Biomedical subjects
Publications and source records attributed to M Pugeat.
A balanced reciprocal translocation t(1;Y) (q11;q11) was found in an infertile man with severe oligoasthenospermia. The same translocation was found in his father. The role of X-chromosome inactivation during meiosis in a male carrying a Y;autosome translocation is discussed.
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The aim of this study was to determine the impact of chronic treatment for 8 weeks with hydrocortisone acetate (5 mg kg-1 day-1) on skeletal muscles, and to evaluate whether sprint training can prevent glucocorticoid-induced muscle atrophy better than endurance training. Biochemical, histological and contractile properties were employed to determine the influence of this steroid on skeletal musculature, and the results were compared to pair-weight animals to take into account the influence of corticoids on growth rate. It was found that hydrocortisone acetate treatment results in a stunted growth, adrenal atrophy and depressed plasma corticosterone levels. Mild corticoid-induced losses of muscle mass and protein content (9%-13%) were observed in fast-twitch skeletal muscles. It appeared that the impact of corticoids is strictly directed toward type IIb fibres, which displayed a 12%-18% reduction in cross-sectional areas. No alterations occurred in plantaris contractile speed or tensions properties. Neither endurance training (30 m/min; 90 min/day; 5 days/week) nor sprint training (60 m/min; 15 min/day; 5 days/week) for 8 weeks was able to counteract the effects of corticoids. These data suggest that increased contractile activity, as induced by treadmill running, is not sufficient to counteract the muscular effects of glucocorticoids when administered at a dose of 5 mg kg-1 day-1.
OBJECTIVE: To explore the feedback regulation of glucocorticoids on corticotropin secretion in patients with septic and nonseptic circulatory shock. DESIGN: Prospective study. SETTING: An intensive care unit of a general hospital. PATIENTS: Two groups of patients with septic shock (n = 11) or nonseptic shock (n = 7). A control group (n = 20) was also studied. INTERVENTIONS: Intravenous dexamethasone (1 mg/hr for 4 hrs) suppression test. MEASUREMENTS: Plasma concentrations of corticotropin-releasing factor, beta-lipotropin, and corticosteroid-binding globulin measured by radioimmunoassays, and plasma cortisol measured by radiocompetition assay; the ratio of cortisol to corticosteroid-binding globulin calculated as the free cortisol index. MAIN RESULTS: In both groups of patients, the concentrations of plasma cortisol and beta-lipotropin, and the ratio of cortisol to corticosteroid-binding globulin, were higher than normal subjects (p < .001) and were not different between septic and nonseptic shock patients, whereas the plasma corticosteroid-binding globulin concentration was significantly (p < .001) lower in septic shock patients than in normal subjects (444 +/- 154 vs. 696 +/- 56 nmol/L [22.0 +/- 7.6 vs. 34.5 +/- 2.8 mg/L]), but not significantly lower in nonseptic shock patients (607 +/- 157 nmol/L [30.0 +/- 7.8 mg/L]). In contrast to the complete suppressive effect of dexamethasone infusion on cortisol and beta-lipotropin concentrations in normal subjects, dexamethasone did not suppress cortisol or lipotropin in either septic or nonseptic shock patients. CONCLUSIONS: During circulatory shock, hypercortisolism is associated with high concentrations of lipotropin, and is not suppressible by intravenous dexamethasone infusion.
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We have studied the response of prolactin (PRL) secretion to the test combining i.m. sulpiride in the dose 1 mg/kg followed by 200 micrograms i.v. of TRH, in 12 normal women and 37 patients with hyperprolactinaemia. The response was expressed as a percentage rise in plasma PRL concentration (delta %) 20 minutes after the administration of sulpiride or TRH. In the controls the response in PRL secretion to sulpiride worked out at between 639 and 2,760%. When there was a pituitary adenoma or supra-sellar lesion the PRL response to sulpiride was always less than 481%. On the other hand the PRL response with TRH after sulpiride was not significantly different as between the controls (less than 175%) and the patients (less than 91%). We conclude: 1) the combined sulpiride and TRH test is useless for assessing hyperprolactinaemia; 2) the sulpiride test on the other hand makes it possible to show that hyperprolactinaemia cannot be stimulated and to suspect the presence in this case of a prolactin producing adenoma or a supra-sellar tumour.
In humans, the plasma level of sex hormone binding globulin (SHBG) is regulated by several hormones. We have now accumulated evidence that SHBG is also intimately related to nutritional state. However, we do not yet know what specific signal, if any, may be the regulator of SHBG. There is a strong and negative correlation between fasting insulin level and SHBG in obese as in hyperandrogenic women. Under such circumstances, a high fasting insulin level, normal glycemia and a low SHBG level suggest insulin resistance in terms of glucose disposal but not in terms of SHBG inhibition. This is a rather complex situation. It is too early to judge the importance of IGF-I in the regulation of SHBG. But it may turn out that IGF-I is the main regulator of SHBG and that, by interaction with the IGF-I receptors, insulin carries on its inhibitory activity on SHBG.
