RESUMO
A 41-years old male with short stature, abnormal male sex differentiation, aspermia and schizoid character disorder is described. The patient was studied from clinical, endocrinological and genetic perspectives. Cytogenetical analysis revealed a chromosomic mosaicism formed by two normal lines 45X and 46,XY qh-. Molecular studies on AZF region evidenced that it was conserved. The correlation of the symptoms with the cytogenetic finding is discussed.
Assuntos
Aspermia/genética , Cromossomos Humanos X , Cromossomos Humanos Y , Mosaicismo , Esquizofrenia/genética , Adulto , Aspermia/complicações , Humanos , Cariotipagem , Masculino , Esquizofrenia/complicações , Aberrações dos Cromossomos SexuaisRESUMO
Ketoconazole is an imidazole derivative used as an antimycotic agent with reported effects on the endocrine system, but very little is known about its possible actions on thyroid function. Our purpose was to study the influence of this substance on the basal and TSH-stimulated iodide uptake in the rat thyroid cell strain FRTL-5. Ketoconazole (1-50 mumol/l) was shown to slightly increase the basal iodide uptake but, at higher concentrations (75-100 mumol/l), it sharply decreased iodide uptake below the basal levels. When the cells were cultured under bTSH stimulation (30 UI/l), the inhibitory effect of ketoconazole was exerted at concentrations as low as 25 mumol/l. This inhibition was observed even if it was added to the culture medium immediately before the Na125I addition. Forskolin, a stimulator of adenylate cyclase activity, was unable to prevent the iodide uptake inhibition. Low doses of ketoconazole increased cAMP concentrations. In the presence of TSH this effect was more evident in an inverse dose-dependent way. Because of its dual action, it can be assumed that ketoconazole could influence the iodide uptake in the FRTL-5 cells through more than one mechanism.
Assuntos
Iodetos/farmacocinética , Cetoconazol/farmacologia , Glândula Tireoide/metabolismo , Animais , Bovinos , Linhagem Celular , Colforsina/farmacologia , AMP Cíclico/metabolismo , Ratos , Glândula Tireoide/citologia , Tireotropina/antagonistas & inibidores , Tireotropina/metabolismo , Tireotropina/farmacologiaRESUMO
UNLABELLED: We determined glucocorticoid receptors in human mononuclear leukocytes in 9 patients with Cushing's disease, in order to correlate them with laboratory data. Receptors were measured by a whole-cell assay method, after incubation with [3H]-dexamethasone in the presence or absence of excess unlabelled hormone. In Cushing's disease, there were 4425 +/- 364 sites/cell (N = 9), similar to in the controls: 4473 +/- 476 (N = 10); average Kd was 2.42 +/- 0.52 nmol/l (N = 3) similar to in the controls: 2.0 +/- 0.20 nmol/l (N = 3). In Cushing's patients we found significant negative correlations between basal glucocorticoid receptors and: 1) morning blood cortisol (r = -0.67, P less than 0.05), and 2) 17-ketogenic steroids after 2 mg of dexamethasone (r = -0.85, P less than 0.01). No correlations were observed with afternoon blood cortisol, free urinary cortisol, basal and post-8-mg dexamethasone 17-ketogenic steroids, TRH-TSH area, urinary calcium, plasma glucose, or systolic blood pressure. CONCLUSIONS: In Cushing's disease, a subtle receptor down-regulation may exist, as suggested by the inverse relationship between glucocorticoid receptors and morning blood cortisol. Secondly, the relationship between basal receptors and 17-ketogenic steroids after 2 mg of dexamethasone suggests that glucocorticoid receptors in human mononuclear leukocytes could reflect the sensitivity of the nervous system-pituitary-adrenal axis to dexamethasone inhibition.