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18-Hydroxycorticosterone

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Carl-joachim Partsch – One of the best experts on this subject based on the ideXlab platform.

Felix G. Riepe – One of the best experts on this subject based on the ideXlab platform.

  • Chromatographic system for the simultaneous measurement of plasma 18-hydroxy-11-deoxycorticosterone and 18-Hydroxycorticosterone by radioimmunoassay: reference data for neonates and infants and its application in aldosterone-synthase deficiency
    Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2003
    Co-Authors: Felix G. Riepe, Nils Krone, Michael Peter, Carl-joachim Partsch
    Abstract:

    Abstract A new chromatographic system for the steroid precursor separation and a sensitive radioimmunoassay system for the subsequent measurement of 18-hydroxy-11-deoxycorticosterone and 18-Hydroxycorticosterone has been developed. 18-Hydroxy-11-deoxycorticosterone and 18-Hydroxycorticosterone were extracted with methylene chloride and separated from cross-reacting steroids by Sephadex LH-20 column chromatography. Anti-18-hydroxy-11-deoxycorticosterone and anti-18-Hydroxycorticosterone antibodies raised in rabbits were used. The lower detection limit of the assay is 0.03 nmol/l and 0.128 nmol/l for 18-hydroxy-11-deoxycorticosterone and 18-Hydroxycorticosterone, respectively. Normal values for this assay in 128 healthy neonates and infants aged 0–5 months were established as a basis for the early hormonal diagnosis of aldosterone synthase deficiency types I and II. Its application for the diagnosis of aldosterone synthase deficiency is demonstrated in two patients with homozygous mutation/deletion in the encoding CYP11B2 gene.

Celso E. Gomez-sanchez – One of the best experts on this subject based on the ideXlab platform.

  • 18-Hydroxycorticosterone, 18-Hydroxycortisol, and 18-Oxocortisol in the Diagnosis of Primary Aldosteronism and Its Subtypes
    The Journal of clinical endocrinology and metabolism, 2012
    Co-Authors: Paolo Mulatero, Stefania Morra Di Cella, Silvia Monticone, Domenica Schiavone, Maria Manzo, Giulio Mengozzi, Franco Rabbia, Massimo Terzolo, Elise P. Gomez-sanchez, Celso E. Gomez-sanchez
    Abstract:

    Context Diagnosis of primary aldosteronism (PA) is made by screening, confirmation testing, and subtype diagnosis (computed tomography scan and adrenal vein sampling). However, some tests are costly and unavailable in most hospitals. Objective The aim of the study was to evaluate the role of serum 18-Hydroxycorticosterone (s18OHB), urinary and serum 18-hydroxycortisol (u- and s18OHF), and urinary and serum 18-oxocortisol (u- and s18oxoF) in the diagnosis of PA and its subtypes, aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH). Patients The study included 62 patients with low-renin essential hypertension (EH), 81 patients with PA (20 APA, 61 BAH), 24 patients with glucocorticoid-remediable aldosteronism, 16 patients with adrenal inciincidentaloma, and 30 normotensives. Intervention and main outcome measures We measured s18OHB, s18OHF, and s18oxoF before and after saline load test (SLT) and 24-h u18OHF and u18oxoF. Results PA patients displayed significantly higher levels of s18OHB, u18OHF, and u18oxoF compared to EH and normal subjects; APA patients displayed s18OHB, u18OHF, and u18oxoF levels significantly higher than BAH patients. Similar results were obtained for s18OHF and s18oxoF. SLT significantly reduced s18OHB, s18OHF, and s18oxoF in all groups, but steroid reduction was much less for APA patients compared to BAH and EH. The s18OHB/aldosterone ratio after SLT more than doubled in EH but remained unchanged in APA patients. Conclusions u18OHF, u18oxoF, and s18OHB measurements in patients with a positive aldosterone/plasma renin activity ratio correlate with confirmatory tests and adrenal vein sampling in PA patients. If verified, these steroid assays would refine the diagnostic workup for PA.

  • Regulation of 18-oxocortisol and 18-hydroxycortisol by the renin-angiotensin system and ACTH in man
    The Journal of steroid biochemistry and molecular biology, 1993
    Co-Authors: Noriyoshi Yamakita, Celso E. Gomez-sanchez, Tomoatsu Mune, Hisashi Yoshida, Seiji Miyazaki, Keigo Yasuda, Toshiaki Nakai
    Abstract:

