The relationship between oestradiol metabolism and adrenal steroids in the endometrium of postmenopausal women with and without endometrial cancer.
The aim of the present study was to investigate the hypothesis that adrenal androgens are contributory to the development of endometrial cancer either by the oestrogenic action of 5-androstene-3 beta, 17 beta-diol (androstenediol) or through the inhibition of oestradiol metabolism. Concentrations of androstenediol, dehydroepiandrosterone (DHA), DHA sulphate (DHAS), oestrone and oestradiol were measured in plasma and endometrium from postmenopausal women with and without endometrial cancer. There was no difference between normal postmenopausal women and endometrial cancer patients with respect to either tissue or plasma adrenal androgens although there was a tendency for plasma DHAS levels to be increased in cancer patients (normal women: 640 +/- 156 ng/ml; cancer patients: 808 +/- 159 ng/ml). There was a positive correlation between endometrial tissue concentrations of androstenediol and DHA in both normal women (P less than 0.05) and cancer patients (P less than 0.01) but for DHAS the relationship was only significant for non-malignant tissue (androstenediol: DHAS, P less than 0.05; DHA: DHAS, P less than 0.02). A significant positive correlation was found between all three plasma adrenal androgens for both groups. In cancer patients there was a trend towards an inverse correlation between endometrial tissue concentrations of DHAS and the enzyme 17 beta-hydroxysteroid dehydrogenase (17OHSD) although the relationship was not significant (r = 0.49). In endometrium, oestradiol was present in significantly higher concentrations than oestrone whereas in plasma the reverse was the case. There was also a tendency for plasma oestradiol levels to be elevated in the cancer subjects. These data do not support a substantial role for adrenal androgens in endometrial cancer but suggest that a relationship may exist between DHAS and 17OHSD and that an imbalance between sulphatase and sulphotransferase activities may be involved.
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000302:Adrenal Cortex / Q000503:physiopathology; D015114:Androstenediol / Q000097:blood; D003687:Dehydroepiandrosterone / Q000097:blood; D004717:Endometrium / Q000378:metabolism / Q000503:physiopathology*; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D014594:Uterine Neoplasms / Q000097:blood / Q000209:etiology* / Q000503:physiopathology
D003687:Dehydroepiandrosterone; D004958:Estradiol; D015114:Androstenediol; D015067:17-Hydroxysteroid Dehydrogenases; C032690:3-alpha-(17-beta)-hydroxysteroid dehydrogenase (NAD(+))