Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00691 (EE2)
 7,802 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of ethinyl estradiol (EE2) and dexamethasone (Dex) upon plasma renin substrate (PRS) was studied in rats in relation to sexual maturation and pituitary function. Normal adult rats had large increases in PRS when given either EE2 or Dex. Prepubescent (25-day-old) rats also had a substantial increase in PRS following Dex, but no increase in PRS after EE2. In adult rats, hypophysectomy prevented the rise in PRS due to EE2 but did not prevent the increase in PRS due to Dex. Hepatic estrogen and glucocorticoid receptors were measured in immature and adult rats. Immature rats had markedly reduced concentration of hepatic estrogen receptors (16%), compared with adults. In contrast, glucocorticoid receptor concentration was not significantly different between immature and adult rats. The results indicate that the effect of estrogens and glucocorticoids upon PRS are mediated by pathways that are separable at the hormone receptor level.
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PMID:Hormonal control of plasma renin substrate; (angiotensinogen). 90 71

A 53-year-old normotensive, normokalemic female presented with a 6-month history of virilization. Estradiol, LH, FSH, urinary-free cortisol, and DHEA-S levels were normal. Pelvic ultrasound and computerized tomography were also within normal limits. Her serum testosterone (551 ng/dl; nl, 20-70) and plasma prorenin (124 ng AI/ml/hr; nl, less than 50) levels were elevated. At surgery, a lipoid/steroid cell tumor of the right ovary was removed. Postoperative testosterone and prorenin levels were normal. Ovarian tumor cells, in culture, produced large amounts of prorenin. Immunohistochemistry localized prorenin and/or renin to tumor cells. Determining plasma prorenin levels may be a useful adjunct in diagnosing or following patients with nonepithelial ovarian tumors. A larger clinical study of prorenin levels in patients with such tumors is needed.
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PMID:Secretion of prorenin by a virilizing ovarian tumor. 131 55

Estradiol-17 beta (E2 beta) produces uterine and systemic vasodilation in nonpregnant ewes without altering mean arterial pressure (MAP). Mechanisms responsible for maintaining MAP and thus uterine blood flow (UBF) may include activation of the renin-angiotensin and/or adrenergic systems. We therefore investigated the effects of systemic blockade of angiotensin II (ANG II) and/or alpha-adrenergic receptors in nonpregnant, castrated ewes, using saralasin (Sar) and/or phentolamine (Phen) in the presence or absence of intravenous E2 beta (1.0 microgram/kg). In nonestrogenized ewes neither antagonist alone had substantial cardiovascular effects; however, Sar + Phen decreased systemic vascular resistance (SVR) 20 +/- 7.4% (SE) and increased heart rate (HR) 50 +/- 19% (P < 0.01); MAP and UBF were unaffected. Following E2 beta treatment SVR fell 17 +/- 2.4% (P < 0.01), UBF increased more than fourfold, and MAP was unchanged. Compared with E2 beta alone, Phen + E2 beta decreased SVR 42 +/- 4.7%, and MAP fell 11 +/- 1.8% (P < 0.05) despite 40-50% increases in HR and cardiac output (P < 0.05). Responses to Sar + E2 beta were similar to E2 beta alone, except for a fall in MAP, whereas responses to Sar + Phen + E2 beta resembled those of Phen + E2 beta. E2 beta-induced uterine vasodilation was unaltered by Sar and/or Phen. During E2 beta-induced vasodilation, MAP is maintained by enhanced activation of the alpha-adrenergic and renin-angiotensin systems; however, uterine vascular responses to E2 beta are independent of both systems and perfusion pressure.
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PMID:Role of angiotensin II and alpha-adrenergic receptors during estrogen-induced vasodilation in ewes. 133 96

One reliable, controlled and convenient method of delivering parenteral estrogen replacement therapy is by means of a transdermal patch known as the Estraderm Transdermal System, which contains a 17-beta estradiol formulation. The primary side effect appears to be a localized skin irritation in about 15 percent of the women using this route. Most women find this irritation annoying but not enough to necessitate stopping therapy. Studies indicate that the patch provides amelioration of climacteric symptoms that is comparable to the oral estrogens. Preliminary research shows that parenteral estrogen is as effective as oral estrogen in decreasing the risk of osteoporosis. No adverse changes in lipid-lipoprotein levels have been found. A recent Swedish study found an increased relative risk of breast cancer with estradiol and with combined estrogen-progestin use for postmenopausal therapy. Thus, more research on the long-term hormonal replacement effects of the patch is indicated. One advantage of the transdermal delivery system is a first bypass of the liver, thus decreasing the possible risk of renin substrate elevation and the potential increase in blood pressure associated with oral estrogen therapy.
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PMID:Estrogen replacement therapy and the estraderm transdermal system. 234 64

