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Human Reproduction, Vol. 10, No. 2, pp. 262-267, 1995
© 1995 European Society of Human Reproduction and Embryology

research-article

Physiology: Effects of the pure anti-oestrogen ICI 182780 on oestrogen receptors, progesterone receptors and Ki67 antigen in human endometrium in vivo

M. Dowsett1,4, R. Howell2, J. Salter1, N.M. Thomas3 and E.J. Thomas3

1Academic Department of Biochemistry, Royal Marsden Hospital Fulham Road, London SW3 6JJ 2Queen Charlottes & Chelsea Maternity Hospital Goldhawk Road, London W12 OXG 3Department of Obstetrics & Gynaecology, University of Southampton, Princess Anne Hospital Coxford Road, Southampton S09 4HA, UK

Correspondence: 4To whom correspondence should be addressed

The new steroidal pure anti-oestrogen ICI 182780 was studied for the first time in pre-menopausal women. A total of 30 patients requiring hysterectomy for benign gynaecological disease were randomized to ICI 182780, 12 mg/day i.m. (n = 19) or no treatment (n = 11) for 7 days prior to surgery. Immunohistochemical measurements were made in the snap-frozen, resected endometrium for oestrogen receptors (ER), progesterone receptors (PgR) and Ki67, a nuclear antigen whose expression is closely related to proliferation. Five control patients ovulated prior to surgery and, as expected, the secretory endometria had lower Ki67 antigen concentrations than endometria from the proliferative phase. The endometria from patients treated with ICI 182780 had reduced Ki67 compared with controls. This demonstration of reduced proliferative activity indicates that the pharmacological effectiveness of the treatment was maintained despite increased plasma oestradiol concentrations. In contrast to results from rodents, ICI 182780 did not markedly reduce ER expression, although there was significantly lower ER in the myometrial cells of the treated group. The lack of effect on PgR shows a dissociation between the drug's effect on this oestrogendependent protein and its effects on proliferation.

Key words: anti-oestrogen/endometrium/ICI 182780/Ki67 antigen/steroid receptors


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