Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five women with premature ovarian failure were studied in a randomized cross-over design to compare the biochemical effects of transdermal to oral estradiol administration when used in doses appropriate for endometrial preparation in a donor oocyte program. Patients randomly received increasing dosages of oral micronized or transdermal estradiol for 4 week, with progesterone added in the last 2 weeks, to mimic a normal hormonal cycle. Serum samples were assayed throughout treatment and compared to those from normally cycling premenopausal controls. In general, serum estradiol remained within the normal range in both treatment groups, whereas peak serum estrone levels were 10-fold higher in the orally treated group than those in the transdermally treated group. Serum levels of sex hormone-binding globulin, thyroid binding globulin, and renin substrate were all significantly elevated by day 14 in the orally treated patients and unchanged in the transdermal subjects. While plasminogen was unaltered by either route of administration, antithrombin-III levels fell with both treatments. Changes in gonadotropin levels were similar in both groups, with suppression of FSH by the end of the simulated cycles, but not into the normal premenopausal range. In conclusion, both estrogen replacement regimens provided near-normal serum estradiol profiles. However, despite the relatively high doses necessary to mimic a hormonally normal cycle, the transdermal route did not significantly alter the hepatic parameters studied, suggesting that this route of administration may have less adverse hepatic effects.
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PMID:Comparison of transdermal to oral estradiol administration on hormonal and hepatic parameters in women with premature ovarian failure. 190 93

The recent advances in our understanding of immunology have greatly improved our knowledge about the natural history of autoimmune diseases and, in particular, of autoimmune Addison's disease (Autoimmune AD). Autoimmune AD is a chronic disorder with a long preclinical period marked by the presence of adrenal cortex autoantibodies (ACAs). In this chapter the main data on this will be analyzed. The populations with the highest risk of Autoimmune AD are first relatives of patients with AAD and patients with autoimmune diseases, particularly those with chronic hypoparathyroidism or with premature ovarian failure. The best markers to identify the subjects at risk are ACAs detected by the immunofluorescence test on human or animal tissues, or 21-hydroxylase autoantibodies (21-OHAbs) detected by radioimmunoassay (RIA). The evaluation of adrenal cortex function in these individuals includes the basal determination of adrenocorticotropic hormone (ACTH), cortisol, aldosterone, plasma renin activity and cortisol after intravenous stimulation with synthetic ACTH. The multivariate analysis of the main factors (genetics, age, gender, titers of antibodies, pre-existing disease, status of the adrenal function) revealed that the risk of future AAD depends only on the presence of high antibody titers, chronic hypoparathyroidism or chronic candidiasis and adrenal dysfunction. On the basis of these parameters the risk of future Autoimmune AD can be calculated with an equation model. Patients with different risk scores need to be monitored at different time intervals, and those at high risk need to be strictly monitored and are the ideal subjects for future prevention trials.
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PMID:Adrenal cortex autoantibodies in subjects with normal adrenal function. 1582 24

Current hormone replacement therapy may not optimize cardiovascular health in women with premature ovarian failure. We compared the effects of physiological and standard sex steroid replacement regimens on cardiovascular health in these women. In an open-label, randomized, controlled crossover trial, 34 women with premature ovarian failure were randomly assigned to 4-week cycles of physiological (transdermal estradiol and vaginal progesterone) and standard (oral ethinylestradiol and norethisterone) therapy for 12 months. Cardiovascular health was assessed by 24-hour ambulatory blood pressure, arterial stiffness, and renal and humoral factors. Eighteen women (19 to 39 years of age) completed the 28-month protocol. Both regimens caused similar suppression of luteinizing hormone and follicle-stimulating hormone and provided symptom relief. In comparison with the standard regimen, physiological sex steroid replacement caused lower mean 24-hour systolic and diastolic blood pressures throughout the 12-month treatment period (ANOVA; P<or=0.0001 for both): systolic blood pressure was 7.3 mm Hg (95% CI: 2.5 to 12.0 mm Hg) and diastolic was 7.4 mm Hg (95% CI: 3.9 to 11.0 mm Hg) lower at 12 months. Although there were no differences in arterial stiffness, physiological sex steroid replacement reduced plasma angiotensin II (ANOVA; P=0.007) and serum creatinine (ANOVA; P=0.015) concentrations without altering plasma aldosterone concentrations. In comparison with a standard regimen, physiological sex steroid replacement in women with premature ovarian failure results in lower blood pressure, better renal function, and less activation of the renin-angiotensin system. These findings have major implications for the future cardiovascular health of young women who require long-term sex steroid replacement therapy.
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PMID:Cardiovascular effects of physiological and standard sex steroid replacement regimens in premature ovarian failure. 1933 57

The prevalence of left ventricular diastolic dysfunction (LVDD) sharply increases in women after menopause and may lead to heart failure. While evidence suggests that estrogens protect the premenopausal heart from hypertension and ventricular remodeling, the specific mechanisms involved remain elusive. Moreover, whether there is a protective role of estrogens against cardiovascular disease, and specifically LVDD, continues to be controversial. Clinical and basic science have implicated activation of the renin-angiotensin-aldosterone system (RAAS), linked to the loss of ovarian estrogens, in the pathogenesis of postmenopausal diastolic dysfunction. As a consequence of increased tissue ANG II and low estrogen, a maladaptive nitric oxide synthase (NOS) system produces ROS that contribute to female sex-specific hypertensive heart disease. Recent insights from rodent models that mimic the cardiac phenotype of an estrogen-insufficient or -deficient woman (e.g., premature ovarian failure or postmenopausal), including the ovariectomized congenic mRen2.Lewis female rat, provide evidence showing that estrogen modulates the tissue RAAS and NOS system and related intracellular signaling pathways, in part via the membrane G protein-coupled receptor 30 (GPR30; also called G protein-coupled estrogen receptor 1). Complementing the cardiovascular research in this field, the echocardiographic correlates of LVDD as well as inherent limitations to its use in preclinical rodent studies will be briefly presented. Understanding the roles of estrogen and GPR30, their interactions with the local RAAS and NOS system, and the relationship of each of these to LVDD is necessary to identify new therapeutic targets and alternative treatments for diastolic heart failure that achieve the cardiovascular benefits of estrogen replacement without its side effects and contraindications.
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PMID:Role of estrogen in diastolic dysfunction. 2441 72