Subnormal Plasma Adrenal Androgen Levels in Men with Uremia*

Zumoff, Barnett; Walter, Luiz Reynaldo de Figueiredo; Rosenfeld, Robert; Strain, James J.; Degen, Kathleen; Strain, Gladys; Levin, Joseph; Fukushima, David K.

doi:10.1210/jcem-51-4-801

Cited by 29 publications

(12 citation statements)

References 26 publications

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“…For instance, the excretion rates of the two main metabolites of testosterone, androsterone and etiocholanolone, were reduced in patients with chronic renal insufficiency as com¬ pared to healthy controls both in terms of absolute values and in terms of their contribution to total steroid excretion. This is in keeping with the re¬ duced plasma concentrations of testosterone com¬ monly encountered in these patients (15). Excre¬ tion rates of the four glucocorticoid metabolites were also reduced in terms of absolute values, but their share in total steroid excretion was similar to that in healthy individuals.…”

Section: Discussionsupporting

confidence: 83%

Impaired conversion of cortisol to cortisone in chronic renal insufficiency - a cause of hypertension or an epiphenomenon?

Vierhapper¹,

Derfler²,

Nowotny³

et al. 1991

Acta Endocrinologica

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To study the possible impairment of 11 \g=b\-hydroxysteroid-dehydrogenase in patients with chronic renal insufficiency, urinary excretion rates of the four main glucocorticoid-metabolites, tetrahydrocortisol, tetrahydrocortisone, allotetrahydrocortisol and allotetrahydrocortisone were determined by capillary gas chromatography in 22 patients with chronic renal insufficiency with (N=15) and without (N=7) hypertension, but without hemodialysis treatment. Whereas the sum of all 41 steroid metabolites determined by capillary gas chromatography was reduced (p<0.001) in patients with chronic renal insufficiency as compared with 22 healthy individuals, the relative contribution of the four glucocorticoid metabolites to total steroid excretion was similar in patients with renal insufficiency (22\m=+-\12%)and in healthy subjects (20\m=+-\5%).However, the excreted amount of tetrahydrocortisol exceeded that of tetrahydrocortisone in all but 3 (normotensive) patients with chronic renal insufficiency, but only in one healthy subject resulting, in patients with chronic renal insufficiency, in a ratio of tetrahydrocortisone vs tetrahydrocortisone of 0.7\m=+-\0.4 (hypertensive patients 0.5\m=+-\0.2; normotensive patients 1.1\m=+-\0.4;controls 1.9\m=+-\0.9,p<0.001 vs patients with chronic renal insufficiency). This ratio of tetrahydrocortisone/tetrahydrocortisol showed a correlation with serum concentrations of creatinine (p<0.001). These results provide indirect proof of an impaired conversion of cortisol to cortisone in moderate renal insufficiency and may suggest a relationship with the hypertension frequently seen in this group of patients.The binding affinity of the glucocorticoid cortisol to mineralocorticoid receptors in vitro equals that of aldosterone (1,2). However, in tissues with abun¬ dant activity of 1 lß-hydroxysteroid dehydrogenase (1 lß-OHSD) the potential mineralocorticoid activity of cortisol (2,3) is counteracted by local conver¬ sion of cortisol to the inactive steroid, cortisone (4), which is catalysed by this microsomal enzyme com¬ plex. The fact that the human kidney is an impor¬ tant site for the conversion of cortisol to cortisone (5) explains the aldosterone-selectivity of minera¬ locorticoid receptors of renal origin as opposed to structurally identical receptors located in the hip¬ pocampus and in the heart (1,6). Whereas renal 1 lß-OHSD protects the healthy kidney from the mineralocorticoid actions of cortisol, a defect in the cortisol-cortisone shuttle will cause hypertension. Indeed, congenital deficiency of 1 lß-OHSD, the

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Section: Discussionsupporting

confidence: 83%

Impaired conversion of cortisol to cortisone in chronic renal insufficiency - a cause of hypertension or an epiphenomenon?

Vierhapper¹,

Derfler²,

Nowotny³

et al. 1991

Acta Endocrinologica

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“…Free DHEA concentration in sciatic nerves is higher than that reported in human plasma (5,16) and is distinctly lower than that of free pregnenolone in the brain. Whether or not nerve DHEA derives from nerve pregnenolone cannot be deduced from these results, as in the case ofbrain steroids (4,17).…”

Section: Discussioncontrasting

confidence: 65%

Neurosteroids: pregnenolone in human sciatic nerves.

