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)

The aim of the present work was to study the relationship between sex hormones and plasma renin levels during the oestrous cycle in a Wistar-derived rat strain. Plasma renin activity (PRA) as well as a plasma renin concentration (PRC) were increased during the day of oestrus in rats with controlled 4-day oestrous cycles. This increase in PRA and PRC was not found when rats were ovariectomized on dioestrus day 2 and samples measured on the expected day of oestrus. The increase in PRA and PRC was not found when normal cyclic rats were treated with either tamoxifen or the progesterone receptor blocker RU 38486. Treatment with progesterone at pro-oestrus after ovariectomy on dioestrus day 2 partially increased the PRA and PRC when compared with the values found during the day of oestrus in control rats. The combined treatment of ovariectomized rats on dioestrus day 2 with oestrogen and progesterone restored the normal increase in PRA and PRC values on the expected day of oestrus. We therefore postulate that the sodium diuresis promoted by progesterone may be modulated by the previous peak of oestrogen. However, stimulation of extrarenal sources of renin cannot be excluded nor can an involvement of inactive precursors of renin in the fluctuations of active renin that occur during the oestrous cycle. No important change in plasma renin substrate (PRC) was observed during the oestrous cycle. PRA, PRC and PRS were determined every 4 h during the 4-day oestrous cycle. Our results clearly show a rhythmic variation in PRA and PRC which increases during the day of oestrus with a peak at 06.00 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclical changes in plasma renin during the oestrous cycle in the rat: synchronized effect of oestrogen and progesterone. 266 56

A large amount of renin mRNA was found to be expressed in the juxtaglomerular cell (JGC) tumor, as determined by Northern analysis. We have isolated the long 5'-flanking region of the human renin gene from the tumor, and characterized the promoter region with respect to nucleotide (nt) sequence and mRNA transcription start point. Of two sets of CAAT and TATA box at 29 bp upstream from the capping site is demonstrated to be a functional promoter by the primer extension. The 1:6-kb sequence, containing the 5'-flanking region, exon 1, and part of the first intron, obtained from the tumor was in complete agreement with that of the clone from fetal liver, which does not produce renin. This indicates that abnormal expression of the human renin gene in the JGC tumor involves no major alteration in the primary structure within 1.2 kb of the 5'-flanking region. Within 1.2 kb of the 5'-flanking region, there are several nt segments exhibiting homology with the glucocorticoid, estrogen, and progesterone receptor-binding sites and enhancers. These structures may be related to the tissue-specific expression of the renin gene.
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PMID:Human renin gene of renin-secreting tumor. 303 46

An estrogen receptor and an androgen receptor are present in the mammalian liver. In the liver of the rat, the estrogen receptor concentration increases markedly at puberty and this change correlates with enhanced estrogen stimulation of plasma renin substrate synthesis. High doses of estrogen are required for nuclear binding in liver when compared to doses for the uterus. The high dose requirement appears to be predominantly due to extensive metabolism in the hepatocyte of the estrogen to inactive derivatives. Furthermore, estradiol is much weaker than ethinyl estradiol for promoting nuclear binding in the liver. This is due to extremely rapid and extensive metabolism of estradiol. In human liver the concentration of estrogen receptor is low. An androgen receptor is present in high concentration in rabbit liver and is located predominantly in the nucleus after androgen administration. High concentrations of a putative androgen receptor are also present in human liver cytosol. Preliminary studies indicate that synthetic progestins can attach to the human liver androgen receptor. To date, a progesterone receptor has not been found in the mammalian liver. Thus, it appears that extensive steroid metabolism in liver preferentially diminishes sex steroid interaction with liver receptors and that androgen receptors may mediate progestin effects in liver. These observations provide a scientific basis for improved safety of oral contraceptives. Lowering the estrogen and progestin doses in oral contraceptives will decrease the major side-effects, which are liver mediated, and still maintain the desired effects at the hypothalamic-pituitary axis and uterus. Furthermore, it is likely that by selecting which estrogen, progestin or androgen is administered as well as by utilizing a parenteral route of administration that sex steroid effects on the liver could be minimized.
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PMID:Estrogen receptors and androgen receptors in the mammalian liver. 332 May 48

