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Biomedical subjects

M Pugeat

Publications and source records attributed to M Pugeat.

At least 73 records · Page 4Linked to original sources
PubMed1989

Decreased immunoreactivity and binding activity of corticosteroid-binding globulin in serum in septic shock.

To investigate the mechanism(s) responsible for the depletion of corticosteroid-binding globulin (CBG) activity in serum in septic shock, we developed a radioimmunoassay (RIA) for human CBG, using a monospecific antiserum to human CBG raised in rabbits. CBG was purified from pooled human serum by precipitation with ammonium sulfate and successive affinity chromatography treatments on corticosterone-Sepharose and concanavalin A-Sepharose. Final purification was achieved by HPLC on a diethylaminoethyl-PW (polymer matrix) ion-exchange column. Typical standard curves established for the CBG immunoassay showed parallelism for pure CBG and serial dilutions of sera from patients with septic or nonseptic shock and from healthy controls. Measurements of CBG by RIA showed a significantly (P less than 0.001) lower CBG concentration in patients with septic shock (22.9 +/- 5.9 mg/L, mean +/- SD; n = 23) than in controls (39.9 +/- 6.5 mg/L, n = 21) or in patients with nonseptic shock (33.3 +/- 6.5 mg/L, n = 12). The correlation between the concentrations determined by RIA and the CBG binding capacity was significant (r = 0.619, P less than 0.001, n = 33). The electrophoretic mobility of CBG was similar in sera from septic shock patients and normal subjects (Rf = 0.52-0.56). This suggests that the depletion of the corticosteroid-binding activity in serum during septic shock is associated with a decreased amount of CBG.

Adult↗
PubMed1988

[Acanthosis nigricans, hyperandrogenism, insulin resistance and mixed hyperlipemia].

We report the case of a 22-year old woman who presented skin lesions of acanthosis nigricans, hirsutism and secondary amenorrhoea. She had high plasma levels of adrenal androgens and low plasma levels of sex steroid binding protein. Polycystic ovaries were discovered in the course of a laparotomy performed for paraovarian cyst. An oral glucose tolerance test revealed a state of hyperinsulinism with intolerance to carbohydrates, while the body mass index was normal. This insulin resistant state corresponded in vitro to a decrease in the number of erythrocyte insulin receptors without decrease in their affinity for insulin. Following paradoxical improvement during a full-term pregnancy, there was gradual deterioration of diabetes control requiring insulin therapy. This metabolic decompensation was accompanied by major hyperlipaemia followed by acute haemorrhagic pancreatitis. This case illustrates the course of a type A insulin resistance syndrome which was detected at an early stage in front of an hirsutism-acanthosis nigricans association. The underlying pathogenic mechanisms of these pathologies are discussed.

Acanthosis Nigricans↗
PubMed1988

[Changes in plasma binding protein of sex steroids and transcortin during the treatment of menopause with oral estrogens].

Sex steroid binding protein (SBP) and transcortin (CBG) plasma concentrations were measured in 15 postmenopausal women before and during oral administration of estradiol 2 mg plus estriol 1 mg given alone for one month and in sequential combination with noresthisterone 1 mg for the following months. The results were compared with those obtained in a group of 13 premenopausal women who were studied during the early follicular phase or during administration of estroprogestagens. The oral administration of estrogens slightly increased CBG levels (56.1 +/- 11.4 vs 46.0 +/- 5.2 mg/l, P less than 0.05) which in 4 patient were higher than in premenopausal women. The mean SBP level was lower in postmenopausal women than in premenopausal women (1.02 +/- 0.40 vs 1.35 +/- 0.38 micrograms/dl, P less than 0.02), and SBP correlated negatively and significantly with the body mass index (r = 0.794, P less than 0.02). On average, SBP increased twofold during the estrogen treatment. In 6 patients the concentrations of estrogen-stimulated SBP were higher than the upper limit for premenopausal women. Lowered SBP levels were normalized during estrogen therapy. During estrogen substitution in the postmenopausal women, the mean E2 to SBP ratio (an index of free estradiol) was within the normal limits for premenopausal women. These results demonstrate that SBP is highly sensitive to oral estrogens. The increase in SBP is associated with a free E2 index which is within the physiological range of premenopausal women. The risk(s) or benefit(s) associated with the increase in SBP during estrogen therapy in postmenopausal women deserve to be evaluated by further investigations.