Morfin

Young

Corpéchot

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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The characterization and quantification of pregnenolone in human sciatic nerves were undertaken, following previous demonstration of the synthesis of this steroid in rat brain oligodendrocytes, to explore the hypothesis that Schwann cells may demonstrate the same biosynthetic activity. Pregnenolone was definitively identified by mass spectrometry and quantified by specific radioinmunoassay. Its concentration (mean ± SD, 63.9 ± 45.9 ng/g of wet tissue, n = 12) was 2100 times the plasma level and concentration found in tendons and muscle. No correlation was found with sex or age. Free dehydroepiandrosterone as well as sulfate and fatty acid esters of pregnenolone and dehydroepiandrosterone were also measured. Results are discussed in terms of the concept that these "neurosteroids" may be synthesized in the peripheral nervous system. Pregnenolone (3(3-hydroxy-A5-pregnen-20-one) accumulates in the rat brain independently of endocrine gland function, and its synthesis from cholesterol in oligodendrocytes has been demonstrated (1, 2), justifying the term "neurosteroid" (3). Measurements by radioimmunoassay have indicated that pregnenolone is present also in human brain and cranial nerves at levels similar to those in the rat (i.e., -0.1 ,umol/g of wet tissue) (4-6). Since (wt/vol) KOH for 1 hr at 80°C followed by 12 hr at room temperature. To measure the sulfated steroids present in the aqueous phase after isooctane/ethyl acetate extraction, solvolysis was performed in three cases as follows: the aqueous phase, once brought to pH 1 with sulfuric acid and made 20%o-NaCl, was extracted three times with ethyl acetate and the pooled extracts were incubated at 37°C for 16 hr. Further processing was carried out according to Burstein and Lieberman (9). Free steroids recovered in each of the free, saponified, and solvolyzed fractions were separated by partition chromatography on celite microcolumns before radioimmunoassay (4, 10). The addition of 3H-labeled steroids allowed appropriate corrections to be made for losses during the isolation procedures.Radioimmunoassays. Pregnenolone and DHEA and their respective sulfate and fatty acid esters were measured by radioimmunoassays using specific antibodies (5, 11). Measurements were made in triplicate on three dilutions of the fractions, thus allowing the construction of regression lines (measured picograms versus dilution) whose slopes gave the concentrations of steroids in the samples. Results were expressed as nanograms of steroid (free or released from conjugates) per gram of tissue, and standard deviations were calculated.Gas Chromatography-Mass Spectrometry (GC-MS). Unconjugated pregnenolone from sciatic nerves was identified by GC-MS. After individual measurements by radioimmunoassay of the fractions from the celite partition chromatography, the remaining unconjugated pregnenolone from three The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C...

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“…This may perhaps be explained by an increased stimula tion of testicular steroidogenesis from the elevated levels of LH. The pretransplant levels of DHA were low, a finding which previously has been demonstrated in pa tients with renal failure [16].…”

Section: Discussionsupporting

confidence: 61%

Ciclosporin-Associated Hypertrichosis Is Not Related to Sex Hormone Levels following Renal Transplantation

Lindholm

Pousette²,

Carlström

et al. 1988

Nephron

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To study a possible relationship between ciclosporin-induced hypertrichosis and sex hormone pattern, the hair growth in different areas of the body was graded and hormone levels were assayed before and up to 6 months after kidney transplantation. Increased hair growth was observed in 100% (23/23) of the patients in skin areas connected with androgen action and in 78% of the patients in androgen-insensitive areas. After renal transplantation the pituitary, testicular and adrenal hormone levels normalized. The posttransplantation levels of these hormones would not explain the observation of increased hairgrowth. Thus, ciclosporin induces hypertrichosis via a mechanism independent of sex hormones.

show abstract

Subnormal Plasma Adrenal Androgen Levels in Men with Uremia*

Cited by 29 publications

References 26 publications

Impaired conversion of cortisol to cortisone in chronic renal insufficiency - a cause of hypertension or an epiphenomenon?

Impaired conversion of cortisol to cortisone in chronic renal insufficiency - a cause of hypertension or an epiphenomenon?

Neurosteroids: pregnenolone in human sciatic nerves.

Ciclosporin-Associated Hypertrichosis Is Not Related to Sex Hormone Levels following Renal Transplantation

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