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J M Villette

Publications and source records attributed to J M Villette.

At least 37 records · Page 2Linked to original sources
PubMed1996

Argon laser induced autofluorescence may distinguish between normal and tumor human urothelial cells: a microspectrofluorimetric study.

PURPOSE: To assess the ability of argon laser-induced autofluorescence spectroscopy (LIAFS) to discriminate normal from tumor human urothelial cells. MATERIALS AND METHODS: Emission spectra of single living cells excited at 488 nm. have been studied with confocal microspectrofluorimeter. RESULTS: Cellular autofluorescence appeared as a broad band with a maximum in the same "green" spectral range, 550 to 560 nm., probably corresponding to oxidized flavoprotein emission. However, the maximum autofluorescence intensity of normal urothelial cells was much higher, 10 times (p<0.0001) that of any of the tumor cell types tested. CONCLUSIONS: These results, suggesting a significantly reduced oxidized flavoprotein concentration in tumor urothelial cells, should prompt us to evaluate argon LIAFS as a potential tool to detect occult urothelial severe dysplasia and carcinoma in situ.

Argon↗
PubMed1996

Plasma neuroendocrine markers in patients with benign prostatic hyperplasia and prostatic carcinoma.

PURPOSE: Approximately 50% of all malignant prostatic tumors contain neuroendocrine cells, which cannot be attributed to small cell prostatic carcinoma or carcinoid-like tumors, and which represent only 1 to 2% of all prostatic malignancies. Only limited data are available concerning the plasma levels of neuroendocrine markers in patients with prostatic tumors. Therefore, we determine the incidence of high plasma levels of neuroendocrine markers in patients with benign and malignant prostatic disease. MATERIALS AND METHODS: The presence of elevated plasma neuropeptide levels was investigated in 135 patients with prostatic carcinoma and 28 with benign prostatic hyperplasia. Plasma chromogranin A, neurone-specific enolase, substance P, calcitonin, somatostatin, neurotensin and bombesin levels were analyzed by immunoassays, and were compared to clinical and pathological stages of disease. Plasma prostatic acid phosphatase and prostate specific antigen levels were also determined. All patients were followed for at least 2 years after inclusion in the study. RESULTS: Significantly elevated levels of chromogranin A were detected in 15% of patients with prostatic carcinoma before any treatment. During hormone resistant prostate cancer progression plasma chromogranin A and neuron-specific enolase levels were elevated in 55% and 30% of the patients, respectively. In patients with stage D3 disease survival curves were generated by the Kaplan-Meier method, and log rank analysis revealed a statistically significant difference between groups positive and negative for chromogranin A. Substance P and bombesin were also occasionally elevated in prostatic tumors. Determination of neuroendocrine differentiation by neuron-specific enolase or chromogranin A immunoassays was not helpful in the prediction of progressive localized prostatic carcinoma. CONCLUSIONS: Future studies of plasma neuropeptide levels should confirm whether these parameters can be used as prognostic markers during late progression of prostatic carcinoma or for the selection of patients suitable for evaluation of new antineoplastic drugs to be active against neuroendocrine tumors.

Acid Phosphatase↗
PubMed1995

Effect of oral isotretinoin treatment on skin androgen receptor levels in male acneic patients.

