Search PubMed⌕ Search

Biomedical subjects

M Pugeat

Publications and source records attributed to M Pugeat.

At least 91 records · Page 5Linked to original sources
PubMed1984

Acute dopaminergic blockade by sulpiride stimulates beta-endorphin secretion in pregnant women.

The pars intermedia of the pituitary gland is well developed in most animal species but rudimentary in adult human subjects. Unlike the anterior pituitary, the intermediate lobe metabolizes proopiomelanocorticotrophin (POMC) mainly to beta-endorphin and to alpha-melanotrophin (alpha-MSH). This activity of the pars intermedia is under an inhibitory dopaminergic control. Biochemical and immunohistochemical evidence suggests the hyperplasia of the intermediate lobe during human pregnancy. The present study demonstrates that an acute dopaminergic blockade by sulpiride dramatically increases plasma concentrations of beta-endorphin in pregnant women but not in non-pregnant women providing functional evidence for the intermediate lobe hypothesis.

Adult↗
PubMed1984

Demonstration of an antiglucocorticoid action of progesterone on the corticosterone inhibition of beta-endorphin release by rat anterior pituitary in primary culture.

The effects of progesterone or 17 alpha-hydroxyprogesterone on corticosterone regulation of beta-endorphin (beta-end) release have been studied in vitro using primary culture of rat anterior pituitaries. Incubation of pituitary cells with ovine corticotropin-releasing factor (CRF) for 2 h resulted in a dose-dependent increase in beta-end release. Maximal stimulation was obtained with 200 ng/ml CRF. Preincubation for 2 h with corticosterone resulted in a dose-dependent inhibition of CRF-induced beta-end release. When the cultures were preincubated for 2 h with 200 ng/ml corticosterone and increasing concentrations (1, 10, 100, 1,000, and 10,000 ng/ml) of progesterone, a significant decrease in the corticosterone feedback action was observed with 100 ng/ml progesterone. Complete inhibition of the action of 200 ng/ml corticosterone was achieved with 10,000 ng/ml progesterone. Moreover, when the cultures were preincubated with increasing concentrations of corticosterone in the presence of 100 ng/ml progesterone, the ED50 of corticosterone increased significantly from 212 +/- 36 to 940 +/- 42 ng/ml (mean +/- SEM; P less than 0.01). Under the same conditions, 17 alpha-hydroxyprogesterone had no effect. These data demonstrate that progesterone antagonizes the corticosterone feedback inhibition of beta-end release by rat anterior pituitary.

Animals↗
PubMed1984

Effects of 10 days administration of percutaneous dihydrotestosterone on the pituitary-testicular axis in normal men.

Dihydrotestosterone (DHT) was administered percutaneously in a dose of 125 mg twice daily for 10 days to 12 normal men. Basal plasma levels of testosterone (T), 17 beta-estradiol (E2), and LH were measured every 2 days in these men and every 5 days in subjects from a control group receiving placebo. The daytime course of plasma hormone levels between two DHT applications was studied in six men. LRH tests were performed in nine men before and on day 10 of DHT administration. Plasma levels of free T and free E2, and T - E-binding globulin capacity and affinity were measured in six men before and on days 5 and 10 of DHT administration. Before DHT administration, there was no difference in basal plasma levels of T, DHT, E2, and LH between the control and the DHT-treated group. In the latter group, plasma DHT levels increased sharply from 0.52 +/- (+/- SE) to 3.70 +/- 0.92 ng/ml on day 2 (P less than 0.001) during DHT treatment. Plasma T, E2, and LH levels decreased significantly from 7.33 +/- 0.74 to 1.33 +/- 0.54 ng/ml (P less than 0.001), from 46 +/- 5 to 20 +/- 3 pg/ml (P less than 0.01), and from 7.8 +/- 1 to 4.2 mIU/ml (P less than 0.05), respectively. Except for a small decrease in plasma DHT (P less than 0.05) 12 h after the previous DHT application, hormone levels were stable during the time between the two DHT treatments. The responses of LH and FSH to LRH were not different before and on day 10 of DHT administration. Plasma levels of free T and free E2 as well as those of total T and E2 decreased; however, the percentages of unbound T and E2 were not different before and during DHT administration. T - E-binding globulin capacity and affinity were not modified by DHT administration. Changes in plasma DHT levels were negatively correlated with those in The results of this study demonstrate that 10-days DHT administration has an inhibitory effect on the hypothalamo-pituitary-testicular axis in normal men.