Administration, Oral↗
PubMed1988

Effects of human chorionic gonadotropin, androgens, adrenocorticotropin hormone, dexamethasone and hyperprolactinemia on plasma sex steroid-binding protein.

This presentation reports the effects of androgens, glucocorticoids and some pituitary hormones on plasma sex steroid-binding protein (SBP). The latter was measured by a solid phase method after desteroidation of the plasma. An hCG test (1500 I.U. every other day X 7) was given to 60 boys. In the children with a normal testosterone (T) rise, plasma SBP decreased (% of basal values) either significantly (38.3 +/- 9.3%, group A; n = 29), or moderately (13.4 +/- 4.4%, group B; n = 9) or did not change (-1.6 +/- 6.4%, group C; n = 10). In the 3 infants tested at an age when SBP normally rise sharply, hCG partially prevented this rise. The administration of either fluoxymesterone (10 mg/m2 for 10 days) or depot-T (4 I.M. injections of 100 mg/m2 every 2 weeks) induced a significant drop (about 2-fold) in plasma SBP in a control group of infants or children, but did not change SBP in 3 infants with the androgen insensitivity syndrome. A single injection of 0.25 mg of ACTH did not significantly alter SBP levels. In contrast, at the end of a 3-day ACTH test (0.5 mg/m2 12 hourly X 6) SBP levels had significantly decreased (mean 35% fall) with no age or sex differences, and with no correlation with the cortisol levels reached. However, the lowering effect of ACTH on SBP levels is likely mediated by glucocorticoids, since its effect was reproduced by high doses (8 mg/day for 3 days) of dexamethasone given at once or after 3 days of treatment at lower dose (20 micrograms/kg BW). It would appear that the depressive effect of ACTH and/or dexamethasone is observed for a threshold dose of glucocorticoids (greater than 5-fold physiological levels) and a certain time (greater than or equal to 3 days) of exposure. The mechanism by which androgens and glucocorticoids lower SBP levels in vivo is not yet understood. From recent experiments, showing that both stimulate the secretion of SBP in hepatoma cells in vitro, it would appear that both hormones may alter SBP metabolism. In a selected population of hyperprolactinemic women, with normal weight and no hirsutism, plasma SBP levels were found in the normal female range. The discrepancy with previous studies in the literature may be explained by differences in the degree of hyperprolactinemia and/or associated hyperandrogenim. This study further documents the multifactorial and intricated hormonal influences involved in the regulation of plasma SBP in vivo.

Adrenocorticotropic Hormone↗
PubMed1988

Sex steroid-binding protein in nonendocrine diseases.

In humans, sex steroid-binding protein (SBP) is a protein from the liver which binds with high affinity sex steroid hormones. The plasma concentration of SBP is regulated in part by hormonal factors. It has been shown that estrogens and/or thyroid hormones increase the production of SBP by hepatoma cell lines. It is therefore assumed that the increase in SBP levels in patients given oral estrogens or thyroid hormones is the consequence of a direct stimulation of the liver production of SBP by these hormones. The effects of androgen, progestagen and glucocorticoid hormones are unclear or still a matter of controversy. Moreover, the regulation of the metabolic clearance rate of SBP and the influence of nonhormonal factors on the production of SBP are still speculative. Changes in SBP have been described in a few nonendocrine diseases. A slight hormonal dysfunction may be either the primary or the sole cause of the changes in SBP occurring in these diseases. As an example, elevated SBP levels have been reported in men with liver cirrhosis together with testicular hypofunction and increased estrogen levels. It is therefore difficult to demonstrate that the increase in SBP is due to the liver dysfunction rather than to the endocrinological side effects of cirrhosis. The aim of this review is to present some aspects of the nonhormonal regulation of SBP. There is accumulating evidence in the literature for a relation between SBP levels and body weight and fat distribution, energy balance, diet and physical activity, and lipid metabolism. Therefore, it is tempting to propose that SBP is an index which reflects the status of endocrine, metabolic and nutritional functions. Measurement of SBP may be considered of interest in the light of previous epidemiological studies and the preventive approach to diseases such as hormone dependent tumors, cardiovascular diseases and osteoporosis.

