Independent and overlapping effects of corticosterone and testosterone on corticotropin-releasing hormone and arginine vasopressin mRNA expression in the paraventricular nucleus of the hypothalamus and stress-induced adrenocorticotropic hormone release.
(17/1561)
Adrenocorticotropin (ACTH) release is regulated by both glucocorticoids and androgens; however, the precise interactions are unclear. We have controlled circulating corticosterone (B) and testosterone (T) by adrenalectomy (ADX) +/- B replacement and gonadectomy (GDX) +/- T replacement, comparing these to sham-operated groups. We hoped to reveal how and where these neuroendocrine systems interact to affect resting and stress-induced ACTH secretion. ADX responses. In gonadal-intact rats, ADX increased corticotropin-releasing factor (CRH) and vasopressin (AVP) mRNA in hypothalamic parvocellular paraventricular nuclei (PVN) and ACTH in pituitary and plasma. B restored these toward normal. GDX blocked the increase in AVP but not CRH mRNA and reduced plasma, but not pituitary ACTH in ADX rats. GDX+T restored increased AVP mRNA in ADX rats, although plasma ACTH remained decreased. Stress responses. Restraint-induced ACTH responses were elevated in ADX gonadally intact rats, and B reduced these toward normal. GDX in adrenal-intact and ADX+B rats increased ACTH responses. Without B, T did not affect ACTH; together with B, T restored ACTH responses to normal. The magnitude of ACTH responses to stress was paralleled by similar effects on the number of c-fos staining neurons in the hypophysiotropic PVN. We conclude that gonadal regulation of ACTH responses to ADX is determined by T dependent effects on AVP biosynthesis, whereas CRH biosynthesis is B-dependent. Stress-induced ACTH release is not explained by B and T interactions at the PVN, but is determined by B- and T-dependent changes in drive to PVN motorneurons. (+info)
Renal excretion of monovalent cations during functional adrenalectomy in conscious sheep.
(18/1561)
In sheep with both adrenals removed and one re-implanted in the neck, functional adrenalectomy was produced in conscious undisturbed animals by occluding the blood supply to the transplanted gland. Functional adrenalectomy caused a fall in potassium excretion and a very large increase in sodium excretion and was reversed by aldosterone. Hydrocortisone infusions slightly increased potassium excretion and reduced solute-free water reabsorption. Preliminary evidence suggests that potassium secretion into urine was still occurring during the 8 hr period of adrenal occlusion and functional adrenalectomy. (+info)
A case of extraadrenal pheochromocytoma associated with adrenal cortical nodular hyperplasia and papillary thyroid carcinoma.
(19/1561)
A 64-year-old woman was admitted in November, 1996 for fluctuating blood pressure. There was multinodular goiter in her neck. High urine VMA and serum aldosterone were noted. Computed tomography showed an oval lesion in the left adrenal gland. Left adrenalectomy was performed and the pathology was proved to be adrenal cortical nodular hyperplasia. Fluctuating blood pressure and high urine VMA persisted after the operation. CT scan of the abdomen revealed a soft tissue mass in lower abdomen. The patient was admitted again in September, 1997. Laboratory examinations showed normal serum aldosterone, normal plasma renin activity and high urine VMA. Aspiration cytology of the thyroid gland disclosed papillary thyroid carcinoma. [131I]-metaiodobenzylguanidine image revealed a high uptake lesion in the right L-3 paravertebral area. Tumor excision and thyroidectomy were performed. The pathology was reported as extraadrenal pheochromocytoma and papillary thyroid carcinoma. Papillary thyroid carcinoma is rarely associated with pheochromocytoma. To our knowledge, this paper is the first report of a patient with extraadrenal pheochromocytoma associated with papillary thyroid carcinoma and adrenal cortical nodular hyperplasia. (+info)
A patient with preclinical Cushing's syndrome and excessive DHEA-S secretion having unilateral adrenal carcinoma and contralateral adenoma.