Adult↗
PubMed1984

The value of beta-lipotrophin measurement during the short metyrapone test in patients with pituitary diseases and in Cushing's syndrome.

Serum 11-deoxycortisol (S) determination has been used to evaluate the pituitary adrenal response to the short metyrapone (MTP) test. The validity of this indirect evaluation of corticotrophin ACTH reserve has been questioned since the MTP-induced S elevation may reflect a passive accumulation rather than an ACTH activated adrenal response. The purpose of this study was to evaluate the usefulness of serum beta-lipotrophin (beta-LPH) measurement during the short midnight MTP test (30 mg/kg body weight) in patients with pituitary diseases (n = 36) and in patients with Cushing's syndrome (n = 8). In 28/36 patients with pituitary diseases both S and beta-LPH concentrations were increased normally by MTP. In 8/36 patients the beta-LPH response was lacking, while their serum S concentrations increased significantly. The absence of beta-LPH response to MTP in these 8 patients was in good agreement with the diagnosis of ACTH insufficiency because in 7 of them the cortisol response to insulin induced hypoglycaemia was also insufficient. In the 8 patients with Cushing's syndrome serum S concentration increased following MTP administration in all the cases. In 2 with adrenal adenoma the increase of S level was an ACTH-independent phenomenon, since beta-LPH level was undetectable both before and after MTP administration. In 2 patients with ectopic ACTH secretion, the basal beta-LPH concentrations were high and remained unmodified by MTP administration. In the 4 patients with Cushing's disease, MTP administration resulted in a dramatic increase of beta-LPH concentration. We conclude that beta-LPH measurement improves the utility of the short MTP test for investigation of pituitary adrenal function.

Adrenocorticotropic Hormone↗
PubMed1984

[Polycystic ovaries. Round table].

Because of the variety and inconstancy of the clinical symptoms, it is difficult to establish a classification of the clinical forms. However, the laboratory profile, essentially a raised serum LH, is fairly constant in every case. The pathophysiology of the disequilibrium of androgen and gonadotrophin secretion can be explained on the basis of various initial functional abnormalities, such as an excess of adrenal androgens or LH or, conversely, a deficiency of FSH. Cystic disease is very common in veterinary medicine and presents a number of specific features. The treatment of polycystic ovaries depends on the symptoms (hirsutism, amenorrhea, sterility). In the case of sterility, inducers of ovulation are effective, but are very difficult to manipulate. A number of authors propose surgical excision (removal of the larger of the two ovaries).

Adrenal Cortex Hormones↗
PubMed1983

Unresponsiveness of prolactin to repeated injection of sulpiride in man.

The prolactin (PRL) response to repeated injections of sulpiride, a dopamine antagonist, was evaluated in 18 healthy young men. Each subject received one or two injections of sulpiride 1 mg/kg i.m. The first injection was always given at 9 a.m. and the second after 2, 8, 24 or 48 h. Blood samples were taken through an indwelling venous catheter every 20 min during the first hour following the injection and then hourly for 12 h. The first sulpiride injection increased serum PRL level 10-fold the peak being reached after 20 or 40 min. The second injection up to 24 h had no effect on serum PRL, but when two sulpiride injections were given at a 48 h-interval, both caused a sharp increase in PRL. To conclude, PRL cells in man, after a sulpiride injection, may therefore be unresponsive to a second sulpiride injection for more than 24 h.

Adult↗
PubMed1983

Strategic approach of hyperandrogenism in women.

Based on the results of the laboratory screening of 35 hirsute patients, a strategic approach of hyperandrogenism is proposed. The determination of plasma concentration of total testosterone (T), androstenedione (A) and dehydroepiandrosterone sulfate (DHEAS) appeared to be the basic investigation before to further explore the adrenal (ACTH test) and/or ovarian (gonadotropin measurements) androgen secretion. Together with the clinical findings, plasma T, A and DHEAS levels generally bring evidence of androgen-secreting tumors or polycystic ovaries, or suggest the possibility of adrenal hyperplasia. In the other cases, only the determination of plasma unbound T level is useful for demonstrating the hyperandrogenism. Finally in patients with 'so-called' idiopathic hirsutism, while evidence of excessive androgen production can be obtained by the laboratory screening, the origin of this hyperandrogenism remains uncertain in most cases.