Disease↗
PubMed1988

Lasting remissions in patients treated for Graves' hyperthyroidism with propranolol alone: a pattern of spontaneous evolution of the disease.

Twenty-six patients with Graves' hyperthyroidism treated only with propranolol for 1-21 months have been followed up to 5 years. The patients were evaluated before treatment, at 15, 30, and 90 days during treatment, and then at 90-day intervals during propranolol treatment by clinical examination and measurement of serum free T3, free T4, rT3, TSH, and sex hormone-binding globulin concentrations and serum anti-thyroglobulin, antithyroid microsomal, antithyroid peroxidase, and thyroid-stimulating autoantibodies. Eighteen patients who had no biochemical improvement during propranolol therapy or relapsed after initial improvement were treated conventionally. In contrast, eight patients had a biochemical remission, which has lasted 30-48 months after propranolol withdrawal. The biochemical values before and during treatment did not differ among the two groups of patients, except for the initial serum free T3 levels which were significantly higher in the patients who had no remission. Serum TSH levels returned to normal only in patients who had a long-lasting remission. While thyroid autoantibodies decreased or disappeared during follow-up, the evolution of thyroid-stimulating autoantibody values was grossly related to the clinical outcome. Long-lasting remissions may occur in patients with hyperthyroidism due to Graves' disease not given ablative or antithyroid drug therapy. Since propranolol is devoid of antithyroid and immunosuppressive actions, these remissions are probably spontaneous. Although they tended to occur in patients with less severe disease, no biological parameter was found that predicted the outcome.

Adult↗
PubMed1988

Hyperthyroidism due to selective pituitary resistance to thyroid hormones in a 15-month-old boy: efficacy of D-thyroxine therapy.

A 15-month-old boy had clinical features of hyperthyroidism. In spite of elevated serum thyroid hormone levels (mean serum T4, 230 nmol/L; T3, 4.2 nmol/L), serum TSH levels ranged between 3.3-5.6 mU/L and rose to 35.4 mU/L after TRH stimulation. There was no abnormal serum thyroid hormone binding or any evidence of a pituitary tumor. The boy was treated with carbimazole for 6 months and became euthyroid. However, his thyroid size enlarged, and serum TSH rose to 45 mU/L. In an attempt to suppress TSH secretion, 3,5,3'-triiodothyroacetic acid was added to carbimazole in daily doses from 0.7-1.4 mg. This combined therapy failed to suppress TSH secretion (serum TSH, 10.2 mU/L) and led to recurrence of symptoms of hyperthyroidism. A trial using highly purified dextrothyroxine (contamination by L-T4, 0.05%) as sole therapy then was carried out. Serum TSH levels promptly declined to normal, both basally and after TRH stimulation (basal, 2.4 mU/L; peak, 13.8 mU/L). During a 24-month follow-up period, the boy remained euthyroid. Serum TSH levels remained in the normal range, as did his serum L-T4 levels (93 nmol/L). Complete remission was achieved using a 5-mg daily dose of D-T4. Temporary discontinuation of D-T4 led to prompt relapse of hyperthyroidism. Our patient's TSH hypersecretion appears to be due to selective pituitary resistance to thyroid hormones. Purified D-T4 effectively inhibited TSH secretion in this patient, without inducing significant side-effects, even when the daily dose was high. The cause of partial pituitary unresponsiveness to thyroid hormones is not known. We suggest that transport of thyroid hormones into the thyrotroph cells could be deficient in our patient.

Dextrothyroxine↗
PubMed1988

[Cushing's syndrome caused by ectopic production of CRF by a medullary carcinoma of the thyroid body].