(20/1561)
We report a case of preclinical Cushing's syndrome in a 54-year-old male associated with bilateral adrenocortical tumours. Physical findings and general laboratory data were unremarkable except for mild hypertension (158/90 mmHg) and impaired glucose tolerance. Endocrinological evaluation revealed the presence of autonomous cortisol secretion including unsuppressible serum cortisol by 8 mg dexamethasone test (11 microg/dl), high serum DHEA-S (3580 ng/ml, normal: 400-3500) and increased urinary 17-KS excretion (31.0-35.8 mg/day, normal: 5.8-21.3). CT scan demonstrated the presence of tumours in both adrenals and bilateral adrenalectomy was subsequently performed. Histological examination of the resected specimens revealed an adrenocortical carcinoma on the right side and an adenoma on the left side with noticeable cortical atrophy in non-neoplastic adrenals. Immunohistochemical study of steroidogenic enzymes demonstrated that all the steroidogenic enzymes involved in cortisol biosynthesis were expressed in both right and left adrenal tumours. Enzymatic activities of 21, 17alpha, 18, 11beta-hydroxylases were detected in both right and left adrenals except for the absence of 11beta-hydroxylase activity in the left adrenal adenoma. Results of in vitro tissue steroidogenesis examined in short-term tissue culture of the specimens revealed no significant differences between carcinoma and adenoma in cortisol production, but the production of adrenal androgens in carcinoma was significantly higher than that in adenoma, which may indicate the importance of evaluating adrenal androgen levels in patients with adrenocortical neoplasms. (+info)
Steroid hormones modulate H19 gene expression in both mammary gland and uterus.
(21/1561)
H19 is an imprinted and developmentally regulated gene whose product remains apparently untranslated. In a previous study on breast adenocarcinomas, we reported that overexpression of the H19 gene was significantly correlated with the presence of steroid receptors, suggesting the putative role of hormones in H19 transcription. To determine the mode of steroid action, we have detected levels of H19 RNA synthesis during mammary gland development by in situ hybridization (ISH): two peaks of H19 transcription occur during puberty and pregnancy. Furthermore, we demonstrated by ISH that in the uterus H19 RNA synthesis is high during estrus and metestrus phases. To test steroid control of H19 transcription, ovariectomized and adrenalectomized mice were supplemented, 1 week after surgery, with 17-beta-estradiol (E2, 20 microg/kg/day), progesterone (P, 1 mg/kg/day) or corticosterone (B, 0.3 mg/ kg/day) for 2 weeks. According to ISH data, E2 and to a lesser extent B stimulated H19 transcription in the uterus, whereas P inhibited it. To confirm the in vivo results, in vitro experiments were performed using cultures of MCF-7 cells (a hormone-sensitive mammary cell line). E2 stimulated the endogenous H19 gene of this cell line and tamoxifen inhibited this effect. Furthermore, we performed transient cotransfections in MCF-7, in HBL-100 (another hormone-sensitive mammary cell line) and in BT-20 (a hormone-insensitive mammary cell line) with various constructs of ERalpha (WT or mutated) and PR-A, in presence or absence of steroid hormones. We demonstrated that ERalpha up-regulated the H19 promoter in MCF-7 and in HBL-100, whereas PR-A did not have any effect per se. Moreover, in MCF-7, PR-A antagonized clearly the ERalpha-mediated promoter enhancement, but in HBL-100 this counteracting effect on the ERalpha up-regulation was not found. Interestingly, the same experiments performed in BT-20 cell line provided very similar results as those obtained in MCF-7 cells, with a clear down-regulation mediated by PR-A on the H19 promoter. All these in vitro data are in agreement with in vivo results. In addition, data obtained with ERalpha mutants indicate that H19 promoter activation is both ligand-dependent and ligand-independent. We have thus demonstrated that H19 gene expression is controlled by steroid hormones; furthermore, this gene is highly expressed in hormone-sensitive organs when the hormonal stimulation is accompanied with a morphological repair. (+info)
Modulation of triglyceride metabolism by glucocorticoids in diet-induced obesity.
(22/1561)
The involvement of glucocorticoids (GC) in the development of diet-induced obesity and in the concomitant adaptations of triglyceride (TG)-rich lipoprotein metabolism were examined. Rats were fed either rodent chow, which maintains a low lipid flux, or a diet high in sucrose and fat (HSF) that increases lipid flux, leading to metabolic perturbations similar to those that define the plurimetabolic syndrome in humans. The GC status was manipulated through adrenalectomy (ADX) and corticosterone (Cort) replacement. Compared with chow, the HSF diet increased energy intake (17%) and whole body (8%) and adipose tissue (80%) weights. The HSF diet also increased the acute postprandial rise in plasma insulin (4-fold) and TG (3-fold), fasting liver TG content (3-fold), triglyceridemia (54%), and adipose tissue lipoprotein lipase (LPL) activity (2-fold). ADX decreased energy intake and whole body and adipose tissue weights in both dietary cohorts, but more so in HSF-fed than in chow-fed animals. These ADX-induced effects were totally prevented by Cort replacement in rats fed chow, but only partially so in those fed the HSF diet in proportion to the degree of restoration of energy intake. In the chow-fed cohort, the above indexes of TG metabolism remained unaffected by the Cort status, whereas in the HSF-fed cohort, these variables were decreased by ADX to levels of chow-fed animals. Cort replacement in the HSF-fed animals restored indexes of TG metabolism to intact levels and reestablished the diet-related differences observed in intact animals. These findings indicate that GC modulate fasting TG metabolism only minimally when a diet that maintains a low lipid flux is fed. In contrast, their presence is a necessary condition for the development of diet-induced obesity and the concomitant alterations in insulin sensitivity and TG-rich lipoprotein metabolism. (+info)
Adrenalectomy permits a late, local TNF-alpha release in LPS-challenged rat airways.
