The antiestrogen LY117018 blocks effects of estradiol on pituitary glucose-6-phosphate dehydrogenase specific activity and on serum LH.

Neuroendocrine effects of the antiestrogen LY117018 were investigated in C57BL/6J mice. A series of subcutaneous injections of 17 beta-estradiol (E2) into ovariectomized mice increased pituitary glucose-6-phosphate dehydrogenase (G6PDH) specific activity, increased uterine wet weight, and suppressed the postovariectomy rise in serum LH. Simultaneous administration of LY117018 completely reversed the effects of E2 on G6PDH activity and uterine weight, and partially reversed the negative feedback of E2 on luteinizing hormone (LH). When administered in the absence of E2, LY117018 had no effect on G6PDH activity or serum LH, but increased uterine weight by 70%. Thus, LY117018 effectively antagonizes the effects of E2 at both uterine and pituitary levels, but acts as a partial agonist only in the uterus.