Effects of tamoxifen on concentrations of luteinizing hormone and follicle-stimulating hormone in the plasma of ovariectomized ewes.

Abstract

The effects of tamoxifen on peripheral plasma concentrations of gonadotrophins were studied in ovariectomized ewes. First, ovariectomized ewes were injected (i.m.) with 10 mg tamoxifen citrate/day for 4 days which caused a significant reduction in plasma LH concentrations within 4 days and plasma FSH concentrations within 1 day of the commencement of treatment. Further groups of ovariectomized ewes were then injected (i.m.) with two injections of 10 mg tamoxifen citrate 6 h apart or 20 micrograms oestradiol benzoate (OB) or tamoxifen citrate plus OB or oil. Tamoxifen treatment caused a reduction in plasma LH and FSH concentrations within 6 h. In four of our ewes receiving OB, a surge in LH secretion was observed; a similar response was observed in two out of four ewes given the combination of tamoxifen citrate and OB. No LH surge was seen in ovariectomized ewes given tamoxifen alone. These results show that tamoxifen reduces plasma gonadotrophin levels in ovariectomized ewes suggesting it is an oestrogen agonist in the sheep pituitary gland. A partial oestrogen antagonist action of tamoxifen is similarly suggested by its ability to block the oestrogen-induced LH surge in some ovariectomized ewes. Since tamoxifen consistently lowers plasma gonadotrophin levels in ovariectomized ewes this could result from action via oestrogen receptors or by central nervous system, non-oestrogen receptor-mediated effects.