Endometrial and Endometriotic Concentrations of Estrone and Estradiol Are Determined by Local Metabolism Rather than Circulating Levels

Kaisa Huhtinen, Reena Desai, Mia Ståhle, Anu Salminen, David J Handelsman, Antti Perheentupa, Matti Poutanen
The Journal of clinical endocrinology and metabolism · 2012 · vol. 97(11) , pp. 4228–4235 · doi:10.1210/jc.2012-1154 · PMID:22969138 · W2065528753
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Endometrial and endometriotic tissue concentrations of estradiol and estrone are regulated by local enzyme activity rather than circulating levels, suggesting localized metabolism drives tissue growth.

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Abstract

CONTEXT: Aberrant estrogen synthesis and metabolism have been suggested to increase local estradiol (E2) concentration in endometriosis and thus to promote the growth of the lesions. However, tissue estrogen concentrations within the endometrium and different types of endometriosis lesions have not been described. OBJECTIVE: The aim of the study was to evaluate local E2 and estrone (E1) concentrations in the endometrium and different types of endometriosis lesions, and to correlate them with the expression of estrogen-metabolizing enzymes. PATIENTS: Patients with endometriosis (n = 60) and healthy controls (n = 16) participated in the study. MAIN OUTCOME MEASURES: We measured serum and tissue concentrations of E2 and E1 as well as mRNA expression of the estrogen-metabolizing enzymes. RESULTS: Endometrial or endometriotic intratissue E2 concentrations did not reflect the corresponding serum levels. In the proliferative phase, endometrial E2 concentration was five to eight times higher than in the serum, whereas in the secretory phase the E2 concentration was about half of that in the serum. Accordingly, a markedly higher E2/E1 ratio was observed in the endometrium at the proliferative phase compared with the secretory phase. In the endometriosis lesions, E2 levels were predominating over those of E1 throughout the menstrual cycle. Among the hydroxysteroid (17β) dehydrogenase (HSD17B) enzymes analyzed, HSD17B2 negatively correlated with the E2 concentration in the endometrium, and HSD17B6 was strongly expressed, especially in the deep lesions. CONCLUSIONS: Endometrial or endometriotic tissue E2 concentrations are actively regulated by local estrogen metabolism in the tissue. Thus, the inhibition of local E2 synthesis is a valid, novel approach to reduce local E2-dependent growth of endometriotic tissue.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Endometrium Estradiol Estrone Ovarian Diseases Peritoneal Diseases Adult Endometriosis Endometriosis Endometrium Estradiol Estradiol Estradiol Estrone Estrone Estrone Female Humans Ovarian Diseases Ovarian Diseases

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