An oral daily dose (mean +/- SD, 0.75 +/- 0.05 mg/kg) of isotretinoin was administered for 3 months to six male patients with acne (scores of 4 and 5 according to Rosenfield). The therapy resulted in complete resolution of acne in four patients and improved acne significantly (score 1) in two patients. In accordance with recent findings, no change in serum testosterone and significant decreases in 5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol glucosiduronate, and androsterone glucosiduronate levels were observed after treatment. Androgen receptor status was investigated in back skin biopsies obtained in acne areas before and after 3 months of isotretinoin treatment. The treatment did not modify the binding affinity constant of skin androgen receptor (0.44 vs. 0.32 nmol/L), but it did induce a 2.6-fold decrease in its binding capacity constant (62 vs. 24 fmol/mg cytosolic protein), as assessed by Scatchard plot and confirmed immunologically by Western blot analysis. These data clearly showed that skin androgen receptor was sensitive to oral isotretinoin administration in acneic patients. The decrease in skin androgen receptor levels (this study) and the recently reported suppression of skin 5 alpha-dihydrotestosterone production by isotretinoin treatment appeared consistent with the involvement of androgen receptor and 5 alpha-dihydrotestosterone in the pathogenesis of acne. Indeed, sebum production is under androgen control, and an abnormal response of the pilosebaceous unit to androgens appears to be implicated in the pathogenesis of acne. These observations were consistent with the absence of sebum in complete androgen-insensitive patients and normal sebum production in male pseudohermaphrodites.

Acne Vulgaris↗
PubMed1994

Distinct androgen 5 alpha-reduction pathways in cultured fibroblasts and immortalized epithelial cells from normal human adult prostate.

All androgen-sensitive peripheral tissues and cells, including the prostate, are commonly believed to possess the ability to metabolize testosterone. We report on the in vitro metabolism of tritiated testosterone performed in immortalized human adult normal prostatic epithelial cells and in human adult normal prostate fibroblastic cells (stromal cells). These two cell types were incubated separately with increasing testosterone concentrations (1 to 50 nM.) for 2 and 4 hours, after which the testosterone metabolic profile was analyzed. Data analysis provided evidence, for the first time, of the existence of two different 5 alpha-reduced metabolic pathways. Stromal cells preferred the androsterone pathway via the oxidative androstenedione formation, whereas epithelial cells preferred the reductive 5 alpha-dihydrotestosterone pathway. These two 5 alpha-reduced metabolites were produced in nearly equal quantities regardless of testosterone concentration or time of incubation. Since interactions between epithelial and stromal cells are involved in the development of the prostate, the availability of defined epithelial and stromal cells suitable for in vitro experiments provides a useful tool for the study of the contribution of androgens to these interactions. The model presented in this study would permit a better evaluation of the intraprostatic regulation of androgen metabolism and the contribution of the anti-5-alpha-reductase drugs to the management of benign prostate hyperplasia.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1994

The application of a new highly-sensitive radioimmunoassay for plasma 21-deoxycortisol to the detection of steroid-21-hydroxylase deficiency.

21-deoxycortisol (21-DF) is a steroid of strictly adrenal origin formed by the 11-hydroxylation of 17-hydroxyprogesterone. This metabolic pathway is minor in normal subjects, in whom basal plasma concentrations range from 0.03 to 0.63 nmol/L and from 0.865 to 1.50 nmol/L after adrenocorticotrophic hormone (ACTH; Synacthène Immédiat, Ciba/Geigy, France). However, this metabolic pathway becomes major in 21-hydroxylase-deficient patients: in those who have the classical form of congenital adrenal hyperplasia (CAH) basal plasma 21-DF levels can attain more than 144 nmol/L. The synthesis of two isomers, E and Z, of the 21-deoxycortisol-3-carboxymethyloxime (CMO) hapten enabled us to prepare the corresponding E and Z immunogens by coupling them to bovine serum albumin (BSA), as well as the corresponding iodinated E and Z 21-DF-3-CMO-histamine tracers. We developed a very sensitive radioimmunoassay for 21-DF in plasma by associating an anti-21-DF-3-CMO-BSA-E isomer antibody to an iodinated 21-DF histamine-Z isomer (standard curve IC 50 = 8 pg/tube). This plasma 21-DF radioimmunoassay allowed diagnosis of the classical form of CAH in untreated newborn (basal 21-DF levels greater than 144 nmol/L), as well as the late-onset form (post-ACTH 21-DF levels greater than 11.54 nmol/L), and also permitted detection of 21-hydroxylase-deficient heterozygotes of both forms of CAH among the general population (post-ACTH 21-DF levels between 2.02 and 9.52 nmol/L).

