The hypothalamic-pituitary-adrenal and gonadal axis in rheumatoid arthritis

Journal/Book: Z Rheumatol 1999; 58: 303. 1999;

Abstract: M. Cutolo; Division of Rheumatology Department of Internal Medicine University of Genova The hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis involvement or response to immune activation seems crucial for the control of excessive inflammatory and immune conditions such as autoimmune rheumatic diseases including rheumatoid arthritis (RA). However female patients seem to depend more on the HPA axis whereas male patients seem to depend more on the HPG axis activities. Hypoandrogenism may play a pathogenetic role in male RA patients since adrenal and gonadal androgens both final products of the HPA and HPG axes are considered natural immunosuppressors. A significantly altered steroidogenesis of adrenal androgens (i.e. dehydroepiandrosterone sulfate =DHEAS and DHEA) in non glucocorticoid treated premenopausal RA patients has been described. The observation of reduced DHEA production combined with unexpected normal cortisol levels during oCRH and ACTH testing further support the concept of the presence of an adrenal hypofunction in active RA patients in the setting of a sustained inflammatory process as shown by high IL-6 and IL-12 concentrations. In addition the reduced basal concentration of adrenal androgens in RA might be due both to a decreased pooling and a reduced sensitivity of the adrenal gland to exogenous corticotropin or alternatively to a partial enzymatic defect (i.e. 17 20 hydroxylase). The menopausal peak of RA suggests that estrogens and/or progesterone deficiency also play a role in the disease and many data indicate that estrogens might suppress cellular immunity (Th2-type response) but stimulate humoral immunity (Th1-type response). Murine and human and synovial macrophages exhibit functional cytoplasma and nuclear sex hormone receptors. ... le

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