Prolonged treatment with the synthetic glucocorticoid methylprednisolone affects adrenal steroidogenic function and response to inflammatory stress in the rat.
Abstract
Synthetic glucocorticoids are widely prescribed for the treatment of numerous inflammatory and autoimmune diseases and they can also affect the way the adrenal gland produces endogenous glucocorticoids. Indeed, patients undergoing synthetic glucocorticoid treatment can develop adrenal insufficiency, a condition characterised by reduced responsiveness of the adrenal to ACTH stimulation or stressors (e.g. surgical or inflammatory stress). To better elucidate the long-term effect of synthetic glucocorticoids treatment and withdrawal on adrenal function, we have investigated the long-term effects of prolonged treatment with methylprednisolone on HPA axis dynamics and on the adrenal steroidogenic pathway, both in basal conditions and in response to an inflammatory stress (lipopolysaccharide, LPS). We have found that 5-days treatment with methylprednisolone suppresses basal ACTH and corticosterone secretion, as well as corticosterone secretion in response to a high dose of ACTH, and down-regulates key genes in the adrenal steroidogenic pathway, including StAR, MRAP, CYP11a1 and CYP11b1. These effects were paralleled by changes in the adrenal expression of transcription factors regulating steroidogenic gene expression, as well as chan...Continue Reading
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