Adolescent↗
PubMed1994

Evidence for decreased androgen 5 alpha-reduction in skin and liver of men with severe acne after 13-cis-retinoic acid treatment.

To investigate the effect of 13-cis-retinoic acid (13-cis-RA) treatment on androgen metabolism in men with severe nodulocystic acne, eight men with severe acne received an oral daily dose of 0.7 mg/kg 13-cis-RA over 3 months. Exploration of androgen metabolism in serum samples, 24-h urine collections, and skin biopsies obtained before and at the end of the treatment revealed no significant alterations in serum levels of either adrenal or gonadal androgens. However, the treatment did induce significant decreases in serum levels of the 5 alpha-reduced androgens: 5 alpha-dihydrotestosterone (P < 0.02), androsterone glucosiduronate (P < 0.04), and 5 alpha-androstan-3 alpha, 17 beta-diol glucosiduronate (P < 0.004). Unlike serum, the urinary 5 alpha-reduced metabolites 5 alpha-androstan-3 alpha, 17 beta-diol and androsterone did not vary significantly despite a decrease in the excretion of the latter. Moreover, a marginally significant increase in urinary excretion of etiocholanolone, very similar to the decrease in androsterone excretion, was observed. The ratio of androsterone to etiocholanolone decreased significantly (P < 0.004) after 13-cis-RA therapy and suggested a metabolic deviation from the androgen 5 alpha- to 5 beta-reduction pathway in the liver. The most pronounced effect was observed in skin biopsies, which lost 80% of their ability to form 5 alpha-dihydrotestosterone (P < 0.001). It is concluded that 13-cis-RA therapy in men with severe nodulocystic acne did not alter gonadal or adrenal functions, but it did induce 1) a highly significant decrease in 5 alpha-dihydrotestosterone formation by skin biopsies; 2) significant decreases in serum 5 alpha-dihydrotestosterone, androsterone glucosiduronate, and 5 alpha-androstan-3 alpha, 17 beta-diol glucosiduronate; and, finally, 3) deviation of the liver androgen 5 alpha- to 5 beta-reduction pathway. The effect of 13-cis-RA treatment on severe acne is consistent with the dramatic decrease in androgen 5 alpha-reduction observed mainly in the skin.

Acne Vulgaris↗
PubMed1994

Hirsutism and acne in women: coordinated radioimmunoassays for eight relevant plasma steroids.

We developed and validated a coordinated set of RIAs for the following eight steroids in single small aliquots (< or = 1 mL) of plasma: androstenedione, dehydroepiandrosterone, 11-deoxycortisol, 21-deoxycortisol (21-DF), 11 beta-hydroxyandrostenedione, 17 alpha-hydroxypregnenolone (17-Hpreg), 17 alpha-hydroxyprogesterone, and testosterone. Samples were extracted and then chromatographed on celite microcolumns. Radioiodinated tracers were used for two of the assays (17-Hpreg and 21-DF). Tritiated tracers and scintillation proximity assay counting were used to give separation-free procedures for the other six assays, which considerably improved their practicability and reproducibility. The basal and postadrenocorticotropic hormone plasma values for these steroids in normal women sampled in the follicular phase are presented. Finally, the measurement of the eight steroids as a diagnostic method is evaluated with reference to data from 203 patients with hirsutism and (or) acne.

17-alpha-Hydroxypregnenolone↗
PubMed1993

Enzyme-catalyzed synthesis of radiolabeled 5-pregnen-3 beta-ol-20-one sulfate.

