THE INTERACTION OF HUMAN ENDOMETRIAL AND MYOMETRIAL STEROID RECEPTORS WITH DANAZOL

Clinical Endocrinology - Tập 19 Số 3 - Trang 377-388 - 1983
Graham Jenkin1, C. I. Cookson1, G. D. Thorburn1
1Department of Physiology and Pharmacology, University of Queensland, St. Lucia, Qld. 4067, Australia, and Department of Physiology, Monash University, Clayton, Vic. 3168, Australia

Tóm tắt

SUMMARYThe 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 ± 10−3% 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 ± 109M‐1 and 7·45 ± 109M‐1 respectively, while that of progesterone and dihydrotestosterone for their receptors was similar in endometrium and myometrium (mean 0·25 ± 0·06 ± 109 M‐1 and 3·62·1±67·109 M‐1 respectively). Using R5020, the association constant for the myometrial progesterone receptor was 2·50 ± 0·73 ± 109 M−1. 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.

Từ khóa


Tài liệu tham khảo

10.1016/S0002-9378(16)33237-9

10.1016/S0015-0282(16)42732-9

BARBIERI R. L., 1980, Danazol binding to rat androgen, glucocorticoid, progesterone, and oestrogen receptors: correlation with biological activity, Fertility and Sterility, 31, 426

BLACKMORE W. P., 1977, Danazol in the management of benign breast disease, Journal of International Medical Research, 5, 101

CHARD T., 1978, Laboratory Techniques in Biochemistry and Molecular Biology, 293

CHIMBIRA T. H., 1977, Preliminary results in treatment of menorrhagia with danazol, Journal of International Medical Research, 5, 98

10.1111/j.1471-0528.1979.tb10683.x

COOKSON C. I., 1982, Interaction of danazol with human steroid binding proteins, Proceedings of the Endocrine Society of Australia, 25, 81

DMOWSKI W. P., 1975, Treatment of endometriosis with an antigonadotrophin, danazol, Obstetrics and Gynaecology, 46, 147

DMOWSKI W. P., 1978, Danazol:—a synthetic steroid derivative with interesting physiological properties, Fertility and Sterility, 22, 9, 10.1016/S0015-0282(16)37981-X

10.1095/biolreprod10.4.438

10.1016/S0015-0282(16)42733-0

10.1111/j.1479-828X.1978.tb00063.x

10.2165/00003495-198019050-00004

10.1016/S0015-0282(16)38045-1

GREENBLATT R. B.&GUITIERREZ M.(1976)Summation of the role of danazol in therapy of endometriosis.Int. Cong. Ser. No. 368 Recent Advances in Endometriosis Excerpta Medica 116–128.

GUILLEBAUD J., 1977, Endocrine effects of danazol in menstruating women, Journal of International Medical Research, 5, 57

10.1210/jcem-40-6-1001

10.1210/jcem-31-4-362

10.1111/j.1479-828X.1980.tb00107.x

10.1210/endo-101-3-920

10.1016/0005-2795(73)90340-1

LAUERSEN N. H., 1976, The effect of danazol in the treatment of chronic cystic mastitis, Obstetrics and Gynecology, 48, 93

LAUERSEN N. H., 1975, Danazol: an antigonadotropic agent in the treatment of pelvic endometriosis, American Journal of Obstetrics and Gynecology, 123, 742, 10.1016/0002-9378(75)90499-8

10.1210/endo-104-3-791

LOHIYA N. K., 1977, The oestrogenic activity of danazol in the female gerbil (Meriones hurrianae Jerdon, Ind-Endokrinologie, 69, 169

10.1038/274276a0

MURPHY L. C., 1979, Binding of antioestrogens to human mammary tumor cytosols, Proceedings of the Endocrine Society of Australia, 22, 67

10.1016/0010-7824(78)90061-6

10.1016/0010-7824(74)90112-7

POTTS G. O., 1977, Pharmacology of danazol, Journal of International Medicine Research, 5, 1

RODBARD D., 1973, Advances in Experimental Medicine and Biology, 289

10.1172/JCI106917

10.1111/j.1365-2265.1981.tb02966.x

TAMAYA T., 1978, Mechanism of antiprogestational action of synthetic steroids, Acta endocrinologica (Copenh), 88, 190

10.1016/0022-4731(79)90513-2

10.1016/S0039-128X(70)80093-9

TRIBRIS J. C. M., 1978, Distribution of cytoplasmic estrogen and progesterone receptors in human endometrium, American Journal of Obstetrics and Gynecology, 132, 449, 10.1016/0002-9378(78)90783-4

10.1016/0005-2795(73)90234-1

10.1016/0002-9378(76)90554-8

WOOD G. P., 1975, Hormonal changes associated with danazol therapy, Obstetrics and Gynecology, 45, 302

Thông tin
Thông tin xuất bản

Clinical Endocrinology

Tập 19 Số 3

377-388

Thông tin tác giả