Cholesterol is the starting point of synthesis of steroid hormones and vitamin D. Thus, its uptake, storage, transport, and conversion into respective downstream hormones is of outstanding importance. Cholesterol is taken up into the cell by the cholesterol uptake receptor SR-BI. In adrenal glands, it is stored as cholesterol ester in vesicles that gives the organ its characteristic yellow color. Cholesterol ester is degraded by lipases on demand. Cholesterol ester is transported into mitochondria where it is converted into pregnenolone, the starting point of steroidogenesis. Pregnenolone is converted into a multitude of downstream hormones with the major pathways leading to mineralocorticoids, glucocorticoids, and adrenal androgens. In chronic inflammatory diseases, these pathways are altered so that the major pathway to glucocorticoids is up-regulated at the expense of adrenal androgens. Nevertheless, the amount of secreted glucocorticoids is inadequate in relation to systemic inflammation leading to relative insufficiency. In the animal model of experimental arthritis, we recently demonstrated mitochondrial defects in the chronic phase of the disease which most probably contributes to inadequate low levels of glucocorticoids in relation to inflammation. This presentation highlights defects and alterations in steroidogenesis. These alterations belong to an adaptive program positively selected for short-lived inflammatory episodes but not for chronic life-long inflammation.
Disclosure of Interest None Declared