It is vital that we maximize compliance if patients are to receive the full benefits from hormone replacement therapy (HRT). One of the main factors for reduced compliance is that of progestogen intolerance. Progestogens have a variety of effects apart from the one for which their use was intended, that of secretory transformation of the endometrium. Endometrial effects vary between individuals and between different progestogens, leading to bleeding problems. Symptoms of fluid retention are produced by the sodium-retaining effect on the renin-aldosterone system. The nor-testosterone-derived progestogens can have adverse effects on skin, lipids, vasculature and insulin resistance. Negative mood effects are produced by most progestogens due to the effect on neurotransmitters via central nervous system progesterone receptors. Manipulation of the dosage and duration of progestogen, continuous administration of a low dose of progestogen and a reduction in the number of progestogenic episodes can be used to improve compliance. The progestogen and progesterone releasing coils and vaginal progesterone gel minimize systemic side effects and bleeding. Adverse effects can also be avoided by making use of the progesterone receptor-specific progestogens such as the pregnanes (e.g. cyproterone), nor-pregnanes (e.g. nomegestrol) and progesterone itself. Hysterectomy remains an option for the severely progestogen-intolerant woman. In the future, progestogen intolerance may not be an issue if selective oestrogen receptor modulators provide a complete alternative to HRT.
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PMID:Progestogen intolerance and compliance with hormone replacement therapy in menopausal women. 928 39

Captopril (D-3-mercapto-2-methylpropanoyl-L-proline) is an angiotensin converting enzyme (ACE) inhibitor, used widely in the treatment of hypertension and congestive heart failure. Captopril also inhibits proliferation of a variety of cell types, including several lacking ACE and renin acitvity. We have previously demonstrated that human mammary ductal carcinoma cells are among the cell types whose mitotic activity is inhibited by captopril. In those cells, captopril also reduces estrogen receptor (ER) and increases progesterone receptor (PR) concentrations. The present study evaluated the mechanism of captopril's antiproliferative action in an ER/PR-negative human mammary ductal carcinoma cell line, Hs578T. Cells grown in a 10% serum medium showed negligible changes in the presence of captopril alone. However, in the presence of subphysiologic concentrations of copper salts or copper-loaded ceruloplasmin, captopril caused a dose-dependent reduction in cell number, thymidine incorporation and mitochondrial dehydrogenase activity. In contrast, iron salts and iron-saturated transferrin had no effect on captopril activity. Catalase and horseradish peroxidase nullified the cytotoxic effects of captopril/Cu++, whereas H2O2 mimicked those effects. These data are consistent with the notion of a copper-catalyzed oxidation of captopril, leading to the generation of H2O2 as the cytotoxin to this clinically important cell type.
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PMID:Mechanism of captopril toxicity to a human mammary ductal carcinoma cell line in the presence of copper. 1051 67

A number of synthetic progestogens are currently available which differ greatly among themselves in various ways. The common property of all progestogens is that they transform a proliferative endometrium into a secretory or luteal endometrium by fixing the progestogen or 1 of its metabolites to the progesterone receptor. Most progestogens also have a greater or lesser affinity for other hormonal receptors, and some cause modifications in metabolism, especially of lipids and glucose. Synthetic progestogens can be classified according to their chemical formulas, biologic properties, and efficiency in relation to hormone receptors, but none of the current classification systems is a satisfactory guide to use. It is not yet definitively known whether pro-hormones, which must be transformed into norethindrone in vivo before taking effect, are advantageous or disadvantageous for therapeutic use. Synthetic progestogens have been found to have varying metabolic effects according to their content and dosage; hepatic function, lipid metabolism, glucose metabolism, coagulation factors, and the renin-angiotensin-aldosterone system are among the functions affected. The metabolic effects of synthetic progestogens are the principal criteria of choice. High dose 19 norsteroids are recommended only for cancer treatment, 19 nor-pregnane derivatives and progesterone isomers appear suitable for treatment of conditions such as endometriosis, premenopausal menstrual irregularities, and menstrual irregularity resulting from luteal insufficiency in younger women. Low-dose 19 norsteroids remain the best choice for contraception. Levonorgestrel has been preferred over norethindrone for some time because it is effective at a dose of .150 mcg compared to 1 mg for norethindrone, but some recent research suggests that even at a much smaller dose, levonorgestrel may cause more metabolic modifications than norethindrone. The pro-hormones ethynodial diacetate and lynestrel have additional metabolic effects whose consequences are as yet unknown. Preparations containing levonorgestrel should be preferred until the expected appearance on the market of triphasic preparations containing norethindrone and desogestrel, which permit excellent cycle control. Among progestogen-only contraceptives, 10 mg/daily of lynestrenol is associated with high rate of side effects. Microdose synthetic progestogen preparations are sometimes useful but offer imperfect efficacy, poor cycle control, higher risk of extrauterine pregnancy and ovarian cysts, and creation of iatrogenic luteal insufficiency.
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PMID:[Choosing the right synthetic progestogen]. 1231 5