    Based on urinary excrexcretion studies the secretion of the cortisol derivatives, 18-oxocortisol and 18-hydroxycortisol are believed to be regulated by ACTH and to a lesser degree by the renin-angiotensin system. Plasma concentrations of 18-oxocortisol and 18-hydroxycortisol were measured during the simultaneous activation of the renin-angiotensin system and inhibition of ACTH secretion. Five healthy male subjects consuming a sodium diet ad libitum were studied. Blood was drawn at 0800 h after 1 h in the supine position. In the first set of experiments, the subjects remained in the supine position from 0800 to 1000 h with or without the oral administration of 2 mg dexamethasone at 0800 h. In the second set of experiments the subjects were placed in the upright position after drawing the 0800 h sample. The subjects were studied with and without dexamethasone administered at 0800 h. Blood was drawn again at 1000 h. Plasma levels of 18-oxocortisol, 18-hydroxycortisol, ACTH, plasma renin activity (PRA), cortisol, aldosterone and 18-Hydroxycorticosterone were measured by radioimmunoassay. None of these parameters changed during the 2 h in the supine position. 18-Oxocortisol, 18-hydroxycortisol, aldosterone, 18-Hydroxycorticosterone and PRA increased, but ACTH and cortisol did not change when the subjects were placed in the upright position. After dexamethasone administration, 18-oxocortisol, 18-hydroxycortisol, cortisol, aldosterone and 18-Hydroxycorticosterone decreased in the supine position and no increase occurred in 18-oxocortisol, 18-hydroxycortisol and 18-Hydroxycorticosterone in the upright position. PRA and aldosterone increased and ACTH and cortisol decreased in these subjects. 18-Oxocortisol and 18-hydroxycortisol were more dependent on ACTH regulation and less on the renin-angiotensin system than aldosterone.

Dirk Leysen – One of the best experts on this subject based on the ideXlab platform.

  • Application of a ligand-based theoretical approach to derive conversion paths and ligand conformations in CYP11B2-mediated aldosterone formation.
    Journal of computational chemistry, 2011
    Co-Authors: Luc Roumen, Bram Van Hoof, Koen Pieterse, Paj Peter Hilbers, Erica M. G. Custers, Ralf Plate, Marcel E. De Gooyer, Ilona P. E. Beugels, Judith M. A. Emmen, Dirk Leysen
    Abstract:

    The biosynthesis of the mineralocorticoid hormone aldosterone involves a multistep hydroxylation of 11-deoxdeoxycorticosterone at the 11- and 18-positions, resulting in the formation of corticosterone and 18-Hydroxycorticosterone, the final precursor of aldosterone. Two members of the cytochrome P450 11B family, CYP11B1 and CYP11B2, are known to catalyze these 11- and 18-hydroxylations, however, only CYP11B2 can oxidize 18-Hydroxycorticosterone to aldosterone. It is unknown what sequence of hydroxylations leads to the formation of 18-Hydroxycorticosterone. In this study we have investigated which of the possible conversion paths towards formation of 18-Hydroxycorticosterone and aldosterone are most likely from the ligand perspective. Therefore, we combined quantum mechanical investigations on the steroid conformations of 11-deoxdeoxycorticosterone and its ensuing reaction intermediates with Fukui indices calculations to predict the reactivity of their carbon atoms for an attack by the iron-oxygen species. Both F− and F0 were calculated to account for different mechanisms of substrate conversion. We show which particular initial conformations of 11-deoxdeoxycorticosterone and which conversion paths are likely to result in the successful synthesis of aldosterone, and thereby may be representative for the mechanism of aldosterone biosynthesis by CYP11B2. Moreover, we found that the most likely path for aldosterone synthesis coincides with the substrate conformation proposed in an earlier publication (Ref.2). To summarize, we show that on a theoretical and strictly ligand-directed basis only a limited number of reaction paths in the conversion of 11-deoxdeoxycorticosterone to aldosterone is possible. Despite its theoretical nature, this knowledge may help to understand the catalytic function of CYP11B1 and CYP11B2. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011

Nils Krone – One of the best experts on this subject based on the ideXlab platform.

  • Chromatographic system for the simultaneous measurement of plasma 18-hydroxy-11-deoxycorticosterone and 18-Hydroxycorticosterone by radioimmunoassay: reference data for neonates and infants and its application in aldosterone-synthase deficiency
    Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2003
    Co-Authors: Felix G. Riepe, Nils Krone, Michael Peter, Carl-joachim Partsch
    Abstract:

    Abstract A new chromatographic system for the steroid precursor separation and a sensitive radioimmunoassay system for the subsequent measurement of 18-hydroxy-11-deoxycorticosterone and 18-Hydroxycorticosterone has been developed. 18-Hydroxy-11-deoxycorticosterone and 18-Hydroxycorticosterone were extracted with methylene chloride and separated from cross-reacting steroids by Sephadex LH-20 column chromatography. Anti-18-hydroxy-11-deoxycorticosterone and anti-18-Hydroxycorticosterone antibodies raised in rabbits were used. The lower detection limit of the assay is 0.03 nmol/l and 0.128 nmol/l for 18-hydroxy-11-deoxycorticosterone and 18-Hydroxycorticosterone, respectively. Normal values for this assay in 128 healthy neonates and infants aged 0–5 months were established as a basis for the early hormonal diagnosis of aldosterone synthase deficiency types I and II. Its application for the diagnosis of aldosterone synthase deficiency is demonstrated in two patients with homozygous mutation/deletion in the encoding CYP11B2 gene.