Evaluation of Glucocorticoid Sensitivity and Its Potential Clinical Applicability

Abstract

Glucocorticoids (GC) play an important role in physiologic and pathophysiologic adaptive responses to stress. The majority of these effects are mediated by the GC receptors (GR). GC sensitivity largely depends of the amount of available GR, and their ability to bind the GC-responsive element and/or other nuclear transcription factors, leading to modulation of the expression of GC target genes. Clinical conditions of tissue-specific GC resistance or GC hypersensitivity have been described in several diseases, such as chronic inflammatory and autoimmune conditions, and in visceral obesity, such as metabolic syndrome. Several in vivo and in vitro methods have been described, allowing the evaluation and quantitation of GC sensitivity. The recognition of these parameters has improved our comprehension of the mechanisms involved in those diseases, with potential implications for the diagnosis and therapy of such abnormalities.

Tissue-specific adaptive levels of glucocorticoid receptor alpha mRNA and their relationship with insulin resistance

“…After extraction, RNA was eluted in pure DNase-and RNase-free water (Invitrogen, Cat. #10977023 After reverse transcription for cDNA synthesis, the absolute quantitation of GRα mRNA was determined using quantitative real-time polymerase chain reaction (qRT-PCR) as previously described (Melo et al, 2004;Longui and Faria, 2009;Faria et al, 2010). This method uses the breakpoint cluster region gene (BCR) as a normalizing gene and calibration with standard curves constructed with cDNA from synchronized lymphoblastic cells (Jurkat, ATCC Clone E6-1).…”

“…GC sensitivity is influenced by and directly related to the amount of GC receptor (GR) messenger RNA (mRNA) measured using in vitro methods (Melo et al, 2004;Gross et al, 2009;Longui and Faria, 2009;Faria et al, 2010; Sousa e Silva et al, 2010).…”

Determination of steroid response by abdominal ultrasound in cases with autoimmune pancreatitis

“…In the current study, focusing on the steroid response of serum IgG, cases with a high sIgG response during the initial phase of steroid administration showed a higher relapse rate. Steroid sensitivity is known to differ in each individual in a tissue-specific manner [31,32] according to various factors including polymorphism of steroid receptor genes, the number of steroid receptors, physical exercise, etc. Strong effects in response to steroids, in other words, may reflect the high dependency on steroids; hence, these cases may need longer maintenance therapy.…”

Biological analysis of endocrine-disrupting chemicals in animal meats from the Pearl River Delta, China

“…Circulating concentrations of steroid hormones such as estrogen, (E 2 ), progesterone (P) and androgens have been hypothesized to influence cancer risk, including breast, ovarian, testicular and prostate cancers (Lukanova and Kaaks, 2005;Folkerd and Dowsett, 2010). Chronic exposure to the ligand of PPAR induces development of cancers in livers of both rats and mice (Reddy et al, 1980(Reddy et al, , 1976Rao and Reddy 1987;Pyper et al, 2010), whereas elevated concentrations of glucocorticoids in blood might lead to insulin resistance and diabetes (Chrousos and Kino, 2009;Longui and Faria, 2009;Barnes, 2010). EDCs with retinoic acid-like activities can interfere with embryonic development and differentiation of secondary characteristics of males (Bowles et al, 2006;Bowles and Koopman, 2007).…”