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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using an accurate and sensitive assay for the human placental aromatase we have found apparent Km values for androstenedione (4-androstene-3,17-dione) and testosterone to be 14 +/- 4.0 nM and 41 +/- 12 nM respectively. These values were significantly different (p < 0.001). Analyses at substrate concentrations 5-10 fold above and below the Km values did not indicate any anomalous kinetic behavior. Mixed substrate experiments were consistent with a single enzyme metabolizing both steroids: each competitively inhibited the aromatization of the other, and the "Ki" values were the same as their apparent Km values. Sodium chloride (1.2M) significantly increased the rate of testosterone aromatization by decreasing its Km value and had no significant effect on the aromatization of androstenedione. However, in the presence of this salt testosterone still inhibited the aromatization of androstenedione competitively with a "Ki" equal to its apparent Km. Our data is therefore consistent with the proposal that human placental microsomes contain a single "high affinity" site for the aromatization of androstenedione and testosterone.
Steroids 1980 Nov
PMID:Substrate specificity of the placental microsomal aromatase. 745 98

Steroids enter target cells and bind to specific receptor proteins. These complexes translocate to the nuclei, bind to the chromatin, and alter gene expression. Recently, inactive progesterone receptors of the chick oviduct have been identified in this laboratory during the late winter which are not capable of translocating and binding to nuclear acceptor sites either in vivo or in a cell free assay. During this period the oviduct remains unresponsive to the steroid. The nuclear binding activity does return at the end of the season with a corresponding return of oviduct responsiveness to the steroid. Analysis of the active and inactive receptors of progesterone reveals no difference in sedimentation rates in high salt or in the affinity of the steroid for the receptor. The tissue levels of the inactive receptor, however, are about-one-half those of the active receptor. Quantitative analysis of the molecular species of the progesterone receptor separated by isoelectric focusing reveals two species for the active receptor preparations (an A species focusing at a pH of 7 and a B species focusing at a pH of 6). The A species was absent in the active receptor preparations which explains the lower amounts of total receptor in this group. Further studies have shown inactive progesterone receptors in the undeveloped oviducts and in the oviducts of estrogen withdrawn chicks. In these instances, the B species of the receptor is missing. The results suggest: (1)a novel regulation of steroid action may exist which acts by modulating the levels of one of the two receptor species (or possible subunits of a dimer); (2)the presence of a steroid receptor does not necessarily reflect that the receptor is functional; and (3)the biological activity of a steroid may be assessed via cell free nuclear binding assays or via analysis of the molecular species.
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PMID:Identification of biologically active and inactive steroid receptors. 746 Feb 67

It has been suggested that endogenous substances (known as ouabain-like factors, OLF), secreted from the central nervous system in response to salt and water retention, inhibit the cell membrane Na+/K+ pump in the renal tubules and reduce sodium reabsorption. However, by also acting upon vascular smooth muscle cells, they may induce cell Na+ and Ca++ accumulation, vasoconstriction and systemic hypertension. Recently, an endogenous Na+/K+ pump inhibitor was isolated from human plasma; this inhibitor is indistinguishable from the cardiac glycoside ouabain based on biochemical and immunological criteria. Its plasma concentration is close to the therapeutic range for ouabain (around 0.4 nmol/L). Since plant ouabain promotes natriuresis, vasoconstriction, and hypertension; endogenous ouabain may therefore control extracellular fluid volume and blood pressure. The highest plasma concentrations of endogenous ouabain and OLF were found in congestive heart failure, aldosterone producing adenoma, human and animal models of volume expanded hypertension (reduced renal mass and DOCA-salt hypertension), and in Milan hypertensive rats (MHS). Aldosterone antagonists (canrenone and canrenoate) exert both agonist and antagonist effects on the digitalis receptor site of the Na+/K+ pump. They are effective antihypertensive agents in animal models of hypertension sustained by OLF (reduced renal mass-Na+ and DOCA-salt hypertension in rats). Moreover, in a subgroup of essential hypertensives, 4 weeks of canrenoate administration reduced blood pressure, heightened red blood cell Na+/K+ pump activity, and antagonized ouabain-induced vasoconstriction. None of these effects was seen in the other hypertensives. These data suggest that aldosterone antagonists stimulate the Na+/K+ pump inhibited by endogenous ouabain and exert their antihypertensive action at least in part through this mechanism.
Steroids 1995 Jan
PMID:Ouabain-inhibiting activity of aldosterone antagonists. 779 94

