In vitro effect of synthetic progestogens on estrone sulfatase activity in human breast carcinoma.
The effect of progesterone and nine synthetic progestogens on the activity rate of microsome estrone sulfatase obtained from human breast carcinoma tissues was studied. The progestogens were classified into three groups: group I with a strict inhibitor effect: demegestone and chlormadinone acetate; group II with a strict activator effect: medroxyprogesterone acetate, quingestanol acetate, lynestrenol and progesterone and group III with a nonsignificant effect: dydrogesterone, promegestone, norgestrel and danazol. Demegestone was the most potent inhibitor and medroxyprogesterone acetate and quingestanol acetate had the highest activator effect. The effect of Triton X-100, a nonionic detergent, was also tested. This detergent consistently increased the microsome estrone sulfatase activity. A comparison was made between the effects of demegestone, medroxyprogesterone acetate and danazol on estrone sulfatase activity measured with or without Triton X-100 in the incubation medium. The presence of the detergent modified the progestogen action. Our results suggest that synthetic progestogens can influence the estrone sulfatase activity measured in human breast carcinoma tissues. However, the effect of progestogens was dependent on experimental conditions. Progestogens such as demegestone and chlormadinone acetate which inhibited estrone sulfatase activity in intact preparations, can reduce the intracellular production of biological active estrogen via the sulfatase pathway.
Prost-Avallet
O
O
Unité de Recherches de Biochimie Hormonale et des Régulations, INSERM U 198, Besançon, France.
Oursin
J
J
Adessi
G L
GL
D001943:Breast Neoplasms / Q000201:enzymology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D017830:Octoxynol; D011092:Polyethylene Glycols / Q000494:pharmacology; D045167:Progesterone Congeners / Q000494:pharmacology*; D013429:Sulfatases / Q000037:antagonists & inhibitors / Q000187:drug effects*
D045167:Progesterone Congeners; D011092:Polyethylene Glycols; D017830:Octoxynol; D013429:Sulfatases; C020121:estrone sulfatase