Aldosterone antagonists have been available for many decades for the treatment of hypertension, but their use has been mostly limited to patients with classic primary aldosteronism or to combination products with hydrochlorothiazide to minimize risk for hypokalemia. Recently, indications for aldosterone antagonists have been expanded to include congestive heart failure and first-line treatment of mild-to-moderate hypertension. In addition, we have reported that spironolactone has significant antihypertensive benefit when added to existing regimens in patients with resistant hypertension. This benefit was present in patients with and without hyperaldosteronism and was additive to chronic renin-angiotensin blockade with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs). Eplerenone, a selective aldosterone antagonist, avoids the androgen and progesterone receptor-related adverse events that sometimes occur with spironolactone, such as breast tenderness, gynecomastia, sexual dysfunction, and menstrual irregularities. In clinical trials, eplerenone has been shown to have antihypertensive benefit in treating mild-to-moderate hypertension similar to other widely used classes of agents. With recent demonstrations of benefit in multiple segments of the hypertensive population, aldosterone antagonists represent emerging opportunity for controlling high blood pressure.
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PMID:Aldosterone antagonism: an emerging strategy for effective blood pressure lowering. 1591 92

Adipose tissue inflammation and insulin resistance are central to the pathogenesis of the metabolic syndrome. Spironolactone, an antagonist of mineralocorticoid receptor, glucocorticoid receptor and androgen receptor, and agonist of progesterone receptor, has anti-inflammatory activity. Blockade of the renin-angiotensin-aldosterone system has been shown to improve glucose metabolism. We have investigated whether spironolactone has direct effects on glucose uptake and interleukin-6 secretion in human adipocytes. Spironolactone, but not its active metabolite canrenoic acid, significantly increased basal and insulin-stimulated glucose uptake in cultured IN VITRO-differentiated adipocytes of women, without affecting insulin sensitivity. The effect was not due to changes in abundance of glucose transporters 1 or 4 or in degree of cell differentiation. Spironolactone, but not canrenoic acid, significantly reduced basal interleukin-6 secretion by cultured stromal-vascular cells. These effects of spironolactone were not mediated by ligand-dependent antagonism of the mineralocorticoid, glucocorticoid, or androgen receptors. Spironolactone may have a novel role in increasing glucose uptake into adipose cells and attenuating adipose tissue inflammation, with implications for management of metabolic syndrome.
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PMID:Effects of spironolactone on glucose transport and interleukin-6 secretion in adipose cells of women. 1807 71

Steroid cell tumor, not otherwise specified (NOS), are rare ovarian tumor, in addition, it is more rare in children. The majority of these tumors produce several steroid hormones, particularly testosterone. Estrogen also secreted by steroid cell tumor, NOS, but it is uncommon. Furthermore, hypertension is an infrequent sign in steroid cell tumor, NOS. An 8.5-yr-old girl with hypertension and frequent vaginal spotting visited at our clinic. On laboratory evaluation, secondary hypertension due to an elevated plasma renin level and isosexual pseudoprecocious puberty was diagnosed. Right solid ovarian mass was detected in radiologic tests. She underwent a right ooporectomy and it revealed renin and progesterone receptor positive steroid cell tumor, NOS. After operation, her blood pressure returned to normal level and vaginal bleeding disappeared. Even though this case is very rare, when hypertension coincides with virilization or feminization, a renin-secreting ovarian steroid cell tumor, NOS, should be considered.
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PMID:Refractory hypertension and isosexual pseudoprecocious puberty associated with renin-secreting ovarian steroid cell tumor in a girl. 2165 74