A 58-yr-old man presented a Cushing's syndrome gradually developed for two years, and a cervical tumor. Urinary free cortisol and 17-hydroxy-corticosteroids were elevated and non suppressible under high dose dexamethasone (8 mg a day X 2 days). Plasma calcitonin (7,200 pg/ml), CEA (803 ng/l), beta LPH (624 pg/ml), and CRF (29 pg/ml) were elevated. Total thyroidectomy revealed a medullary carcinoma of the thyroid. Postoperatively the Cushing's syndrome disappeared and plasma CRF became undetectable although plasma calcitonin remained elevated. One out of 3 CRF antisera tested for immunocytology was positive in 10 to 30% of the cells. In tumor extract, CRF (RIA) concentration was 4.75 ng/g. There was no detectable ACTH in the tumor by biochemical as well as immunocytochemical method. In the present report, the next evidences are--for the first time--simultaneously present to demonstrate an ectopic secretion of CRF by a medullary thyroid carcinoma: presence of CRF in systemic blood being undetectable after surgery; cure of the clinical and biological features of Cushing's syndrome after thyroidectomy; characterization of CRF immunoreactivity in tumor. Taken together, the radioimmunological and the immunocytochemical data suggest the production of several molecular forms of CRF.

Carcinoma↗
PubMed1987

Effects of drug administration on gonadotropins, sex steroid hormones and binding proteins in humans.

The possible mechanisms by which the administration of drugs may alter the gonadal function in humans are considered in this review. Based on personal data, and on data published in the literature, the following events may occur: (1) blockade of gonadal steroidogenesis; (2) interaction of drug(s) with the steroid-binding protein system in plasma, and (3) interference of drug(s) at the level of the feedback control of gonadotropin secretion. Representative examples of the above mechanisms are as following: (1) Ketoconazole possesses inhibitory effects in vitro on cytochrome P-450. When given in adult males, it decreased the plasma concentrations of testosterone (T) and androstenedione and increased 17 alpha-hydroxyprogesterone levels, suggesting that this drug acts in vivo on gonadal steroidogenesis by blocking the 17,20-lyase. (2) Danazol is a progestagen with high affinity for sex steroid-binding protein (SBP); when given in high dosages in normal males, it increased rapidly the dialyzable fraction (percent protein unbound or free fraction) of T. This suggests that by interacting with the binding sites of SBP, danazol and/or its metabolites displace the fraction of T bound to SBP. However, in males as well as in females, the long-term administration of danazol decreased also the binding capacity of SBP, and consequently increased the free fraction of sex steroid hormones. (3) Dihydrotestosterone (DHT), the most active androgen in many target cells, given at therapeutic dosages to adult males, resulted in a decrease in plasma concentrations of luteinizing hormone (LH) and T, without any significant change in the percent of free T, even though the affinity of DHT for SBP is higher than that of T. This suggests that the main effect of DHT is to inhibit gonadotropin secretion at the central level. (4) Flutamide, a nonsteroidal antiandrogen, increased both LH and T levels, demonstrating its pure antiandrogenic activity on gonadotropin secretion. The consequence(s) of the effects of such drugs on the production, the metabolic clearance rate and the bioavailability of sex steroid hormones are discussed.

Androgens↗
PubMed1987

[TeBG and thyrotoxicosis in the hot thyroid nodule].

The binding capacity of serum TeBG (testosterone-estradiol binding globulin), the plasma concentrations of thyroid hormones and the TSH response to TRF (200 micrograms i.v.) have been measured in female patients with a solitary autonomously functioning thyroid nodule (n = 26) or with a cold thyroid nodule (n = 20). It was found that TeBG was higher than the upper limit for normal (1.77 micrograms/dl) in the patients (n = 10) with increased serum concentrations of thyroid hormones and in 5 patients among 16 with normal thyroid hormone levels. After surgical removal of the nodule, the increased TeBG levels fell down within the normal, while the response of TSH to TRF which was suppressed before surgery, was recovered. In patients with a cold nodule, the administration of dl-Thyroxine (200-300 micrograms/daily) suppressed the response of TSH to TRF and increased slightly TeBG from 0.97 +/- 0.08 to 1.29 +/- 0.10 micrograms/dl (p less than 0.05) with a value higher than 1.77 micrograms/dl in 5. These data suggested that the pituitary secretion of TSH and the liver production of TeBG have a different threshold of sensitivity to thyroid hormones action. It is proposed that the measure of TeBG is a tool for the diagnosis of thyrotoxicosis in patients with autonomous thyroid nodules.

Adenoma↗
PubMed1986

[Testicular function during prolonged corticotherapy].

