Intra-tissue steroid profiling indicates differential progesterone and testosterone metabolism in the endometrium and endometriosis lesions

Abstract

Context: Aberrant sex steroid signaling is suggested to promote endometriosis growth by several mechanisms, and the tissue concentrations of sex steroids are key determinants of the hormone action. However, their concentrations are only superficially known in the endometrium and endometriosis lesions. Objective: This study sought to evaluate whether the tissue steroid hormone concentrations in endometriosis differ from the endometrium or serum. Main Outcome Measures: Steroid analysis of serum and tissue specimens of women with endometriosis (n = 60) and healthy controls (n =16) was measured, and supporting data from quantitative RT-PCR for steroidogenic enzymes and explant cultures of a subset of specimens is provided. Results: Endometrial tissue progesterone (P4) concentrations reflected the serum P4 levels during the menstrual cycle, whereas in endometriosis lesions, the cycle-dependent change was missing. Remarkably high tissue T concentrations were measured in endometriosis lesions independent of the cycle phase, being 5-19 times higher than the corresponding serum levels. Tissue/serum ratio of T was further increased in patients with contraceptive medication. The altered tissue steroid concentrations in endometriosis were in line with the expression of various steroidogenic enzymes in the lesions, of which HSD3B2 showed constantly high expression, whereas CYP11A1 expression was low. Furthermore, the high concentration of sex steroids detected in the ovarian lesions involves their production by the lesion and by the adjacent ovarian tissue. Conclusions: Endometriosis lesions present with progestin and androgen metabolism, which are different from that of the endometrium, and the lesions are characterized by high tissue T and a loss of cyclical changes in tissue P4 concentration.