The interaction of human endometrial and myometrial steroid receptors with danazol

Abstract

The affinity of danazol for oestrogen, androgen and progesterone receptors in human endometrium and myometrium was determined, to study the mechanism of action of this drug in the treatment of endometriosis. The ability of danazol to combine with each of the three types of receptor was similar in both endometrium and myometrium. The capacity of danazol to compete with oestradiol‐17β for the oestrogen receptor was very low (1·72 ± 0·48 ± 10 cross reaction, mean ± SEM) and danazol, at the maximum concentration used, was unable to saturate the receptor; but danazol's ability to compete with progesterone for its receptor was considerably higher (8·41 ± 1·65% using progesterone, 1·95 ± 0·41% using R5020) and was saturable. Danazol was also able to displace dihydrotestosterone from the cytosol androgen receptor (6·29·1±82% cross reaction). The association constant of oestradiol for the endometrial and myometrial oestrogen receptors was 2·19 ± 10M and 7·45 ± 10M respectively, while that of progesterone and dihydrotestosterone for their receptors was similar in endometrium and myometrium (mean 0·25 ± 0·06 ± 10 M and 3·62·1±67·10 M respectively). Using R5020, the association constant for the myometrial progesterone receptor was 2·50 ± 0·73 ± 10 M. We conclude that, in view of the high circulating levels of danazol present in patients being treated for endometriosis, it is possible that danazol may bind to, and partly saturate, endometrial and myometrial oestrogen, progesterone and androgen receptors during treatment. An explanation may thus be provided for some of the diverse actions of this drug. Copyrigh