Plasma coumestrol levels in sheep following administration of synthetic coumestrol or ingestion of medic hay (Medicago littoralis)

Abstract

Administration of coumestrol to ovariectomized sheep by either intraruminal (i/r) infusion (350 mg/day) or intramuscular (i/m) injection (7.5-–25 mg/day) gave rise to mean plasma levels of 0.6-3.1 µg coumestrol per 100 ml and to near-maximal stimulation of uterine growth. In addition the plasma contained water-soluble conjugates of coumestrol, hydrolysable by molluscan ß-glucuronidase; this fraction was quantitatively more important, relative to 'free' coumestrol, following i/r infusion of coumestrol, but seemed less closely related to oestrogenic action than was "free" plasmacoumestrol.

Feeding on a ration of medic hay (Medicago littoralis), supplying approximately 146 mg coumestrol and 124 mg 4´-methoxycoumestrol per day, gave rise to plasma levels of 0.5–0.7 µg "free" coumestrol and 1.2–4.0 µg conjugated coumestrol per 100 ml, and was associated with oestrogenomimetic changes in the composition of the cervical mucus. 4´-methoxycoumestrol was not detected in the plasma, which suggested that this compound had been converted to coumestrol by O-demethylation in the medic-fed sheep.