Uninephrectomized rats maintained on 0.9% NaCl as drinking fluid and infused for 8 weeks with aldosterone 0.75 micrograms/h via subcutaneous osmotic minipumps respond with hypertension, cardiac hypertrophy, and both interstitial and perivascular cardiac fibrosis. Similar animals injected with desoxycorticosterone (20 mg/week), or the glucocorticoid antagonist RU 486 (2 mg/day) show interstitial cardiac fibrosis to a lesser degree than animals injected with aldosterone, and show perivascular fibrosis to a greater degree. These findings suggest that glucocorticoid antagonist activity may play a role in exacerbating perivascular collagen deposition in response to chronic mineralocorticoid and salt imbalance.
Steroids 1995 Jan
PMID:Adrenal steroids and cardiac fibrosis. 779 98

Pseudohypoaldosteronism is thought to be a rare salt-losing disorder, caused by resistance to the action of aldosterone. Defective aldosterone receptor binding is present in familial as well as sporadic cases and it has been suggested that the pathogenesis is due to a defect in the aldosterone receptor system. To date, however, molecular genetic analysis has been unable to identify a mutation in the aldosterone receptor gene itself. We have reviewed the findings in patients with pseudohypoaldosteronism, for clues which might enable us to identify the underlying pathogenesis. Although aldosterone receptor binding is regularly decreased or absent in monocytes of patients with pseudohypoaldosteronism, in some patients receptor protein can be detected with a fluorescence-labeled antibody. Receptor protein was detected in patients from familial autosomal dominant families and in sporadic cases, but was undetectable in two patients with the familial recessive form. To further elucidate the pattern of inheritance we studied the response of the renin-angiotensin-aldosterone system to the stimulation by sodium depletion in the familial autosomal dominant form and in two families with sporadic cases. In both "sporadic" families investigated, one parent and one sibling had an exaggerated response of renin and aldosterone to sodium depletion indicating a defect of sodium conservation apparent only during stress, leading to reclassification as familial cases. No additional family member in the "classical" autosomal dominant families responded abnormally to sodium depletion. These findings indicate that pseudohypoaldosteronism is unusually heterogeneous in its clinical, biochemical, and genetic presentations and findings and suggest that its pathogenesis is heterogeneous as well.
Steroids 1995 Jan
PMID:Familial pseudohypoaldosteronism: a review on the heterogeneity of the syndrome. 779 4

Pseudohypoaldosteronism (PHA) is characterized by salt-wasting and failure to thrive in the newborn, accompanied by high urinary levels of sodium despite hyponatremia, hyperkalemia and metabolic acidosis, elevation of plasma renin activity, and high plasma aldosterone levels. PHA patients are resistant to mineralocorticoid administration, but their symptoms ameliorate after a period of sodium supplementation, which can be discontinued in older subjects. Binding studies performed on mononuclear leukocytes of the family members affected by the disease have shown the absence of binding of [3H]aldosterone to the mineralocorticoid receptor (MR) in mononuclear leukocytes in two siblings and a marked reduction in another sibling and the father, suggesting either the absence of MR or a defect in the ligand binding domain of the MR in these patients. Molecular analysis of the MR in the members of this family did not reveal any major rearrangement or deletion of the MR gene. In addition, no mutation was found in the entire MR coding sequence by RT-PCR and direct sequencing of MR mRNA, and the semiquantitative RT-PCR analysis of the MR mRNA of one affected patient failed to show any quantitative abnormality in MR expression. These results do not exclude a molecular abnormality present in the MR gene being responsible for PHA. However, they indicate that in this family PHA is not related to a modification of the MR primary structure or to a major abnormality in MR expression.
Steroids 1995 Jan
PMID:Molecular characterization of the mineralocorticoid receptor in pseudohypoaldosteronism. 779 6

Glucocorticoid resistance results from incomplete but apparently generalized inability of glucocorticoids to exert their effects on their target tissues. The condition is associated with compensatory elevation of circulating ACTH and cortisol, with the former causing excess secretion of both adrenal androgens and adrenal steroid biosynthesis intermediates with salt-retaining activity. The manifestations of glucocorticoid resistance vary from asymptomatic to different degrees of hypertension and/or hypokalemic alkalosis and/or hyperandrogenism, caused by elevation cortisol and other salt-retaining steroids, and of adrenal androgens, respectively. In women, hyperandrogenism can result in acne, hirsutism, male type baldness, menstrual irregularities, oligoanovulation, and infertility; in men, it may lead to infertility; and in children to precocious puberty. Different molecular defects, such as point mutations or microdeletions of the highly conserved glucocorticoid receptor gene, alter the functional characteristics or concentrations of the intracellular receptor and cause glucocorticoid resistance. The extreme variability in the clinical manifestations of glucocorticoid resistance and its mimicry of many common diseases can be explained by different degrees of glucocorticoid resistance, differing sensitivity of target tissues to mineralocorticoids and/or androgens or both, and perhaps different biochemical defects of the glucocorticoid receptor. Mineralocorticoid resistance results from the inability of aldosterone to exert its effect on target tissues. The syndrome is associated with salt loss, hypotension, and hyperkalemic acidosis. We have cloned and sequenced the cDNA of five unrelated patients with this syndrome and have not found any mutations of pathophysiological significance that would explain the resistance of these patients to aldosterone.(ABSTRACT TRUNCATED AT 250 WORDS)
Steroids 1995 Jan
PMID:Syndromes of glucocorticoid and mineralocorticoid resistance. 779 8

