The binding of steroids to myometrium and leiomyomata (fibroids) in women treated with the gonadotrophin-releasing hormone agonist Zoladex (ICI 118630).
Since uterine leiomyomata (fibroids) are not found in conditions where oestradiol is either absent or present only in low concentrations, oestradiol is considered to be an important factor in the control of fibroid growth. To investigate whether this is due to a direct effect on the tissue, oestradiol and progestogen receptors were measured in tissue removed at hysterectomy from 12 normally cycling women and 13 women who had received the gonadotrophin-releasing hormone (GnRH) agonist Zoladex (ICI 118630) as a subcutaneous depot given at monthly intervals for 3 months preoperatively and a third group of three women who had received the antioestrogen tamoxifen (20 mg daily) for 3 months before surgery. Both unoccupied oestradiol receptors (measured by separating bound from free hormone with dextran-coated charcoal; DCC) and 'total' receptor populations (as measured by an enzyme immunoassay) were measured in each fibroid and adjoining myometrium. There was significantly more binding of both oestradiol and progestogen to fibroid than to myometrium in both the control (P less than 0.01) and agonist-treated groups (P less than 0.05). Oestradiol binding to fibroids in women treated with Zoladex exceeded that in the normally cycling women (P less than 0.05) which in turn exceeded that in the tamoxifen-treated group (P less than 0.05). However, the binding of progestogen, measured by DCC showed the reverse trend. These results may be explained by the low circulating oestradiol concentration in the GnRH agonist-treated women leading to low receptor occupancy.
Lumsden
M A
MA
Department of Obstetrics and Gynaecology, University of Edinburgh.
West
C P
CP
Hawkins
R A
RA
Bramley
T A
TA
Rumgay
L
L
Baird
D T
DT
D002064:Buserelin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004958:Estradiol / Q000097:blood; D005260:Female; D017273:Goserelin; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy / Q000378:metabolism*; D008597:Menstrual Cycle; D009215:Myometrium / Q000378:metabolism*; D011374:Progesterone / Q000097:blood; D011959:Receptors, Estradiol / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism
D011959:Receptors, Estradiol; D011980:Receptors, Progesterone; D017273:Goserelin; D011374:Progesterone; D004958:Estradiol; D002064:Buserelin