Patients With IgA Nephropathy Have Altered Levels of Immunomodulatory C19 Steroids. Glucocorticoid Therapy With Addition of Adrenal Androgens May Be the Choice

Abstract

Glucocorticoid (GC) therapy is one of the methods of choices for treatment of autoimmune diseases (ADs). In addition, adrenal androgens are known as immunoprotective GC-antagonists. Adrenal steroids preferentially influence the Th1-components over the Th2 ones. We investigated steroid metabolome (using gas chromatography-mass spectrometry) in healthy controls (H), GC-untreated patients with ADs different from IgA nephropathy (U), GC-treated patients with ADs different from IgA nephropathy (T) and in patients with IgA nephropathy (IgAN), which were monitored on the beginning (N0), after one week (N1) and after one month (N2) of prednisolone therapy (60 mg of prednisolone/day/m2 of body surface). Between-group differences were assessed by one-way ANOVA, while the changes during the therapy were evaluated by repeated measures ANOVA. The ANOVA testing was followed by Duncan’s multiple comparisons. IgAN patients and patients with other ADs exhibited lack of adrenal androgens due to attenuated activity of adrenal zona reticularis (ZR). Androgen levels including their 7α-, 7β-, and 16α-hydroxy-metabolites were further restrained by GC-therapy. Based on these results and data from the literature, we addressed the question, whether a combination of GCs with Δ5-steroids or their more stable synthetic derivatives may be optimal for the treatment of antibodies-mediated ADs.

Activation of Adrenal Steroidogenesis and an Improvement of Mood Balance in Postmenopausal Females after Spa Treatment Based on Physical Activity

“…In these diseases, the CRH operates on both peripheral and central levels [4,5]. The CRH indirectly operates in an anti-inflammatory fashion via the stimulation of anti-inflammatory cortisol and immunoprotective adrenal androgens [6], while the autocrine/paracrine peripheral effect is the opposite [7].…”

“…The data from the FZ as reported by Siriani et al [13] showed increased mRNA expression of the genes needed for DHEAS production, such as steroidogenic acute regulatory protein, cholesterol desmolase (CYP11A1), steroid C17-hydroxylase-C17,20-lyase (CYP17A1), and type 2A1 steroid sulfotransferase (SULT2A1), as well as the upregulation of type 1 CRH receptors after 24 h treatment of FZ cells with CRH, CRH-related peptide urocortin or ACTH. The various adrenal steroids that have synthesis controlled by CRH and ACTH as well as their metabolites may operate as neuroactive [14], neuroprotective [15] and immunoprotective [6] substances, affecting the somatic, psychosomatic and psychiatric health of patients [16][17][18][19].…”

May Circulating Steroids Reveal a Predisposition to Intrahepatic Cholestasis of Pregnancy in Non-Pregnant Women?

“…The reduced activity of CYP17A1 C17,20-lyase step in ICP patients might also be associated with an impaired expression of CYB5 enzyme (Rege et al 2016) in the maternal zona reticularis. We have also found attenuated activity of the CYP17A1 C17,20 lyase step in further pathologies such as IgA nephropathy (Sterzl et al 2017), mood and anxiety disorders and Alzheimer's disease (Vankova et al 2016). This insufficiency was sometimes accompanied by reduced sulfotransferase activity (Vankova et al 2015).…”

A method for determination of one hundred endogenous steroids in human serum by gas chromatography-tandem mass spectrometry.

“…The present GC-MS/MS method includes a wide range of analytes, which reflect activities of most steroidogenic enzymes. Thus, it could be used for the estimation of changes in steroidogenesis for various physiological and pathophysiological situations and subsequently the data obtained can be utilized for uncovering the mechanisms of some steroidrelated human pathologies (Parizek et al 2016, Sterzl et al 2017.…”

“…Steroid profiling helps various pathologies to be rapidly diagnosed. Moreover, the results from analyses investigating steroidogenic pathways may be used as a tool for uncovering pathology causations and proposals of new therapeutic approaches (Bicikova et al 2013, Hill et al 2010c, Kanceva et al 2015, Parizek et al 2016, Sosvorova et al 2015, Sterzl et al 2017.…”