Female Sprague-Dawley rats were injected s.c. with ethynyloestradiol (EE2, 0.2 microgram/day) and levonorgestrel (NG, 2.0 micrograms/day) separately and in combination (EE2/NG). Binding of [3H]rauwolscine (alpha 2-adrenoceptor specific) and [3H]prazosin (alpha 1-adrenoceptor specific) was examined in crude membrane suspensions prepared from whole rat kidney after 3, 6 and 12 weeks of steroid administration. Receptor affinity was high for both ligands (KD, equilibrium dissociation constant [3H]rauwolscine, congruent to 2.0 nM; [3H]prazosin, congruent to 0.2 nM) and was not altered in rats chronically treated with steroid contraceptives. The Bmax (maximum density of binding sites) for [3H]prazosin binding was not altered, indicating no change in the number of renal alpha 1-adrenoceptors. NG administered alone did not affect the numbers of alpha 1- or alpha 2-adrenoceptors. Catechol metabolites of endogenous oestrogens did not displace the binding of either radioligand, suggesting that these metabolites do not directly interact with renal alpha-adrenoceptors. However, after 12 weeks treatment, the number of [3H]rauwolscine binding sites was reduced in both EE2 (Bmax, 133 +/- 7 fmol/mg protein)- and combined EE2/NG (135 +/- 11 fmol/mg protein)-treated rats, compared to controls (162 +/- 9 fmol/mg protein). Since renal alpha 2-adrenoceptors inhibit renin release, this reduction in alpha 2-adrenoceptor number may contribute to increased renin levels associated with oestrogen-induced hypertension.
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PMID:Chronic steroid contraceptive treatment decreases renal alpha-adrenoceptor levels in the rat. 302 4

The present studies were designed to test the hypothesis that changes in angiotensin II (ANG II) receptors might modulate the altered target tissue responsiveness accompanying estradiol administration. Estradiol was infused continuously in oophorectomized female rats by employing minipumps to achieve plasma estradiol levels and simulating pregnancy levels in the rat. Aldosterone was also infused in control and experimental animals to avoid estrogen-induced changes in renin and ANG II. ANG II binding constants were determined in radioreceptor assays. Estradiol increased binding site concentration in adrenal glomerulosa by 76% and decreased binding sites of uterine myometrium and glomeruli by 45 and 24%, respectively. There was an accompanying increase in the affinity of ANG II binding to adrenal glomerulosa and uterine myometrium. Because estrogen is a potent stimulus of prolactin release from the pituitary of rodents, studies were also designed to test the hypothesis that prolactin may mediate some or all of the estrogen-induced effects observed. Hypophysectomy abolished estradiol stimulation of prolactin release and most ANG II receptor changes. The only effect that persisted was a 41% decrease in the density of uterine receptors. Prolactin administration to pituitary intact rats was associated with a 50% increase in receptor density of adrenal glomerulosa simulating estradiol administration. However, the changes in glomeruli and uterine myometrium were opposite in that both tissues also increased receptor density, suggesting that prolactin was not the sole mediator of the estrogen-induced receptor changes. In conclusion, regulation of ANG II receptors in a number of diverse target tissues by estradiol is complex with contributions from estrogens and pituitary factors, which include but do not exclusively involve prolactin.
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PMID:Estrogen effects on angiotensin receptors are modulated by pituitary in female rats. 381 74

The effects of the catecholestrogen 2-hydroxyestradiol (250 and 500 micrograms/day, each for 7 days) on plasma renin substrate (PRS), activity (PRA) and concentration (PRC) were studied in male rats as compared with those of estradiol (250 micrograms/day, for 7 days) and vehicle alone (for 7 days). Pre-treatment levels of PRS, PRA, PRC and the PRA/PRC ratio were similar in four groups. After vehicle treatment, PRS, PRA, PRC and the PRA/PRC ratio remained unchanged. Estradiol treatment, however, produced an increase in PRS, an increase in PRA but no change in PRC. The PRA/PRC ratio after estradiol treatment was high. On the other hand, 2-hydroxyestradiol treatment caused no increase in PRS at a daily dose of 250 micrograms and a slight but significant increase in PRS at a daily dose of 500 micrograms. This treatment also produced increases in PRA as well as PRC at the two daily doses. These increases in PRA and PRC tended to be higher at a daily dose of 500 micrograms than at a daily dose of 250 micrograms. The PRA/PRC ratios after 2-hydroxyestradiol treatment were unaltered at the two daily doses. It is concluded that, while 2-hydroxyestradiol is less active in increasing PRS than estradiol, the compound is capable of increasing PRC.
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PMID:Effect of the catecholestrogen 2-hydroxyestradiol on the renin-angiotensin system in the rat. 676 95