Prolonged corticosteroid therapy produces a major degree of protein catabolism. Short-term treatment with ACTH or glucocorticoids results, in males, in a fall in plasma testosterone levels. In order to determine the origin of this hypogonadism, the testicular function was investigated in 18 men under prolonged glucocorticoid treatment. The mean plasma testosterone level in men treated for less than 3 months (5.9 +/- 0.8 ng/ml) was not statistically different from that obtained in controls (7.5 +/- 0.5 ng/ml; P greater than 0.05). However, the mean plasma luteinizing hormone level was significantly higher in these patients than in controls (8.2 +/- 1.9 mUl/ml vs 3.6 +/- mUl/ml respectively; P less than 0.001). In patients treated for more than 2 years, the mean plasma testosterone level (3.8 +/- 0.6 ng/ml) was significantly lower than in controls (P less than 0.001), but the mean plasma luteinizing hormone level was normal (5 +/- 1 mUl/ml). Plasma testosterone levels are negatively correlated with the daily dose of glucocorticoid (r = -0.81; P less than 0.001). The free testosterone index was within normal range in 5 of the 9 men under prolonged steroid therapy, near the lower limit of normality in 2 men and definitely low in 2 other men. The gonadotrophin response to the luteinizing hormone releasing hormone was normal, whereas the testicular response to human chorionic gonadotrophin was reduced. These data suggest that prolonged treatment with steroidal anti-inflammatory agents influences both gonadotrophic and testicular function and may be associated with true hypoandrogenism.

Adrenal Cortex Hormones↗
PubMed1986

Sex hormone binding globulin in women with anorexia nervosa.

In 29 women with anorexia nervosa, on a blood sample withdrawn at 0900 h before and during weight gain, the binding parameters of serum sex hormone binding globulin (SHBG) were measured by a solid phase method and the levels of testosterone, oestradiol and thyroid hormones were measured by radioimmunoassay. The binding capacity of SHBG was higher than the upper limit for normally menstruating women in 23 patients whilst its affinity for binding testosterone at 37 degrees C was normal (0.32-0.53 X 10(-9) mol/l). The mean levels of testosterone, oestradiol and free thyroxine were normal and the mean level of triiodothyronine was significantly (P less than 0.005) decreased. The binding capacity of SHBG did not correlate significantly with body mass index, percent weight lost, thyroid hormone or sex hormone levels. In 9 patients, an i.v. infusion providing 1200-1400 calories daily was given for 1 week. In these patients a significant decrease (P less than 0.005) in the binding capacity of SHBG (from 74.7 +/- 26.7 to 52.9 +/- 21.8 nmol/l) and a significant increase (P less than 0.001) in T3 levels (from 0.69 +/- 0.21 to 0.95 +/- 0.13 nmol/l) was observed. In 14 patients, when a weight gain of at least 5% was obtained, the binding capacity of SHBG fell into the normal range (25.6-62.9 nmol/l) while T3 levels rose to normal (0.85-2.30 nmol/l). These findings suggested that variations of calorie intake and/or body weight may influence the binding capacity of SHBG in the human.

Adolescent↗
PubMed1986

[Morphologic and functional study of a human insulin-secreting cell line].

Monolayer cell cultures were obtained from a human insulinoma (HIN) after collagenase digestion. HIN cells were initially plated on extracellular matrix (ECM) secreted by bovine corneal endothelial cells. Capsular integrity from cell clusters quickly interrupted and cell began to migrate as adhesive sheets onto ECM. After 2 months on ECM cell attachment and proliferation occurred on plastic allowing cloning of cells by limiting dilution. 9 clones were successfully cultured for 7 months with 20 subsequent passages. Immunoreactivity for insulin by indirect immunofluorescence typical secretory granules by electron microscopy and stable amounts of immunoreactive insulin in culture media suggest that HIN cells are beta cell related. One clone HIN D8 when challenged for half an hour with either 30 mM glucose, 1 mM isobutyl Methylxanthine 4 mM Tolbutamide, 10(-6) M glucagon responded respectively with a 1.5, 2, 3 and 1.5 fold increase in insulin output. Population doubling time of HIN D8 was 42 hrs. Establishment of such insulin secreting cell lines provides a valuable tool for diabetes research.

Adenoma, Islet Cell↗
PubMed1985

Althesin interaction with human plasma steroid binding globulins.

