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The effects of neonatal treatment with the reversible goitrogen, 6-n-propyl-2-thiouracil (PTU) on the volumes of testicular interstitial components, the number and average volume of Leydig cells, and the steroid secretory capacity of testis and Leydig cells of rats at 135 days of age were investigated. Rat pups were hypothyroid from birth to 25 days of age following the addition of 0.1% (w/v) PTU to the drinking water of the mother. Treatment was stopped at 25 days and the pups subsequently returned to a euthyroid state. Control rat pups were raised without adding PTU to drinking water of the mother. On day 135, one testis from each rat (n = 5 per group) was fixed by whole body perfusion for microscopy and stereology, and the ipsilateral testis was used for steroid secretion analysis using an in vitro testis perfusion system. Average testis volume was 84% greater in PTU-treated rats than in controls. This increase resulted from increases in both the seminiferous tubule (86%) and the interstitial (80%) volumes. Moreover, absolute volumes of all testis components in PTU-treated rats were significantly (P < 0.05) greater than those of controls; the highest volume increase was observed in the lymphatic space (147%). The number of Leydig cells per testis was nearly doubled, but the average volume of a Leydig cell was decreased by 25% in PTU-treated rats compared with controls. Steroid secretion per testis was not significantly different between control and PTU-treated rats; however, steroid secretion per Leydig cell was significantly lower in PTU-treated rats than in controls. These results demonstrate that the neonatal administration of PTU causes Leydig cell hyperplasia. However, the normal androgenic status of these animals is maintained by hypotrophy associated with reduced steroid secretion of individual Leydig cells at maturity.
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