Adrenocorticotropic Hormone↗
PubMed1982

[Plasma androgens and testosterone binding globulin levels in hirsute women. Effects of dexamethasone and oestrogen-progestagen administration (author's transl)].

In a group of 19 women with idiopathic hirsutism plasma levels of testosterone binding globulin were significantly lowered, and plasma levels of total and unbound testosterone were significantly raised. After administration of dexamethasone or oestrogenprogestagen combination, the concentrations of free testosterone returned to the normal range for non hirsute women. This suggests that both the ovary and the adrenal cortex were responsible for the high plasma testosterone levels observed in these patients.

Adolescent↗
PubMed1982

Glucocorticoid hormone resistance during primate evolution: receptor-mediated mechanisms.

The concentrations of total and protein-unbound plasma cortisol of New World monkeys are higher than those of Old World primates and prosimians. The urinary free-cortisol excretion also is increased markedly. However, there is no physiologic evidence of increased cortisol effect. These findings suggest end-organ resistance to glucocorticoids. This was confirmed by showing that the hypothalamic-pituitary adrenal axis is resistant to suppression by dexamethasone. To study this phenomenon, glucocorticoid receptors were examined in circulating mononuclear leukocytes and cultured skin fibroblasts from both New and Old World species. The receptor content is the same in all species, but the New World monkeys have a markedly decreased binding affinity for dexamethasone. Thus, the resistance of these species to the action of cortisol is due to the decreased binding affinity of the glucocorticoid receptor. This presumed mutation must have occurred after the bifurcation of Old and New World primates (approximately 60 x 10(6) yr ago) and before the diversion of the New World primates from each other (approximately 15 x 10(6) yr ago).

Animals↗
PubMed1982

Primary cortisol resistance in man. A glucocorticoid receptor-mediated disease.

We have studied a man suspected of having primary cortisol resistance on the basis of high 24-h mean plasma cortisol levels (27.4 micrograms/dl) and no stigmata of Cushing's syndrome. His son had slightly elevated 24-h mean plasma cortisol levels (9.9 micrograms/dl; normal 7.52 micrograms/dl). Both had high plasma protein unbound cortisol and increased urinary free cortisol. Plasma ACTH concentration was high, and both were resistant to adrenal suppression by dexamethasone. The father appeared to have mineralocorticoid excess resulting in hypertension, hypokalemia, and metabolic alkalosis. This was found to be due to markedly elevated plasma levels of deoxycorticosterone and corticosterone. The son, who was normotensive, had mildly increased plasma corticosterone and normal deoxycorticosterone levels. To study the apparent end-organ resistance to cortisol, we examined the glucocorticoid receptor in the white cells and fibroblasts of these patients. In both tissues, using both whole cell and cytosol assays, the glucocorticoid receptor was found to have reduced affinity for dexamethasone. In the cytoxol assays, a reduced receptor number was found as well. We conclude that cortisol resistance is a rare familial syndrome owing to an abnormal glucocorticoid receptor with a decreased affinity for cortisol.

Adrenocortical Hyperfunction↗
PubMed1982

Regulation of the pituitary-adrenal axis and corticosteroid-binding globulin-cortisol interaction in the guinea pig.

Adult male guinea pigs were used to examine pituitary-adrenal function and corticosteroid-binding globulin (CBG)-cortisol interaction. A biphasic pattern in the circadian rhythm of plasma cortisol was observed, with nadirs occurring at 0800 and 2400 h and peaks and 1600 and 0400 h. An excellent correlation was noted between total and free plasma cortisol levels. In contrast, no correlation was noted between CBG binding capacity and either the total or free plasma cortisol level. The free plasma cortisol concentration ranged from 0.6-5.8 micrograms/dl, representing 6.1-14.5% of the total cortisol concentration. The CBG binding capacity ranged from 12.2-161.7 micrograms/dl, and the binding affinity was 1.3-2.2 x 10(7) M-1 at 22 C, which is 20-fold lower than that of human CBG. These results suggest that CBG in the guinea pig has a relatively minor effect on the plasma distribution of cortisol, and that free plasma cortisol is dependent on cortisol binding to nonspecific plasma proteins as well as on the total plasma cortisol concentration. It was found that the guinea pig was relatively resistant to dexamethasone suppression, requiring at least 1 mg/kg BW to obtain essentially complete suppression of the pituitary-adrenal axis. In addition, it was found that administering dexamethasone 6 h before the time that the animals were killed led to suppression, whereas giving the steroid 12 h before killing the animals was totally ineffective. Stress induced by both ether vapor and histamine injection significantly increased plasma cortisol levels. When the guinea pigs were treated with a 1 mg/kg BW dose of dexamethasone 6 h before the stimulus, however, a marked suppression of the plasma cortisol increment secondary to application of the stressful stimulus occurred.