A complete renin-angiotensin system has been shown to be present in human placenta, but its physiological role is poorly known. To investigate the implication of this system in the regulation of steroid hormone secretion, we studied the effect of angiotensin-II on the release of estradiol and progesterone from human placental explants. Our experiments showed that angiotensin-II stimulated estradiol secretion from term placental explants in a dose- and time-dependent fashion, although progesterone release was unaffected. Estradiol release induced by angiotensin-II (0.2 mumol/L) was blocked by angiotensin AT1 receptor antagonist losartan in a dose-dependent manner, suggesting the involvement of the AT1 receptor subtype in the process. On the contrary, the angiotensin AT2 receptor antagonist PD123319 (1 mumol/L) or the angiotensin AT2 receptor agonist CGP42112A (1 mumol/L) had no effect. Analysis of the amount of steroid hormones in the placental tissues incubated for 12 h showed that angiotensin-II increased estradiol production by 34% compared with the unstimulated explants, whereas the total levels of the estrogen precursor androstenedione and testosterone were decreased by 30-45% in the presence of the peptide, suggesting a stimulatory effect on the aromatization step. This hypothesis was reinforced by the absence of effect of angiotensin-II on both estradiol and testosterone concentrations in the placental explants pretreated with the aromatase inhibitor 4-hydroxyandrostenedione (25 mumol/L). Progesterone synthesis was not affected by angiotensin-II. The present study indicates that angiotensin-II induces the secretion of estradiol from human placenta through the angiotensin AT1 receptor subtype activation, and this effect seems to be linked to the stimulation of local androgen aromatization.
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PMID:Angiotensin-II stimulates estradiol secretion from human placental explants through AT1 receptor activation. 771 93

The renin-angiotensin-aldosterone system (RAAS) is one of the main systems involved in the regulation of blood pressure and sodium homeostasis. In animal experiments and in humans, the plasma renin activity and aldosterone levels are reduced with aging. The age-related differences in plasma renin activity and aldosterone are more pronounced in stimulated conditions (when sitting in an upright position, when salt intake is restricted and when plasma volume is depleted) than under basal conditions. Age-related alterations of the kidney (glomerulosclerosis, decreased number of functional nephrons) might account for the age-related differences in the active to inactive plasma renin ratio. In the same way, a diminished synthesis of angiotensinogen by the liver could contribute to the decrease in the activity of the RAAS in aging. This is partially compensated for by increases in the density of angiotensin II receptors reported in elderly patients. Furthermore, aging is associated with a reduced adrenal responsiveness to angiotensin II, contributing to lower production of aldosterone and alterations of sodium homeostasis. Estradiol and progesterone help stimulate the secretion of renin. Reduced levels of these hormones at menopause also lead to reduced plasma renin activity. In relation to these findings, several studies have shown that reductions in blood pressure, induced by short or long term treatment with angiotensin converting enzyme (ACE) inhibitors, were more pronounced in old than young hypertensive patients. An insertion/deletion polymorphism in the ACE gene has been described; the genotype deletion/deletion of this gene has been reported to be closely associated with longevity. This result was unexpected since the same deletion polymorphism was also shown to represent a potent risk factor for myocardial infarction.
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PMID:Changes in the renin-angiotensin-aldosterone axis in later life. 783 91

Previous work has demonstrated contraceptive steroid-induced hypertension in rats. Here, we examined the relationship between steroid-induced hypertension and components of the renin-angiotensin system. Female Sprague-Dawley rats were injected s.c. with 0.2 micrograms ethynyloestradiol, 2.0 micrograms levonorgestrel, a combination of both or vehicle, six days per week. A second group of rats received 2.0 micrograms enalapril maleate, enalapril plus ethynyloestradiol or levonorgestrel, or vehicle. Systolic blood pressure increased with both ethynyloestradiol. (6 weeks, +17 mmHg; 12 weeks, +32 mmHg) and levonorgestrel (6 weeks, +24 mmHg) treatment. This effect of levonorgestrel was attenuated by co-administration of enalapril, which also reversed the hypertension seen with ethynyloestradiol. Ethynyloestradiol, but not levonorgestrel treatment caused a significant increase in plasma renin concentration, plasma renin activity, and plasma angiotensin II at both 6 and 12 weeks. Plasma renin substrate was increased by ethynyloestradiol at 3, 6 and 12 weeks, prior to the observed increase in systolic blood pressure. Combined steroid treatment had less pronounced effects. Enalapril alone or in combination with ethynyloestradiol decreased plasma renin concentration, activity and angiotensin II, and in combination with levonorgestrel decreased plasma renin concentration, substrate and activity (6 weeks only) but not angiotensin II. The data indicate a positive relationship between hypertension and the renin-angiotensin system with ethynyloestradiol, but not levonorgestrel treatment in rats.
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PMID:Effect of contraceptive steroid and enalapril treatment of systolic blood pressure and plasma renin-angiotensin in the rat. 795 Nov 67


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