The enzymatic synthesis of [3H]5-pregnen-3 beta-ol-20-one sulfate using [3H]5-pregnen-3 beta-ol-20-one, 3'-phosphoadenosine-5'-phosphosulfate and hydroxysteroid sulfotransferase 1 purified from rat liver is reported. The described procedure allowed the obtainment of high specific activity [3H]5-pregnen-3 beta-ol-20-one sulfate in yields ranging from 78 to 86% with respect to [3H]5-pregnen-3 beta-ol-20-one. Two-dimensional thin-layer chromatography was used to purify [3H]5-pregnen-3 beta-ol-20-one sulfate which upon solvolysis resulted in the formation of [3H]5-pregnen-3 beta-ol-20-one. The identity both of the synthesized compound and the solvolysed one was confirmed by reversed-phase high pressure liquid chromatography, and 2-dimensional thin-layer chromatography.

Animals↗
PubMed1993

Characterization of estrone sulfatase activity in human thrombocytes.

Estrone sulfatase is an important enzyme which catalyzes the production of estrone from estrone sulfate in a variety of human and animal tissues. We report, for the first time, on the presence of estrone sulfatase activity in thrombocytes from human blood. Incubation of [3H]estrone sulfate in the presence of human thrombocyte lysates resulted in the formation of [3H]estrone as assessed by two-dimensional TLC. Estrone sulfatase activity was localized in the mitochondrial-microsomal fraction in thrombocytes from human blood. The enzyme was thermostable and had an optimum pH of 5.60 in acetate buffer. The highest activity was obtained in the presence of 0.1% of either Nonidet P-40 or Triton X-100. Phosphate ions (1 mM) inhibited the enzyme activity by 64% and similar effects were observed in the presence of platelet-free plasma. Endogenous inhibitors had no effect on the observed enzyme activity under assay conditions as evidenced in this study. The apparent Km value was 3.16 +/- 0.08 microM for [3H]estrone sulfate and V was 188.5 +/- 2.6 (mean +/- SEM, n = 22) pmol.mg protein-1.h-1. Comparison between two thrombocyte preparative procedures provided evidence that thrombocyte estrone sulfatase activity should be measured in thrombocyte samples representing the whole thrombocyte population. This parameter appeared critical for accurate measurements of enzyme activity. The presence of estrone sulfatase activity in human thrombocytes provides a new non-invasive tool for the study of this activity both in physiological and pathological conditions which could be of potential clinical relevance.

Adult↗
PubMed1992

Prostaglandin E2 level in tissue surrounding aseptic failed total hips. Effects of materials.

Production of inflammatory mediators (IM) by cells and specifically macrophages around loosened implants may be responsible for their loosening. Our hypothesis was that different materials give rise to different amounts of these IM. It is thought that alumina/alumina for total hip replacement (THR), which has been used for 15 years in our orthopedic department, may produce less IM than other systems. We initiated a clinical prospective study to measure the level of prostaglandin E2 (PGE2) in tissue surrounding loosened prostheses to quantify PGE2 production regarding the types of material involved in the friction couple, i.e., alumina/alumina versus metal/polyethylene, and the type of fixation, i.e., cemented versus cementless. A total of 29 THR revisions were performed in 28 patients. Four implant groups were identified: alumina/alumina cemented, alumina/alumina cementless, metal/polyethylene cemented, and metal/polyethylene cementless. For each revision, tissues surrounding the failed implants were harvested and processed, and the PGE2 was measured in a blind manner using an immunoassay technique. As the measuring technique was difficult, at least three determinations for each sample were necessary. Some samples were excluded from the analysis for various reasons, for example, second or further revisions involving many different materials in the past, conjunction of metallic and alumina debris and samples taken from non-loosened components. Finally, 15 samples were considered adequate for inclusion in this study. Two groups were analyzed and compared: the alumina/alumina couple and the metal/polyethylene couple. Tissue surrounding the first group demonstrated a PGE2 level of 69 +/- 56 fmol/mg wet weight compared to 202 +/- 156 fmol/mg for the second.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetabulum↗
PubMed1991

Effects of insulin-like growth factor I (IGF-I) on enzymatic activity in human adrenocortical cells. Interactions with ACTH.