OBJECTIVE: The aim was to explore the down-regulation of the glucocorticoid receptors during hypercortisolaemia in anorexia nervosa. DESIGN: Urine and plasma samples were obtained for cortisol determination and blood lymphocytes were isolated for receptor binding studies. PATIENTS: Sixteen anorexic patients, aged 16-27 years, with a mean +/- SEM body mass index of 14.2 +/- 2.0 (ranging from 11.1 to 17.4), and 15 normal women were studied. Six patients were reinvestigated after a significant weight gain. MEASUREMENTS: The binding capacity and affinity of the glucocorticoid receptors were measured with dexamethasone as ligand on lymphocytes. RESULTS: In patients, both total and free plasma cortisol concentrations were higher than in the normal women, as was their urinary free cortisol; the number of glucocorticoid receptors per cell (Ro) and the binding affinity (Kd) for dexamethasone were, however, not significantly different (Ro: 7687 +/- 1750 vs 7347 +/- 1285 sites/cell; Kd: 7.7 +/- 2.4 vs 7.4 +/- 1.7 nM at 24 degrees C). After weight gain (14 +/- 2 to 16 +/- 2 kg/m2), receptor numbers were 8421 +/- 2126 (pre) and 9011 +/- 500 (post) sites/cell, which are not significantly different (P greater than 0.2); the Kd was unchanged (9.3 +/- 2.6 vs 9.2 +/- 2.4 nM). CONCLUSIONS Hypercortisolaemia does not down-regulate the lymphocyte glucocorticoid receptors in anorexia nervosa and a post-receptor defect might be involved in peripheral tissue resistance to the effects of glucocorticoid hormones in undernutrition.
To identify the factor(s) involved in the decreased of sex steroid binding-protein (SBP) in hirsute women, we have investigated which parameters were in correlation with SBP in a population of 90 hirsute women. We found no significant correlation of SBP binding capacity with the plasma concentrations of the main androgens. Conversely, SBP was in inverse and significant correlation with body mass index and with the fasting insulin plasma level. These findings confirm that nutritional status must be considered in the physiopathology of hyperandrogenism in women. The control of overweight may be a goal for treating hirsutism in some patients.
The effects of oral administration of cyproterone acetate (CPA) (50 mg) associated with natural estrogens, was investigated in two groups of hirsute women. One group received 17-beta estradiol valerianate (E2) (2 mg) (n = 22) and the other, micronized E2 (2 mg) plus estriol (E3) (1 mg) daily (n = 22) for 21 days every month. After a six month period of treatment, hirsutism improved in 70% of the patients. The more frequent adverse effect was amenorrhea. Except in one, weight gain was prevented by a low calorie diet in overweight patients. During treatment, the plasma concentration of E2 was within the normal range for the follicular phase, whereas estrone was higher, and significantly (p less than 0.001) higher under E2 + E3 than under E2 alone (43.5 +/- 29.1 vs 23.9 +/- 6.1 ng/dl). The binding capacity of sex-steroid binding-protein (SBP) was increased by E2 + E3, and was not affected by E2; transcortin levels were unchanged during treatment. The plasma levels of SBP-unbound testosterone and of delta 4-androstenedione were significantly suppressed by CPA, while DHEAS was not significantly reduced. We concluded that oral administration of CPA and natural estrogens, is a well tolerated and efficient treatment of hirsutism.
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The antiandrogenic activity of spironolactone was used for treating hirsutism in 76 women, 29 of whom also had acne. Midcycle vaginal bleeding was observed in 21 patients under spironolactone 75 mg per day. This side-effect disappeared after a progestagen administered 10 days each month was added to the treatment. With this combination, spironolactone was well tolerated and effective in treating acne within the first months of administration, but in 61 percent of the patients at least 6 months were required to improve hirsutism.
The suppressive effect of dexamethasone (Dex) on plasma cortisol and beta-lipotrophin (beta LPH) was investigated in patients with anorexia nervosa. Dex was given either orally, 1 mg at 2400 h, with blood sampling at 0800 h on the days before and after Dex, or by i.v. infusion starting at 1100 h (1 mg/h) for 4 h with sampling at 0800, 1100, 1500, 2000 and 2400 h and at 0800 h the following day. The plasma cortisol and beta LPH levels during oral or i.v. Dex administration were compared between patients and normally menstruating women of normal weight. The results showed that Dex administration depressed cortisol significantly (P less than 0.0001) during oral or i.v. infusion in most patients, without, however, suppressing it entirely as is the case in normal women. Moreover, during i.v. Dex infusion, the concentrations of cortisol escaped suppression and were higher than in normal women (less than 50 nmol/l) by 0800 h on the day following infusion. In the patients who were reinvestigated after re-feeding and weight gain (n = 9), a normal suppression of cortisol in response to i.v. Dex infusion was observed in only five cases and a slight failure to suppress, although concentrations were lower than before refeeding, was still evident in four. We concluded that, in anorexia nervosa, cortisol concentration rapidly escapes suppression by Dex administration, and that this escape is not related to the degree of starvation.
