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

PIP: The plasma levels of estradiol-17beta, progesterone, and luteinizing hormone (LH) and pituitary levels of LH were studied in normal rats during the first 6 days of pregnancy, and in rats receiving 2 postcoital doses of Tamoxifen (trans-1-(rho-beta dimethylamino-ethoxyphenyl)-1-2 diphenylbut-1-ene) on Day 2 of pregnancy. Plasma levels of estradiol in untreated animals began to rise on Day 3 of pregnancy and reached a maximum at 20.00 hours on Day 3, before declining early on Day 4. Progesterone levels showed a similar pattern. Although progesterone levels did not vary significantly in treated animals compared to untreated animals, the highest dose of Tamoxifen eliminated the estrogen peak late on Day 3 and levels remained low up to the end of the study period. Lower doses did retard the estrogen peak, but an increase in estrogen was observed on Day 4, which was maintained until Day 6. The high dose of Tamoxifen reduced levels of pituitary LH to extremely low values, while plasma LH concentrations increased 2-3 times the concentrations found in the normal pregnant rat at Day 4. It is suggested that the plasma estradiol peak in early pregnancy is induced by a release of pituitary follicle-stimulating hormone. The antiimplantation effect of Tamoxifen may be due to its ability to inhibit the synthesis of estradiol from progesterone.