Kinetics of
estradiol dehydrogenase (E2DH) activity and the in vitro effects of
progesterone (P) and synthetic
steroids on E2DH activity were investigated in human normal endometrium and
endometrial carcinoma. In proliferative and secretory endometrium and
endometrial carcinoma, E2DH activities were 1.5 +/- 0.2, 10.1 +/- 1.1 and 1.2 +/- 0.1 nmol/mg
protein/h (mean +/- SEM), Km was 2.3 microM, and Vmax were 0.20, 1.7 and 0.14 nmol/mg
protein/10 min, respectively. Culturing proliferative endometria with
progestogens resulted in a time- and dose-dependent stimulation of E2DH activity up to 72 h and 10(-6) M, respectively.
Medroxyprogesterone acetate had the highest effect to stimulate E2DH activity among the
steroids investigated.
Chlormadinone acetate,
norethindrone, P and
R2323 were also effective. However,
danazol,
lynestrenol and E2 had negligible effect. Histological examination showed that
progestogens caused early secretory change in the proliferative endometrium. These results indicate that the progestational activity is responsible for the elevation of E2DH activity in proliferative endometrium and that the extent to which each
steroid increases E2DH activity may correlate with its local progestational activity. In the
endometrial carcinoma,
progestogens also stimulated E2DH activity in seven cases out of nine during culture for 48 h, but the elevation was lower than that in the proliferative endometrium.