Animals↗
PubMed1982

Evidence of excessive androgen secretion by both the ovary and the adrenal in patients with idiopathic hirsutism.

Fifteen patients with idiopathic hirsutism, who had no attenuated adrenal hyperplasia, obesity, enlarged ovaries, or amenorrhea, were studied. Excessive androgen secretion by adrenal tissue was suggested by the finding of increased levels of dehydroepiandrosterone sulfate, which decreased after dexamethasone administration but did not change after human chorionic gonadotropin (hCG) injection. Excessive androgen secretion by ovarian tissue was suggested by the finding that testosterone and androstenedione levels were elevated, correlated significantly with the levels of luteinizing hormone, decreased with administration of estrogen-progestagen, and increased after hCG injection. Notably, free testosterone levels, which were significantly increased, were only partially suppressed during dexamethasone or estrogen-progestagen administration. These results provide further evidence that both the adrenals and the ovaries secrete androgens excessively in patients with idiopathic hirsutism.

Adrenal Glands↗
PubMed1979

[A feminizing adrenal carcinoma in man: in vivo and in vitro study (author's transl)].

A 31 years old man with an adrenocortical carcinoma was studied. Clinically he had a bilateral and recidiving gynecomastia and showed high urinary oestrogens, 17 cetosteroids, tetra-hydro-desoxy-cortisol and pregnandiol excretion with normal cortisol production. A partial increase on ACTH, no suppression on dexamethasone and no variation on HCG administration were observed. The surgical resection of the tumor normalized this urinary excretion. The serum dehydro-epiandrosterone (DHEA) and sulfate (DHEAS), oestrone, oestradiol, androstenedione (A) levels were greatly elevated. No variations of the cortisol, A, DHEA and DHEAS was noted after ACTH injection. In vitro the lack of ACTH's action was related to an anomaly of ACTH receptor with normal protein kinase activity.

17-Ketosteroids↗
PubMed1977

[Effects of clomiphene and estrogens on circulating gonadotropins, testosterone, androstenedione, in old menopausal women (author's transl)].

The threshold of sensitivity of the gonadostat has been tested in 20 old menopausal women by clomiphene (50 or 200 mg/day for 5 days) and/or low doses of ethinyl oestradiol (EE2) (10 or 20 microgram/day). Clomiphene did not increase nor decreased serum levels of LH-FSH and testosterone (T) but increased significantly androstenedione (A) levels. Even at the lower dosage used, EE2 decreased drastically the levels of LH but less completely that of FSH. Clomiphene breaks off partially the oestrogen's blockade on FSH but not on LH. No modification was observed for T and A even after 30 days of estrogen therapy. This data shows the peculiar sensitivity of the gonadostat in advanced menopaused women. It also suggests that the gonadostat exhibits a low threshold of sensitivity analogous to that observed in late prepubertal period. Moreover, the different behaviour of LH and FSH in response to the negative feedback of oestrogens supports that an ovarian factor, distinct from estrogens and missing during menopause plays a role in the regulation of FSH.

Clomiphene↗
PubMed1977

[Plasma LH response to LHRH in hypothyroid and thyroxin-treated rats (author's transl)].

Plasma LH response after intravenous injection of synthetic LHRH (50 ng) was studied in male rats (normal, after thyroidectomy, after treatment by dl thyroxin 50 microgram/a day, 10 days). LH response was significantly elevated in hypothyroid animals although it was not influenced by thyroxin injections. Prolonged plasma LH half-life in hypothyroid rats can account in this result.

Animals↗