[Effect of gestagen therapy upon estradiol- and progesterone-receptor-level and 17beta-hydroxysteroid dehydrogenase in human endometrial adenocarcinoma (author's transl)]

Abstract

Oestradiol was converted to oestrone about ten time more rapidly by subcellular fractions of normal human endometrium of the secretory phase than by tissue of the proliferative phase. In subcellular fractions of endometrial carcinoma the 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity decreased with decreasing differentiation of the tumour. Most of the 17beta-HSD activity was located in mitochondrial and microsomal fractions of both normal and neoplastic endometrium. After treatment of patients with gestagens only the well differentiated carcinomata significantly increased in 17beta-HSD activity demonstrating that the hormonal stimulus leads to similar effects on the 17beta-HSD activity as in normal endometrium. Furthermore quantitative aspects of the in vitro binding of 3H-oestradiol and 3H-progesterone to receptor components from normal endometrium and endometrial carcinoma cytoplasmic fractions have been studied. In normal tissue the number of cytoplasmic binding sites for both oestradiol and progesterone varied dramatically during the menstrual cycle: number of oestradiol binding sites were highest during the proliferative phase and fell during the secretory phase; for progesterone site the contrary was the case. In all endometrial carcinomata high oestradiol binding activity was observed. In contrast the number of progesterone sites in the tumours was related to the state of differentiation, which paralled the progestional sensitivity of these tumours.

PIP: Endometrium samples were taken from 17 women, aged 43-83, who had endometrial tumors, before and after treatment with gestagen preparations. Samples were also taken from 42 women with normal endometria. The 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity in various fractions of the normal endometria was 10 times higher during the secretory phase than in the proliferation phase. The cytoplasmic estradiol binding receptor molecules (EBRMs) are more prolific at the beginning of the proliferation phase and least frequent in the middle of the secretion phase; the progesterone binding receptor molecule (PBRM) level is inversely proportional to that of the EBRM. In the endometrial tumor tissue, the degree of differentiation of the tumorous tissue determined the 17beta-HSD activity in the various subcellular fractions. Reduction in the differentiation caused reduction in the 17beta-HSD activity. A 3- to 10-fold increase in the 17beta-HSD activity occurred in the well-differentiated tumors after hormonal therapy. High estradiol binding was seen in all of the carcinomata, but the concentration of PBRM increased as differentiation increased or after gestagen treatment was given.