Androgens are a family of steroids hormones secreted by the adrenal glands and the ovaries in women. The adrenal secretion of androgens becomes significant around the age of 7, at the onset of adrenal activity, and increases until ovarian puberty. The excess of adrenal androgens, of which the main products are dehydroepiandrosterone and its ester sulfate (DHEAS), is unrelated to a classic deficiency of steroid biosynthesis. Blocking with small doses of dexamethasone (0.5 then 0.25 mg at night), demonstrates that the DHEAS may be blocked and rules out a tumor of the adrenal cortex. This treatment, which presents tolerance problems, is effective on acne, but ineffective on hirsutism which requires the use of antiandrogens. In addition to this idiopathic adrenal hyperandrogenism, the late manifestations of a congenital deficiency in 21-hydroxylase in a clinical picture varying from a mere obesity to moderate hirsutism, but may evolve to a syndrome of polycystic ovaries, is easy to diagnose with a basic 17-hydroxyprogesterone assay. In this case, adrenal blocking by dexamethasone often gives a spectacular clinical result. Isolated ovarian hyperandrogenism, is found in the various clinical forms of the polycystic ovaries syndrome. Usually, this syndrome is suggested by the anovulation, cause of sterility, hirsutism and overweight. Ovarian ultrasonography is often difficult to explain, particularly because of the non-univocal macroscopic appearance of the ovaries. Therefore, a great deal of emphasis is placed on the hormonal exploration which shows an elevated concentration of serum testosterone (T) and mostly of delta-4 androstenedione (A), combined with an elevated luteinizing hormone (LH) which should be determined on several successive samples.(ABSTRACT TRUNCATED AT 250 WORDS)
Several antiandrogens compounds are available in the treatment of acne and hirsutism in women. Cyproterone acetate is the most effective antiandrogen. Its use must prevent the occurrence of amenorrhea with the prescription of an appropriate estrogen. Spironolactone, less effective, is better tolerated on a long-term basis, if precaution is taken to combine it sequentially with a progesterone or a norprogesterone, in order to avoid the occurrence of short cycles. This is the treatment of choice of moderate hirsutism or acne, in young patients. The association of spironolactone with an estroprogestative without nortestosterone is easy to use and well tolerated, and gives good results on acne and hirsutism.
Androgens are steroids with 19 carbon atoms located in the biosynthesis chain between progestives and estrogens. The main androgen is testosterone which is mostly the peripheral interconversion product of delta-4-androstenedione whose origin is mixed, from the ovary and the cortex of the adrenals. Dehydroepi-androsterone essentially comes from the adrenals and is accumulated in the form of a sulfate, the DHEAS, which is one the most concentrated circulating steroid. Although DHEAS only has a slight androgenic activity, the possibility of conversion into testosterone in certain target tissues, especially the skin, makes DHEAS a potential androgen to consider in testing and treating hyperandrogenic conditions. The circulating testosterone is, for the most part, bound to proteins and especially a protein having a strong affinity for testosterone and estradiol, the testosterone estradiol binding-protein (TeBG) or sex steroid binding-protein (SBP). The SBP originating from the liver is under the influence of numerous hormonal and non-hormonal parameters. Androgens decrease the binding ability of SBP, SBP modifies the metabolic clearance of the hormones it binds. Thus, measurement of the free testosterone fraction, not protein-bound, is a better index of the production of testosterone than the measurement of its total concentration. In addition, the fraction which is not bound to the SBP of testosterone is considered as the biologically active fraction, and has a good diagnostic value in the determination of a hyperandrogenic condition. In several target organs, testosterone, under the effect of 5 alpha-reductase, an enzyme whose activity is induced by androgens, is transformed in dihydrotestosterone of DHT which has more binding affinity for androgen receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
To measure the concentration of testosterone (T) that is not bound to sex-steroid-binding protein (SBP) in plasma, we quantified by radioimmunoassay the T in the supernates of plasma samples after precipitation with 50%-saturated ammonium sulfate. The concentrations of non-SBP-bound T. directly measured with this assay, correlated significantly (P less than 0.001) with those deduced from measurement of the percentage of non-SBP-bound T determined with [3H]T as tracer or from mathematical models according to the law of mass action. It also correlated significantly with the ratio of T to SBP and with the concentration of nonbound T. As determined with this assay, the mean concentration of non-SBP-bound T in normal men was higher in young (4.67, SD 2.68 nmol/L; n = 30) than in older (greater than 40 years) subjects (2.48, SD 1.61 nmol/L; n = 35; P less than 0.001) and lower than normal in hyperthyroid (1.61, SD 0.91 nmol/L; P less than 0.01) or infertile men (3.28, SD 1.70 nmol/L; P less than 0.01). In women, non-SBP-bound T was higher in hirsute patients (0.24, SD 0.11 nmol/L; P less than 0.01) and was lower during pregnancy (0.09, SD 0.05 nmol/L; P less than 0.05) than in normal women during the follicular phase (0.16, SD 0.07 nmol/L). We conclude that this direct measurement of non-SBP-bound T in plasma is suitable for routine use and represents a reliable index of androgenicity in human pathology, particularly when alterations of the binding capacity of SBP modify the concentrations of total T.