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Biomedical subjects

M Pugeat

Publications and source records attributed to M Pugeat.

At least 19 recordsLinked to original sources
PubMed1995

In vitro influence of plasma steroid-binding proteins on androgen metabolism in human leukocytes.

The purpose of this study was to investigate the influence of plasma steroid-binding proteins on androgen metabolism in intact leukocytes prepared from normal male and female blood samples. Leukocyte preparations were incubated for 24 h at 37 degrees C with either labeled or unlabeled testosterone (T), 5 alpha-dihydrotestosterone (5 alpha-DHT), and androstenedione (A). After extraction, the formed labeled metabolites were first identified by high performance liquid chromatography, then, using unlabeled substrates, metabolite concentrations were measured by specific radioimmunoassays. The conversion ratios of substrate to metabolite were calculated for each preparation using either labeled or unlabeled substrates. In the absence of steroid-binding proteins, the mean conversion ratios of T to A, A to T, T to 5 alpha-DHT, and 5 alpha-DHT to 3 alpha-androstanediol (3 alpha-D) were, in males and females, respectively, 5.6% and 6.1% (n = 11), 5.6% and 5.6% (n = 5), 2.8% and 2.2% (n = 11), 43.1% and 40.0% (n = 5), these sex differences being non-significant. The presence of increasing amounts of plasma, purified albumin or sex hormone binding-globulin (SHBG) in the incubation media reduced metabolite formation dose-dependently. However, a 1000-fold greater concentration of albumin than of SHBG was necessary for 50% inhibition of androgen metabolism by leukocytes, showing SHBG to have the main protective effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Interrelations between sex hormone-binding globulin (SHBG), plasma lipoproteins and cardiovascular risk.

The incidence of coronary artery disease is significantly higher in men than in women, at least until menopause. This gender difference could be explained by the action of sex steroids on the lipoprotein profile. In prepubertal children, high-density lipoprotein (HDL) cholesterol and triglyceride levels are similar between sexes, while adult men have generally lower HDL cholesterol and higher triglyceride levels than premenopausal adult women. Most cross-sectional studies have reported that sex hormone binding globulin (SHBG) and testosterone levels correlate positively with HDL cholesterol levels between sexes. Thus SHBG by modulating the balance in the biodisposal of testosterone and estradiol, might have a profound effect on the risk of cardiovascular disease. However, adjustment for body weight and body fat distribution weakens the association between SHBG, testosterone and HDL cholesterol. The negative correlation of fasting insulin with SHBG and HDL cholesterol levels in both sexes, and some evidence that insulin is an inhibitor of SHBG production in vitro, has suggested that hyperinsulinism might negatively regulate SHBG and HDL levels. It remains to be determined whether the inverse relationship between SHBG and insulin levels is coincidental or has a causal effect on the increase of atherosclerosis. Decreased SHBG has been shown to be predictive of the incidence of non-insulin-dependent diabetes mellitus in women but not in men, and of subsequent development of cardiovascular disease and overall mortality in postmenopausal women. SHBG is an index of androgenism in women and of insulin-resistance in both sexes, and might be useful in epidemiological studies of cardiovascular risk. However, in men, SHBG is not predictive of the occurrence of cardiovascular disease. Whether SHBG might have an intrinsic protective effect on the arterial wall through SHBG-receptors is still highly speculative.

Adult↗
PubMed1995

Hormonal substitution in older men.

The biological bases of endocrine alterations in ageing men are now well identified: progressive impairment of testicular function, decline in growth hormone (GH) secretion with decreased insulin-like growth factor-I (IGF-I) levels, and reduced adrenal androgen secretion. Insulin resistance and glucose intolerance also accompany male ageing. The mechanisms of these age-related changes are still unknown. There are preliminary results on the effects of hormonal replacement therapy in older males with mild hypogonadism or decreased IGF-I levels. Controlled placebo studies will in the future define the risks and benefits of long-term administration of androgens, GH or GH-releasing hormone in these patients. In view of the severe potential side effects, the generalized use of hormonal substitution in elderly men cannot, for the moment, be recommended.

