Several factors which affect the sensitivity of calcitonin bioassay were investigated. As to the assay animals, Sprague-Dawley and Holtzman rats were more sensitive than Wistar rats. In mice, C3H III strain gave better response to calcitonin than CF 1 and ddN strains. In each strain, younger rats were more sensitive than older ones. It was also demonstrated that the longer was the period of low calcium diet, the more remarkable was the response of the Wistar rats to calcitonin. In Wistar rats, phosphate in drinking water improved the sensitivity of the assay and intravenous administration of calcitonin produced steeper dose-response curve than subcutaneous administration.
When 3 to 4-week-old Sprague-Dawley rats were utilized, the hypocalcemic acitivity was detected in 25 to 66 mg of wet weight of human thyroid glands, while 5-week-old Sprague-Dawley rats were not so sensitive as to be able to detect hypocalcemic activity in 100mg of wet weight of human thyroid glands.
Two-week-old Holtzman rats were so sensitive that we detected hypocalcemic activity in 1mg of wet weight of a metastatic lymph node of the medullary thyroid carcinoma.