Pituitary Nuclear Retention of Dexamethasone and ACTH Biosynthesis

Koch, Bernard; Bucher, Bernard; Mialhe, C

doi:10.1159/000122327

Cited by 27 publications

(12 citation statements)

References 10 publications

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“…In addition, it has been shown that dexamethasone's blockade of ACTH release might involve a DNA-dependent RNA synthesis, thus suggesting a genomic level of action of the steroid. This idea is further supported by our previous report indicating the presence of receptors for dexamethasone (Dx) within the nuclear fraction of the pituitary [Koch et al, 1974],…”

supporting

confidence: 75%

“…After completion of incubation the glands were washed in ice-cold saline, and processed as previously described [Koch et al, 1974] in order to isolate the purified nuclear fraction and the 105,000 x g supernatant. The separation of bound and unbound steroid was per formed by passing cytosol through a column (13 x 0.6 cm) of Sephadex G-25 at 4°C.…”

Section: Methodsmentioning

confidence: 99%

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Glucocorticoid Binding to Adenohypophysis Receptors and its Physiological Role

et al. 1975

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The binding characteristics of glucocorticoids to cytoplasmic and nuclear fractions of the adenohypophysis were determined and an attempt was made to correlate steroid uptake with physiological action. Binding was of high affinity and exhibited a limited number of acceptor sites for dexamethasone (Dx). It was shown that the steroid-receptor complex dissociated rapidly at 37 °C, but was stable at low temperatures. An inverse relationship was detected between the plasma corticosterone (B) titer and the capacity of receptors to combine ³H-Dx. Shortly after stress or injection of physiological doses of B, 50 to 70% of the acceptor sites were saturated. Progressive desaturation of the occupied receptors appeared to depend upon time and the plasma B concentration. Some evidence was also provided supporting a possible correlation between the extent of Dx inhibition of in vitro ACTH secretion and the degree of binding sites’ occupancy. These results suggest that glucocorticoid binding to pituitary receptors may be correlated with the physiological action of the steroids on ACTH release.

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supporting

confidence: 75%

Section: Methodsmentioning

confidence: 99%

Glucocorticoid Binding to Adenohypophysis Receptors and its Physiological Role

et al. 1975

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“…We have shown here that VIP concentrations in discrete brain re gions and in the adenohypophysis are directly related to plasma corticosteroids levels. Adrenalectomy modifies VIP concentrations in the hippocampus and in the adenohypo physis, two structures known to contain relatively large amounts of specific corticosteroid receptors [9,19,24,29,36,37], This effect seems to be due to corticosteroids since the ablation of the adrenal medulla has no effect on VIP content of these structures and that restoration of changes in VIP concentrations following adrenalectomy is obtained by corticosteroid administration.…”

Section: Discussionmentioning

confidence: 99%

Effect of Steroids on Vasoactive Intestinal Peptide in Discrete Brain Regions and Peripheral Tissues

et al. 1980

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The effect of castration and adrenalectomy was studied on vasoactive intestinal peptide (VIP) concentrations in various brain and peripheral structures of male rats. Castration has no effect on any of the structures studied, whereas 4 weeks adrenalectomy (ADX) decreases VIP concentrations in the hippocampus and increases them in the adenohypophysis, two structures known to contain large amounts of glucocorticoid receptors. Corticosterone administration restores VIP levels to control values only in the dorsal hippocampus. In contrast, dexamethasone counteracts both the decrease and the increase of VIP concentrations obtained after ADX in the hippocampus and in the adenohypophysis respectively. The present results suggest that corticosteroids can be involved in the regulation of VIP actions both in the brain and in the adenohypophysis.

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“…As previously described (Koch et al 1974), anterior pituitaries were homogenized in buffer containing 0·01 M MgCl 2 , 0·025 M KCl and 0·002 M dithiothreitol (pH 7·4). Protein concentrations of the homogenates were determined using the method of Bradford (1976).…”

Section: Anterior Pituitary [ 3 H]corticosterone Nuclear Uptakementioning

confidence: 99%

Testosterone-dependent variations in plasma and intrapituitary corticosteroid binding globulin and stress hypothalamic-pituitary-adrenal activity in the male rat

Viau

Meaney²

2004

Journal of Endocrinology

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Hypothalamic-pituitary-adrenal (HPA) activity is governed by glucocorticoid negative feedback and the magnitude of this signal is determined, in part, by variations in plasma corticosteroid-binding globulin (CBG) capacity. Here, in gonadectomized male rats we examine the extent to which different testosterone replacement levels impact on CBG and HPA function. Compared with gonadectomized rats with low testosterone replacement ( 2 ng/ ml), plasma adrenocorticotropin and -endorphin/ -lipotropin responses to restraint stress were reduced in gonadectomized rats with high testosterone replacement ( 5 ng/ml). Plasma CBG levels also varied negatively as a function of testosterone concentration. Moreover, glucocorticoid receptor binding in the liver was elevated by higher testosterone replacement, suggesting that testosterone acts to enhance glucocorticoid suppression of CBG synthesis. Since pituitary intracellular CBG (or transcortin) is derived from plasma, this prompted us to examine whether transcortin binding was similarly responsive to different testosterone replacement levels. Transcortin binding was lower in gonadectomized rats with high plasma testosterone replacement ( 7 ng/ml) than in gonadectomized rats with low testosterone replacement ( 2 ng/ml). This testosterone-dependent decrease in pituitary transcortin was associated, in vitro, with an enhanced nuclear uptake of corticosterone. These findings indicate that the inhibitory effects of testosterone on corticotrope responses to stress may be linked to decrements in plasma and intrapituitary CBG. This could permit greater access of corticosterone to its receptors and enhance glucocorticoid feedback regulation of ACTH release and/or proopiomelanocortin processing.

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Pituitary Nuclear Retention of Dexamethasone and ACTH Biosynthesis

Cited by 27 publications

References 10 publications

Glucocorticoid Binding to Adenohypophysis Receptors and its Physiological Role

Glucocorticoid Binding to Adenohypophysis Receptors and its Physiological Role

Effect of Steroids on Vasoactive Intestinal Peptide in Discrete Brain Regions and Peripheral Tissues

Testosterone-dependent variations in plasma and intrapituitary corticosteroid binding globulin and stress hypothalamic-pituitary-adrenal activity in the male rat

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