The binding affinities of two steroid anaesthetics, alphaxalone (Alfx) and alphadolone acetate (Alfd), for testosterone-oestradiol-binding globulin (TeBG) and corticosteroid-binding globulin (CBG) were measured in human serum. In 8 male patients, the effect of i.v. administration of Althesin (a mixture of Alfx and Alfd) on the transport of testosterone (T) and cortisol (F) was studied. Both Alfx and Alfd bind to TeBG and CBG with a relatively high affinity (10(6)M-1). A significant change in the percentage of unbound T was observed during Althesin infusion, with no change in total T concentration or in the TeBG binding parameters. The results suggest that by interaction with TeBG binding sites Alfx and/or Alfd displaced T bound to TeBG, and transiently increased the percentage of unbound T. A significant increase in the concentration of F was observed during althesin infusion, while the percentage of unbound F and the CBG binding parameters were unchanged. The dose of Alfx and Alfd used was not sufficient to alter the transport of F during brief althesin anaesthesia in men.

Adolescent↗
PubMed1985

Beta-lipotropin and cortisol responses to an intravenous infusion dexamethasone suppression test in Cushing's syndrome and obesity.

An i.v. infusion dexamethasone (Dex) test was used to investigate the ACTH feedback response in 9 normal subjects, 12 obese patients, and 11 patients with Cushing's syndrome. Dex phosphate was infused iv for 4 h, starting at 1100 h (1 mg/h). Plasma concentrations of beta-lipotropin (beta LPH) and cortisol were measured every 20 min between 0900 and 1600 h, then every 2 h until midnight and at 0900 h the next day. In normal subjects and obese patients, plasma beta LPH and cortisol concentrations fell rapidly to less than 40 ng/liter and 3 micrograms/dl, respectively, at the end of Dex infusion. Subsequent values remained low through 0900 h the next day. In 7 patients with Cushing's disease, basal plasma beta LPH and cortisol concentrations declined by greater than 50% during the Dex infusion. In these patients, rapid escape from suppression occurred between 1600 and 2400 h; by 0900 h the following day, beta LPH and cortisol levels were higher than 100 ng/liter and 10 micrograms/dl, respectively. In 3 patients with adrenal tumors, beta LPH concentrations were low, and cortisol concentrations did not decline during the Dex infusion. In 1 patient with ectopic ACTH secretion, beta LPH concentrations were high and were not suppressed by the Dex infusion. We conclude that the iv infusion Dex suppression test can distinguish patients with Cushing's syndrome from normal or obese subjects and can aid in the etiological diagnosis of Cushing's syndrome.

Adult↗
PubMed1984

Plasma testosterone transport in primates.

All primate species, including Old and New World primates and prosimians have a plasma testosterone-estradiol binding globulin (TeBG), which is a glycoprotein and has a similar mobility in polyacrylamide gel electrophoresis. In New World primates the TeBG binding capacity for [3H]testosterone was higher and its affinity lower than in Old World primates. These changes were associated with high unbound plasma testosterone concentrations in these species. Binding parameters of TeBG in prosimian species varied markedly. Thus, in primate evolution TeBG was conserved despite marked differences in binding characteristics. In New World primates changes are associated with high total and unbound testosterone, a finding concordant with alterations of other steroid hormones concentration in these species with "generalized steroid hormone resistance".

Animals↗
PubMed1984

Increased plasma concentration of N-terminal beta-lipotrophin and unbound cortisol during pregnancy.

The plasma concentration of N-terminal beta-lipotrophin (beta-LPH), total and protein unbound cortisol, progesterone and the transcortin (CBG) binding parameters have been measured in 21 women in the early follicular phase and in 70 pregnant women at various stages of pregnancy. Results showed that the plasma CBG binding capacity and the concentrations of total cortisol and progesterone increased significantly at each trimester of pregnancy while the plasma concentration of unbound cortisol increased significantly only in the 2nd and the 3rd trimesters of pregnancy. In addition, a significant increase of N-terminal beta-LPH level was observed during the 3rd trimester. By chromatography, it is demonstrated that during the 3rd trimester of pregnancy the beta-LPH/gamma-LPH molar ratio decreases dramatically and that the increase of N-terminal beta-LPH concentration is mainly due to a two fold increase in gamma-LPH concentration.

Female↗