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

组织内类固醇分析表明子宫内膜和子宫内膜异位症病变中的孕酮和睾酮代谢存在差异

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作者:Kaisa Huhtinen, Taija Saloniemi-Heinonen, Pekka Keski-Rahkonen, Reena Desai, Daniel Laajala, Mia Ståhle, Merja R Häkkinen, Michael Awosanya, Pia Suvitie, Harry Kujari, Tero Aittokallio, David J Handelsman, Seppo Auriola, Antti Perheentupa, Matti Poutanen

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.

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.

Trial registration

ClinicalTrials.gov NCT01301885.

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