Cells obtained from 6 adult human adrenals or adrenal fragments were cultured in serum-free synthetic medium (McCoy's) in order to study the isolated effects of IGF-I on steroidogenesis and its interactions with ACTH. After addition of peptide, changes in the activities of steroidogenic enzymes were assessed by measuring certain steroids in the spent medium. These included pregnenolone, 17-hydroxypregnenolone (17-OH-Preg), dehydroepiandrosterone (DHA), 17-hydroxyprogesterone (17-OH-P), androstenedione (AD), 11-deoxycortisol and glucocorticoids (chiefly cortisol and its immediate precursors, 11-deoxycortisol and 17-OH-P) and cortisol itself. The steroid responses obtained with repeated doses of IGF-I (40 ng/ml approximately 10(-9) M), added at 0, 48 and 72 h, over 4 days' culture were quite different from those obtained with repeated doses of ACTH (0.25 ng/ml approximately 10(-10) M). All the steroids measured increased with time of culture under the influence of ACTH and, apart from pregnenolone which peaked, tended to reach a plateau. With IGF-I, by contrast, DHA, AD, 11-deoxycortisol and glucocorticoid production increased initially, then decreased progressively, whereas pregnenolone, 17-OH-Preg and 17-OH-P production was either absent or negative. Cumulative steroid production over 4 days reached similar levels in response to a single dose of IGF-I and/or ACTH, with two major exceptions: pregnenolone dropped significantly with IGF-I [46% +/- 6 (SEM) as opposed to 93% +/- 11 with ACTH, P less than 0.005, n = 5], as did 17-OH-P (48% +/- 11 vs 113% +/- 8 with ACTH, P less than 0.001, n = 6). Increased formation of down-stream metabolites (DHA, AD, 11-deoxycortisol and glucocorticoids) would suggest that IGF-I induced stimulation of the 17 alpha-, 21- and 11 beta-hydroxylases. The responses to ACTH stimulation of cells which 4 days previously had been pre-treated with an initial and single dose of IGF-I and/or ACTH emphasized the impact of IGF-I on the 3-hydroxylation steps in cortisol biosynthesis. Compared with ACTH pre-treatment, the effects of which faded in the long term, pre-treatment with IGF-I resulted in a significantly increased steroidogenic response (P between less than 0.05 and less than 0.01). With the single exception of pregnenolone (43% +/- 4.7), production of all the metabolites was amplified: 17-OH-Preg: 348% +/- 88; DHA: 643% +/- 127; 17-OH-P: 193% +/- 36; AD: 725% +/- 200; 11-deoxycortisol: 573% +/- 110; cortisol: 1000%.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex↗
PubMed1990

Greater conversion of testosterone to 5 alpha-dihydrotestosterone, reflecting increased peripheral 5 alpha-reductase activity in nude mice treated with high doses of cyclosporine A.

Following cyclosporine A (CsA) immunosuppressive therapy in kidney grafts, increased body hair growth (hypertrichosis and/or hirsutism) without significant variation in normal circulating plasma androgen levels (as observed in idiopathic hirsutism) has been reported by several authors. Other authors have described increased hair growth in nude mice treated with CsA. In order to evaluate the action of this drug in target tissues, using dorsal skin homogenates from nude mice treated with various doses of CsA, we measured the metabolic conversion of testosterone (T) to its 5 alpha-reduced products, reflecting 5 alpha-reductase activity (5 alpha-RA). Three groups of 5 female nude mice were treated with an oral suspension containing CsA 5 mg/kg (group 1), 25 mg/kg (group 2) and 100 mg/kg (group 3), respectively, and the results, including 5 alpha-DHT and Adiol formation, were compared with those obtained in a control group (n = 5) receiving only the olive oil vehicle. Cutaneous metabolic conversion of T was determined using tritiated T as substrate. After 1 h of incubation, 5 alpha-DHT and other 5 alpha-reduced products formed were separated and quantified using a reverse-phase chromatography column fitted to a flow-through radioactivity detector. Mean +/- SD 5 alpha-DHT formation (expressed as pmol per 100 mg of protein per h) was found to be increased in the treated groups (group 1: 3.17 +/- 0.37, group 2: 3.10 +/- 0.13, group 3: 4.26 +/- 0.20), respectively 7.5% (NS), 5.10% (NS) and 44.4% (P = 0.01) higher than in the control group (2.95 +/- 0.13). In addition to 5 alpha-DHT, enhanced formation of delta 4-androstenedione (delta 4), 5 alpha-androstan-3 beta,17 beta-diol (3 beta-diol) and 5 alpha-androstan-3 alpha,17 beta-diol (3 alpha-diol) were also observed in the treated groups. These results show a significantly increased formation of 5 alpha-DHT (and Adiol) in nude mice treated with high dose-levels of CsA.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1990

