INCREASED PROLIFERATION OF LEYDIG-CELLS INDUCED BY NEONATAL-HYPOTHYROIDISM IN THE RAT

Treatment of male rat pups with the reversible goitrogen 6-n-propyl-2- thiouracil (PTU), administered by adding 0.1% PTU to the mother's drin king water from birth through weaning, increases adult testis size, nu mber of Sertoli cells, and daily sperm production. Adult Leydig cell n umbers are also increased by 70%, despite permanent suppression of ser um luteinizing hormone (LH). The present study was designed to test wh ether this effect results from an increase in proliferation of Leydig cells or the mesenchymal precursors. The labeling indices (LI) of six interstitial cell types were measured by tritiated thymidine autoradio graphy. With the exception of Leydig cells, LI declined after birth fo r all interstitial cell types in both control and PTU-treated rats, bu t mesenchymal cell proliferation was not significantly different in co ntrol and treated rats. In contrast, the LI of Leydig cells from PTU-t reated rats rose by day 10, remained elevated through day 45 (highest on day 35 at 3.6-fold higher than control, P < 0.05), and declined to control values by day 50. The LI of Leydig cells in control rats was u nchanged during the experiment. Proliferating Leydig cells were immatu re, as shown by their cytoplasmic lipid droplets. Adult Leydig cells, which lack lipid droplets, did not proliferate. Mesenchymal and immatu re Leydig cells contained thyroid hormone receptor mRNA; levels in adu lt Leydig cells were reduced but detectable. In conclusion, proliferat ion of Leydig cells, rather than increased proliferation of their mese nchymal precursors, is the principal mechanism responsible for the inc rease in Leydig cell number after neonatal hypothyroidism. Increased L eydig cell proliferation could result from direct effects of hypothyro idism on these cells. Alternatively, the increased Sertoli cell popula tion that results from PTU treatment could also stimulate increased Le ydig cell proliferation, or both of these mechanisms could contribute to the Leydig cell increase.