(23/1561)
The normal rise of circulating endogenous glucocorticosteroids (GCS), in response to immunological stimuli, can be impaired in patients with inflammatory diseases. The aim of this study was to investigate whether abolition of the endogenous GCS response promotes local production of the pro-inflammatory cytokine, tumour necrosis factor (TNF)-alpha, in challenged airways and affects the cellular response in rats. In adrenalectomized or sham operated rats, the trachea and main bronchi were lavaged at various times after intratracheal instillation of low dose lipopolysaccharide (LPS). TNF-alpha in lavage fluid and plasma corticosterone were measured, and cells were differentiated. In adrenalectomized rats, LPS-induced in the airways a biphasic TNF-alpha release peaking at 2 and 6 h, whereas in sham operated rats the second peak was absent; probably inhibited by the strong rise of plasma corticosterone. The second peak was abolished in adrenalectomized rats by pretreatment with exogenous GCS. The LPS-induced neutrophil influx and a decrease in mononuclear cells were prolonged in adrenalectomized rats. In conclusion, abolition of the endogenous glucocorticosteroid response promotes the late release of tumour necrosis factor-alpha in the airways and prolongs the cellular response. This suggests that a normal rise of endogenous glucocorticosteroid after an immunological trigger contributes to a dampening of the late inflammatory activity. (+info)
Glucocorticoids induce glutamine synthetase in folliculostellate cells of rat pituitary glands in vivo and in vitro.
(24/1561)
Glutamine synthetase (GS) is a glucocorticoid-inducible enzyme that has a key role for glutamate metabolism in the central and peripheral nervous system. In this study GS activity was measured and the amount of immunoreactive GS (ir-GS) cells in the rat anterior pituitary gland was quantified as a function of age. In addition, the effects of GS inhibitors, glucocorticoid administration, and adrenalectomy on GS activity were examined. Some of the ir-GS cells were also immunoreactive for S100 protein (ir-S100) which is a known marker for folliculostellate cells (FS) in the anterior pituitary. FS cells expressing GS were first detected in 3-d-old rats, and this cell population, expressed as the immunostained cell area divided by a standard unit area, increased as a function of age. The percentages of FS cells also expressing GS were 0.2, 6.4, 25 and 74% at 3 d, 30 d, 60 d and 2 y of age, respectively. GS enzyme activity also increased in parallel with the increase of ir-GS cell population maturation. The subcutaneous injection of methionine sulphoximine, a GS and gamma-glutamylcysteine synthetase inhibitor, reduced pituitary GS activity by 83%, but increased the population of ir-GS cells 3.5-fold in 30-d-old rats. Buthionine sulphoximine, a specific inhibitor of y-glutamylcysteine synthetase, had little effect on GS activity or the ir-GS cell population. Neither methionine sulphoximine nor buthionine sulphoximine changed the population of ir-S100 protein cells (FS cells). Dexamethasone and hydrocortisone increased the population of ir-GS cells by 3.1 and 4.2-fold, respectively, within 12 h after administration. A significant increase of GS activity due to the injection of glucocorticoids was observed in the anterior pituitary, but not in the brain, retina or liver of immature rats. Adrenalectomy did not cause decrease of pituitary GS activity, and dexamethasone administration increased GS activity in both adrenalectomised and intact rats. In the monolayer culture of anterior pituitary cells, glucocorticoids increased GS activity by x 1.5, and methionine sulphoximine reduced the activity by over 94%. These results demonstrate that GS in folliculostellate cells is a glucocorticoid-inducible enzyme in vivo and in vitro, and that the age-dependent increase of GS activity is independent of endogenous adrenal glucocorticoids. (+info)