Adrenal Glands↗
PubMed1995

Differential effects of insulin and insulin-like growth factor I on the production of plasma steroid-binding globulins by human hepatoblastoma-derived (Hep G2) cells.

Changes in the plasma levels of corticosteroid-binding globulin (CBG) and sex hormone-binding globulin (SHBG) from birth to adulthood suggest that growth factors might influence clearance and/or hepatic secretion of CBG and SHBG in humans. The effects of insulin-like growth factor I (IGF-I) and insulin on CBG and SHBG synthesis by a clone of human hepatoblastoma-derived (Hep G2) cell lines were therefore investigated. The results showed that the immunoconcentrations of CBG and SHBG, as well as total protein concentration in culture medium from Hep G2 cells, were decreased by IGF-I and insulin. However, although the CBG-to-total protein ratio was decreased dose dependently by IGF-I and insulin, IGF-I and insulin did not dose-dependently decrease the SHBG-to-total protein ratio. The steady state levels of CBG and SHBG messenger RNAs (mRNAs) were reduced dose dependently by IGF-I with a half-effect at 5.4 +/- 1.9 and 4.6 +/- 1.6 nmol/L, respectively, and by insulin with a half-effect at 4.3 +/- 1.1 and 4.3 +/- 1.4 nmol/L, respectively. The maximum inhibitory effect of IGF-I on CBG mRNA level was 48 +/- 17% of control values and 60 +/- 13% for SHBG mRNA level. The changes in CBG mRNA levels were quantitatively similar to the changes in CBG immunoconcentration in the Hep G2 medium. In contrast, the inhibitory effects of insulin were only 17 +/- 8% and 31 +/- 12% of control values on CBG and SHBG mRNAs and 37 +/- 4% and 43 +/- 4% on CBG and SHBG concentrations, respectively. These results demonstrate that IGF-I reduces CBG and SHBG production by Hep G2 cells by decreasing mRNA steady state levels. The discrepancy between the inhibitory effects of insulin on CBG and SHBG mRNAs and protein secretion suggests that insulin exercises its inhibitory effects mainly on the mechanism(s) of translation and/or excretion of CBG and SHBG. The respective effects of IGF-I and insulin in the regulation of CBG and SHBG levels during fetal life and pubertal development in humans merit further study.

Carrier Proteins↗
PubMed1995

Effects of diet and metformin administration on sex hormone-binding globulin, androgens, and insulin in hirsute and obese women.

Evidence suggests that hyperinsulinemic insulin resistance may increase serum levels of ovarian androgens and reduce sex hormone-binding globulin (SHBG) levels in humans. The present study was conducted to assess the effect of administration of the biguanide metformin, a drug commonly used in the treatment of diabetes mellitus, on androgen and insulin levels in 24 hirsute patients. The patients selected for the study were obese, with a body mass index higher than 25 kg/m2 and high fasting insulin (> 90 pmol/L) and low SHBG levels (< 30 nmol/L). All patients were given a low calorie diet (1500 Cal/day) and randomized for either metformin administration at a dose of 850 mg or a placebo, twice daily for 4 months, in a double blind study. In the placebo group, diet resulted in a significant decrease in body mass index (30.8 +/- 1.0 vs. 32.7 +/- 1.5 kg/m2; P < 0.0001), fasting insulin (127 +/- 11 vs. 156 +/- 14 pmol/L; P < 0.01), non-SHBG-bound testosterone (0.19 +/- 0.02 vs. 0.28 +/- 0.03 nmol/L; P < 0.02), androstenedione (5.8 +/- 0.5 vs. 9.0 +/- 1.1 nmol/L; P < 0.03), and 3 alpha-diolglucuronide (8.6 +/- 1.1 vs. 11.7 +/- 1.9; P < 0.005) plasma concentrations and a significant increase in the glucose/insulin ratio (0.047 +/- 0.005 vs. 0.035 +/- 0.003; P < 0.001) and plasma concentrations of SHBG (26.0 +/- 3.3 vs. 19.1 +/- 1.9 nmol/L; P < 0.001) and dehydroepiandrosterone sulfate (8.7 +/- 1.5 vs. 8.4 +/- 1.3; P < 0.05). Beneficial effects of diet were not significantly different in the patients who were given metformin instead of placebo. These results confirm that weight loss induced by a low calorie diet is effective in improving hyperinsulinemia and hyperandrogenism in obese and hirsute women. With our study design, metformin administration had no additional benefit over the effect of diet.

