Reduction of plasma prolactin by acute administration of CB-154 in ovariectomized F344 and Holtzman rats treated with diethylstilbestrol: A comparison of RIA and Nb 2 lymphoma bioassay

Abstract

Fischer 344 (F344) and Holtzman Sprague-Dawley female rats were ovariectomized and implanted with a s.c. Silastic capsule of diethylstilbestrol (DES). At 1,4 and 8 weeks of DES exposure, blood samples were obtained by infraorbital sinus puncture under light ether anesthesia before and 2 hours after s.c. administration of CB-154 (2.5 mg/rat). The plasma obtained was assayed for prolactin by radioimmunoassay (RIA) and Nb 2 lymphoma cell bioassay (BA). At 1 week of DES treatment plasma prolactin in F344 rats measured by RIA was decreased by CB-154 (≈ 60%) whereas the level measured by BA was not changed and the BA:RIA ratio was increased from 2.4 +/− 0.2 to 4.8 +/− 0.9. CB-154 decreased plasma prolactin levels at 4 weeks but the effect seen by RIA (∼80%) was greater than that seen by BA (∼60%) and the BA:RIA ratio was increased (2.2 +/− 0.2 vs 3.4 +/− 0.5). By 8 weeks of DES exposure, CB-154 was as effective in reducing the levels measured by BA (∼89%) as those measured by RIA (∼85%) and the BA:RRIA was not affected by the dopamine agonist. In Holtzman rats CB-154 decreased prolactin levels measured by RIA and BA to the same extent at both 1 and 4 weeks resulting in no change in the BA:RIA ratio, but at 8 weeks the BA:RIA was decreased by CB-154 (2.1 +/− 0.1 to 1.7 +/−0.1). As was observed in F344 rats, the reduction in plasma prolactin induced by CB-154 increased as the duration of DES treatment increased (1 week ∼45%; 4 weeks ∼55–60%; 8 weeks ∼80–85% inhibition) regardless of assay method. It is concluded that DES increases the BA:RIA ratio of plasma prolactin and that acute CB-154 treatment increases, decreases or does not change the BA:RIA ratio depending on the strain of rat used and the duration of DES treatment.