17-ketosteroids (17-KS) and 17-KS fractions].
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17-Ketosteroids↗