Effects of testosterone on skeletal growth in lambs as assessed by labeling index of chondrocytes in the metacarpal bone growth plate.

Abstract

The effects of testosterone on the epiphyseal growth plate of metacarpal bones of growing sheep were evaluated in 20 rams, 20 wethers, and 20 wethers receiving subcutaneous testosterone replacement therapy. Two animals from each testosterone treatment group were slaughtered at 14-d intervals from 49 to 133 d, and then at 28-d intervals until 217 d, for a total of 10 slaughter ages. Immediately after slaughter, the cannon bones were dissected of extraneous tissue, weighed, and their lengths measured. Growth plates from the metacarpal bones were isolated and explants were cultured for 24 h in medium containing [3H]thymidine. After autoradiography, labeling index was calculated as the ratio of labeled to total nuclei in the resting and proliferative zones of the growth plate. Testosterone increased (P < .03) weight and length of the metacarpal bone. Increased bone length due to testosterone was associated, in part, with a higher (P < .05) labeling index in chondrocytes of the proliferative zone of the growth plate. Labeling indices in the resting zone chondrocytes of rams were higher near the time of puberty. Accelerated growth followed by cessation of growth occurs concurrently with puberty in males of several species and is accompanied by an increase in the blood concentration of testosterone. Testosterone may mediate this accelerated growth by first increasing bone growth and then depleting the source of stem cells in the cartilage growth plate, the site where growth in length of long bones occurs.