Dexamethasone suppression test: Corticosteroid receptors regulation in mononuclear leukocytes of young and aged subjects

Zovato, Stefania; Simoncini, Maria Claudia; Gottardo, Christine; Pratesi, C.; Zampollo, V.; Spigariol, A.; Armanini, Decio

doi:10.1007/bf03339594

Cited by 8 publications

(9 citation statements)

References 12 publications

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“…Variation in glucocorticoid sensitivity is due to the presence and concentration of functional receptor [8,10,22], and receptor-modifying factors [3,8,21]. A number of studies indicate that the level of GRs was decreased after treatment with glucocorticoids [2,[12][13][14]. The mRNA levels for GRs also decreased following treatment with exogenous glucocorticoid [2,11,22,23].…”

Section: Discussionmentioning

confidence: 90%

“…Changes in binding characteristics and the level of GR by their cognate ligands are well documented and have been reviewed extensively [11][12][13]. An increase of glucocorticoids reduces the concentration of GRs [14,15].…”

Section: Introductionmentioning

confidence: 99%

“…A number of studies suggest that excess exogenous glucocorticoids induce glucocorticoid resistance [12,20]. Moreover, the unpredictable occurrence of severe side effects during chronic therapy [21], as well as the uncertainty concerning the efficiency of glucocorticoid therapy in chronic immune diseases, have reduced enthusiasm for their use.…”

Section: Introductionmentioning

confidence: 99%

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Glucocorticoid receptors in lymphocytes and stability of kidney graft function

Ribarac-Stepic¹,

Isenović²,

Naumovic³

et al. 2001

Clinical and Experimental Medicine

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The glucocorticoid receptors in lymphocytes of patients treated with glucocorticoids after kidney transplantation have been studied in order to determine whether abnormalities in corticosteroid binding and trans-activation of steroid-receptor complexes, i.e., their translocation into nuclei, may contribute to the resistance of patients to glucocorticoid therapy. The patients were divided into two groups, according to graft stability: patients with stable graft function and those with chronic allograft rejection. The study revealed changes in both level and binding affinity of glucocorticoid receptors in peripheral blood lymphocytes from patients with chronic graft rejection, compared with control level, as well as with values of patients with stable graft function. These data indicate that sensitivity to glucocorticoids depends, at least in part, on the alterations of glucocorticoid receptors. The receptor translocation into nuclei indicates that unknown post-receptor events might also be involved in glucocorticoid resistance that seriously impair successive glucocorticoid therapy after organ transplantation. Further examination of glucocorticoid receptors in cases of organ transplantation seems warranted.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Glucocorticoid receptors in lymphocytes and stability of kidney graft function

Ribarac-Stepic¹,

Isenović²,

Naumovic³

et al. 2001

Clinical and Experimental Medicine

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“…Indeed, there is some evidence in the literature suggesting that changes in GC sensitivity could be the result of chronic GC treatment [54,55] . Reduced intracellular GC receptors may account for the putative underlying mechanisms of age-related GC resistance [15,56,57] , but changes in GR affinity cannot be ruled out. Cellular sensitivity to GCs can also be modulated by changes in peripheral cytokines.…”

Section: Discussionmentioning

confidence: 99%

Healthy Aging Is Associated with Unaltered Production of Immunoreactive Growth Hormone but Impaired Neuroimmunomodulation

Luz

Collaziol

Preissler

et al. 2006

Neuroimmunomodulation

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Background: Both endocrine and immune systems are continuously remodeled during aging. Objective: Here, we investigated to what extent adrenal and somatosenescence are associated reciprocal changes in the immune system during strictly healthy aging. Methods: Forty-six elderly subjects and 33 young adults were recruited according to the health criteria of the SENIEUR protocol. Peripheral blood mononuclear cells were isolated and stimulated in vitro with lipopolysaccharide or phytohemagglutinin to assess the production of immunoreactive growth hormone (GH). Peripheral sensitivity to steroids was assessed in vitroby dexamethasone-, cortisol- or dehydroepiandrosterone (DHEA)-induced inhibition of T-cell proliferation. DHEA and GH levels were measured by radioimmunoassays. Results: Healthy elderly had lower salivary DHEA and serum GH levels (somatosenescence). They presented reduced T-cell sensitivity to dexamethasone but similar cellular sensitivities to cortisol and DHEA. Their cells produced similar levels of immunoreactive GH compared to the cells of young adults. Conclusions: These data indicate that healthy aging is associated with adrenal and somatosenescence as well as impaired neuroendocrine immunoregulation at the level of the lymphocyte. In addition, somatosenescence may not be associated with a reciprocal decline in immunoreactive GH.

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“…3 summarizes putative molecular mechanisms that may account for age-related changes in GC sensitivity. There is some evidence that aging is associated with reduced numbers of intracellular GRs (Grasso et al 1997 ;Zovato et al 1996 ) but changes in GR affinity cannot be ruled out. In addition, altered translocation of GC/GR complex to nucleus and altered acti vity of transcription factors may also explain acquired GC resistance.…”

Section: Potential Mechanisms Of Impaired Gc Signalingmentioning

confidence: 93%