PLASMA HORMONES AND PITUITARY LUTEINIZING HORMONE IN THE RAT DURING THE EARLY STAGES OF PREGNANCY AND AFTER POST-COITAL TREATMENT WITH TAMOXIFEN (ICI 46,474)

Abstract

SUMMARY Plasma levels of oestradiol-17β, progesterone and luteinizing hormone (LH) and pituitary levels of LH have been measured during the first 6 days of pregnancy, in normal rats and in rats receiving two doses of Tamoxifen (trans-1-(p-β dimethylamino-ethoxyphenyl)-1-2 diphenylbut-1-ene) on day 2 of pregnancy. In normal rats oestradiol rose strongly from early on day 3 to reach a peak concentration between 22.00 h on day 3 and 08.00 h on day 4. Progesterone concentrations rose from day 2 to reach peak values on day 3–4. In animals in which implantation was delayed 20–24 h by administration of Tamoxifen (0·1 mg/kg) orally on day 2 the increased level of plasma oestrogen was also delayed by 20 h. A higher dose of Tamoxifen (0·2 mg/kg) on day 2, which prevented implantation, completely eliminated the increase in plasma oestradiol. Neither dose of Tamoxifen affected the levels of progesterone. In both normal rats and rats treated with 0·1 mg Tamoxifen/kg, plasma LH levels declined by day 3 while pituitary levels rose steadily. There was no detectable change in either plasma or pituitary LH levels, accompanying the increase in plasma oestradiol in the normal rats. In animals receiving Tamoxifen (0·2 mg/kg), plasma LH increased to a maximum by day 4 while levels of pituitary LH decreased. The results show that the oestrogen ' surge' of early pregnancy, occurs normally about midnight on day 3 and not late on day 4 as previously thought. It is considered that the plasma oestradiol peak in early pregnancy results from an increased release of FSH rather than an increased release of LH. Tamoxifen may owe part of its antifertility action to a capacity to inhibit the synthesis of oestradiol from progesterone.