Several characteristics of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY), make these homozygous strains particularly well suited for investigating the interactions of salt appetite, blood pressure control, and their neuroendocrine substrates. Appropriate genetic and developmental investigations of sources of variation in salt appetite, blood pressure, and their putative neuroendocrine substrates in these homozygous strains can provide valuable insights into fundamental mechanisms of disease, as well as factors controlling homeostatic behavioral and physiological processes. However, inappropriate use of these strains can produce misleading, although seductively plausible, conclusions regarding mechanisms. Selective inbreeding for hypertension has concentrated in SHR the "high pressure" allele for several genes that influence blood pressure, whereas breeding for normal blood pressure has left WKY with the "normal pressure" allele for all or most of these genes. In principle, inbred hypertensive strains could provide information about specific genetic alterations that mediate the hypertensive phenotype. The benefits of work with these strains are discussed, but several false assumptions and logical pitfalls are described that might cause misleading or erroneous interpretations of results from work with such strains. These problems illustrate the importance of the research strategy in elucidating the particular information that can be provided by these inbred animal models of hypertension. Two strategic approaches for studying hypertension and other genetically determined or influenced characteristics in inbred animal models such as SHR are discussed: cosegregation analysis for identifying or rejecting genetic linkage, and brain graft techniques for identifying brain specific genetic influences on cardiovascular or behavioral phenotypes. Examples of each approach are described.
Steroids 1993 Dec
PMID:Strategies for investigation of CNS mechanisms of phenotypic variation in blood pressure and salt appetite in genetic hypertensive rats. 811 15

The syndrome of primary pseudohypoaldosteronism (PHA) is a hereditary disease characterized by increased aldosterone secretion associated with clinical signs of hypoaldosteronism. These include salt wasting and failure to thrive in the newborn, high urinary sodium, hyponatremia, hyperkalemia, and metabolic acidosis. Plasma renin activity is usually elevated in association with aldosterone. The clinical manifestation of the disease is variable, including severely affected patients who may die in infancy and patients who are asymptomatic. The disease seems to result from a cellular resistance to mineralocorticoid action, which could be either generalized, or restricted to the kidney. The condition is inherited as an autosomal dominant or an autosomal recessive trait; however, sporadic cases have been described. In this paper we report a 20-year follow-up study of a French family affected by PHA and we discuss the pathogenesis of the disease.
Steroids 1994 Feb
PMID:The enigma of pseudohypoaldosteronism. 819 55

The synthesis and 14C-labeling of 3 alpha, 7 alpha, 12 alpha-trihydroxy-27-carboxymethyl-5 beta-cholestan-26-oic acid by two different approaches is described. One of them involves chain elongation of cholic acid via Wittig-Horner condensation of its formylated 24-aldehyde with tetraethyl phosphonoglutarate. The resulting cholestenoate, on deprotection and hydrogenation, affords the unusual C29 bile acid in good yield. An alternative procedure consists in a malonic ester synthesis starting from the formylated 24-alcohol which, after conversion into a mesylate, is reacted with sodium salt of 2-carboethoxy-gamma-butyrolactone. Alkaline hydrolysis, decarboxylation, esterification with diazomethane and selective tosylation of the newly introduced primary hydroxyl function give a C28 precursor, which is easily chain-elongated into a labeled or unlabeled C29 bile acid by reaction with cyanide and hydrolysis. Due to the easy lactonization of some of the C28 intermediates, the latter method provides a better way for introducing a C-29 label than the sequence usually employed for carboxyl labeling of bile acids and consisting in a decarboxylative halogenation of the parent acid followed by substitution of the norhalogenide with [14C]cyanide and hydrolysis. The structure of the synthesized acid or its dimethyl ester is confirmed by 13C nuclear magnetic resonance spectroscopy and mass spectrometry, and is also shown by gas liquid chromatography to be identified with an authentic sample of biosynthetic C29 dioic bile acid extracted from body fluids of Zellweger patients.
Steroids 1993 Aug
PMID:Synthesis and 29-14C-labeling of 3 alpha, 7 alpha, 12 alpha-trihydroxy-27-carboxymethyl-5 beta-cholestan-26-oic acid. A bile acid occurring in peroxisomal diseases. 821 84


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