Increase in plasma 5 alpha-androstane-3 alpha,17 beta-diol glucuronide as a marker of peripheral androgen action in hirsutism: a side-effect induced by cyclosporine A.

Dose-dependent hypertrichosis is a common dermatological side-effect affecting the majority of patients treated with cyclosporine A (CSA). Previous studies have not demonstrated the influence of CSA on specific sex hormone levels. The aim of this study is to investigate whether CSA increases the activity of 5 alpha-reductase, an enzyme which transforms androgens into dihydrotestosterone in peripheral tissues. The metabolite which best reflects this activity is 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (Adiol G). The study was carried out on 49 insulin-dependent diabetes patients participating in the double-blind "Cyclosporine-Diabète-France" clinical trial, of which 28 were treated with CSA (16 males and 12 females), and 21 received only placebo (10 males and 11 females). All patients underwent extensive clinical and laboratory evaluations prior to and during the present study. In addition to Adiol G, testosterone (T), dehydroepiandrosterone sulfate (DHEA S) and sex hormone-binding globulin (SHBG) were assayed. Levels of Adiol G increased significantly in CSA-treated groups: males, 11.86 +/- 2.58 vs 7.83 +/- 2.30 nmol/l; females, 4.48 +/- 2.70 vs 2.10 +/- 1.22 nmol/l; P less than 0.02 (comparison of means). There were no significant differences in this parameter before and during treatment in either the male or female placebo groups (paired t-test). During the treatment period, T, DHEA S, SHBG and the T/SHBG ratio did not significantly change with respect to their baseline values in any of the groups studied (comparison of means). Comparison (using paired t-test) showed a significant increase of DHEA S in CSA-treated groups: males, delta = 3.08 +/- 3.33 nmol/l, P less than 0.01; females, delta = 0.98 +/- 1.13 nmol/l, P less than 0.05. In conclusion, it is possible that CSA induces hypertrichosis or hirsutism by increasing 5 alpha-reductase activity in peripheral tissues. Nevertheless the role of increased DHEA S as a possible Adiol G precursor cannot be excluded.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1990

Metabolic effect at six and twelve months of cyproterone acetate (2 mg) combined with ethinyl estradiol (35 micrograms) in 31 patients.

The metabolic effects of cyproterone acetate (2 mg) combined with a new dose level of ethinyl estradiol (35 micrograms) were studied over a one-year period in 31 patients presenting moderate clinical hyperandrogenism. The following tests were performed before treatment, at 6 and 12 months, an oral glucose tolerance test (OGTT) with measurement of insulinemia, total cholesterol, HDL cholesterol and the LDL + VLDL/HDL ratio, A1 and B apoproteins. At six months and at one year of treatment, the weight and body mass index (kg/m2) were not modified. Glucose tolerance and insulinemia had not changed significantly at one year. Lipid test results showed an increase in triglycerides, as well as in total and HDL cholesterol levels. However, the LDL + VLDL/HDL and A1/B apoprotein ratios did not change during the study. We conclude from these results that the new combination does not have any adverse effects on glucose tolerance and has a predominantly estrogenic effect on lipid parameters, characterized by increases in total cholesterol, HDL cholesterol and triglycerides.