Androgens↗
PubMed1994

Androgen suppressive effect of GnRH agonist in ovarian hyperthecosis and virilizing tumours.

OBJECTIVE: Recent studies have suggested that androgen secretion by ovarian virilizing tumours may be gonadotrophin dependent. The aim of this study was to investigate the suppressive effect of GnRH agonist administration on androgen secretion in women with such tumours. DESIGN AND PATIENTS: A single i.m. injection of D-Trp-6-GnRH (GnRHa), 3.75 mg, was given to five unrelated patients referred for clinical symptoms of virilization with plasma testosterone (T) levels greater than 7 nmol/l but with normal dehydroepiandrosterone sulphate (DHEAS) levels. Diagnoses of adrenal tumour or a non-classical 21-hydroxylase deficiency were screened for by the dexamethasone suppression test, ACTH stimulation test and adrenal CT scanning, and were ruled out in all patients. The one premenopausal patient received cyproterone acetate in a dose of 50 mg twice daily for 3 weeks, starting 1 week before GnRHa administration. MEASUREMENT: Testosterone, androstenedione (A), DHEAS, 17-hydroxyprogesterone (OHP), LH and FSH plasma concentrations were measured by radioimmunoassay of blood samples taken before and 3 weeks after GnRHa. RESULTS: In each patient, GnRHa suppressed gonadotrophin levels and reduced T and A to the range for normal control women. With these results, and because accurate localization of an ovarian androgen secreting tumour could not be achieved by pelvic ultrasonography and CT scanning, exploratory laparotomy was undertaken. A Sertoli-Leydig cell tumour was found in the premenopausal patient, and granulosa cell tumour, hilus cell tumour and two hyperthecoses in the four post-menopausal patients. After bilateral ovariectomy and hysterectomy in the post-menopausal woman and after unilateral ovariectomy in the premenopausal women, androgen levels were normalized. CONCLUSIONS: In virilized women, the findings of increased serum testosterone with normal gonadotrophin levels and GnRHa suppression of gonadotrophins leading to normalization of testosterone levels, suggest that various ovarian androgen-secreting tumours, as well as hyperthecosis, are not autonomous but apparently depend upon continuous gonadotrophin stimulation.

17-alpha-Hydroxyprogesterone↗
PubMed1992

[The combined stimulation test sulpiride-TRH in the investigation of prolactin secretion].

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.

Adenoma↗
PubMed1991

Pathophysiology of sex hormone binding globulin (SHBG): relation to insulin.

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.

Adipose Tissue↗
PubMed1991

Glucocorticoid receptors in lymphocytes in anorexia nervosa.

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.

Adolescent↗
PubMed1991

[Inverse relationship between body mass index and fasting insulinemia with testosterone-binding protein in hirsutism].

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.

Androgen-Binding Protein↗
PubMed1991

[Combination of cyproterone acetate and natural estrogens in the treatment of hirsutism].

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.

Adolescent↗
PubMed1990

[Treatment of hirsutism with spironolactone and progestagen combination].

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.

Acne Vulgaris↗
PubMed1990

Rapid escape of cortisol from suppression in response to i.v. dexamethasone in anorexia nervosa.

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.

Administration, Oral↗
PubMed1990

[Hyperandrogenism in premenopausal women].

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)

Adrenal Gland Diseases↗
PubMed1989

[Available anti-androgens for treating skin hyperandrogenism].

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.

Androgen Antagonists↗