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Our understanding of the intracrine (or local) regulation of estrogen and other steroid synthesis and degradation expanded in the last decades, also thanks to recent technological advances in chromatography mass-spectrometry. Estrogen responsive tissues and organs are not passive receivers of the pool of steroids present in the blood but they can actively modify the intra-tissue steroid concentrations. This allows fine-tuning the exposure of responsive tissues and organs to estrogens and other steroids in order to best respond to the physiological needs of each specific organ. Deviations in such intracrine control can lead to unbalanced steroid hormone exposure and disturbances. Through a systematic bibliographic search on the expression of the intracrine enzymes in various tissues, this review gives an up-to-date view of the intracrine estrogen metabolisms, and to a lesser extent that of progestogens and androgens, in the lower female genital tract, including the physiological control of endometrial functions, receptivity, menopausal status and related pathological conditions. An overview of the intracrine regulation in extra gynecological tissues such as the lungs, gastrointestinal tract, brain, colon and bone is given. Current therapeutic approaches aimed at interfering with these metabolisms and future perspectives are discussed.

Most endometrial cancers (ECs) are diagnosed at an early stage and have a good prognosis. However, 20-30% develop recurrence and have poor survival. Recurrence-risk prediction at diagnosis is hampered by the scarcity of prognostic markers.Most ECs are estrogen related, and recent studies show that estrogen exposure in EC is controlled intracrinally. We aim at assessing any association between patient prognosis and the pathways controlling the intracrine estrogen generation in EC:(a) the balance between 17 beta-hydroxysteroid-dehydrogenase-type 1 (HSD17B1), that generates active estrogens, and HSD17B2, converting active into poorly active compounds;(b) the balance between steroid sulphatase (STS, that activates estrogens) and estrogen-sulphotransferase (SULTIEI, that deactivates estrogens);(c) the levels of aromatase (ARO), that converts androgen into estrogens.mRNA levels of HSD17B1, HSD17B2, STS, SULTIEI and ARO were determined among 175 ECs using cDNA microarray. Proteins were explored by immunohistochemistry.Patients with high mRNA of HSD17B1 had a poorer prognosis compared with those with low levels. Combining the expression of HSD17B1 and HSD17B2, patients with high tumour expression of HSD17B1 and low levels of HSD17B2 had the poorest prognosis. Contrarily, women that had high tumour levels of HSD17B2 and low of HSD17B1 had the best outcome. No differences were seen between mRNA level of other the genes analysed and prognosis. At the protein level, HSD17B2, STS and SULTIEI were highly expressed, whereas HSD17B1 was low and ARO was almost absent.In conclusion, HSD17B1 is a promising marker to predict EC prognosis. Immunohistochemical detection of this protein in ECs has low sensitivity and should be improved for future clinical applications. (C) 2016 Elsevier Ireland Ltd. All rights reserved.