Adolescent↗
PubMed1990

Androgen excess in women with acne alone compared with women with acne and/or hirsutism.

Acne is known to be one of the features of hyperandrogenism. The aim of the present work was to study women with persistent acne and without other evidence of hyperandrogenism, such as hirsutism, alopecia, or irregular menses. Among 87 female patients with acne and/or hirsutism, we defined three groups: group 1 (n = 29), patients having treatment-resistant acne without menstrual disturbance, alopecia, or hirsutism; group 2 (n = 27), patients with acne and hirsutism; and group 3 (n = 31), patients with hirsutism alone. Clinical chemistry criteria for hyperandrogenism were based on elevated values of one or more of the following parameters: plasma testosterone, delta-4-androstenedione, dehydroepiandrosterone, urinary 5 alpha-androstane 3 alpha-17 beta-diol, and 17-ketosteroids (with chromatography). Plasma and urine samples were drawn between the 18th and 25th days of the cycle. Among group 1 patients, we found 25 subjects (86%) with hyperandrogenism, according to these laboratory criteria. The etiologies were: polycystic ovary syndrome (36%), adrenal hypersecretion (40%, of which 12% showed secondary polycystic ovaries), isolated increase in 5 alpha-androstane 3 alpha-17 beta-diol (20%), and hyperandrogenism without diagnosis (4%). The parameters were found to be more elevated in these patients than in a control group of 30 normal volunteer women. In groups 2 and 3, the findings were essentially the same as in group 1, except for increased levels of testosterone and the testosterone/SHBG ratio. Furthermore, it was evident that persistent acne may be an isolated sign of hyperandrogenism.

Acne Vulgaris↗
PubMed1990

Circadian variations in plasma levels of hypophyseal, adrenocortical and testicular hormones in men infected with human immunodeficiency virus.

Alterations in the circadian time structure of the secretion of several hormones were investigated in 13 male patients infected with human immunodeficiency virus (HIV). Seven were asymptomatic (classified CDC II, according to the criteria of the Atlanta Centers for Disease Control), and 6 had acquired immunodeficiency syndrome (CDC IV). Ten healthy males volunteered as controls. Plasma levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), cortisol, testosterone, ACTH, and beta-endorphin were determined by RIA in blood samples obtained every 4 h from 0830-0830 h the next morning. Data were analyzed both by two-way analysis of variance and the cosinor method. Circadian rhythms were statistically validated for each of the six hormones in each of the three groups of subjects. Compared with the control subjects, mesors (24-h adjusted means) were significantly higher for cortisol and lower for DHEA, DHEA-S, and ACTH (P less than 0.001 for all four hormones) in all HIV-infected patients. Plasma testosterone mesors were similar in controls and CDC II patients, but decreased significantly in the CDC IV patient group (P less than 0.05). Analysis of the circadian rhythms of plasma hormone levels clearly indicated an altered adrenal hormonal state in HIV-infected male patients, even during the asymptomatic period of the infection. For instance, plasma cortisol at 0430 h was more than twice as high in HIV-infected patients as it was in time-qualified controls. Although patients already had elevated plasma cortisol and lowered adrenal androgen levels at this stage, hypogonadism was not observed, as gauged by plasma testosterone concentrations. We speculate that the primary hormonal defect in HIV-infected patients is increased cortisol secretion resulting from circadian-varying stimulation of the adrenal cortex by a factor other than pituitary ACTH. This factor might be a stimulating substance secreted primarily by infected immune cells. Excess cortisol would lower adrenal androgen secretion by shifting adrenal steroid biosynthesis toward glucocorticoids and decreasing pituitary ACTH secretion via a negative feedback mechanism.

Acquired Immunodeficiency Syndrome↗