Increased testis growth and sperm production in adult rats following transient neonatal goitrogen treatment: optimization of the propylthiouracil dose and effects of methimazole
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Treatment of male rat pups with the reversible goitrogen 6-propyl-2-thiouracil (PTU), administered by adding 0.1% PTU to the mother's drinking water from birth to day 25, increases their testis size and daily sperm production (DSP) at 160 days of age by up to 80% and 140%, respectively. The purpose of this study was to examine the effectiveness of various concentrations of PTU and determine the PTU dose that would maximize testis growth while minimizing side effects such as decreased maternal water consumption and decreased pup growth. Whether this effect was specific to PTU was determined by evaluating the effects of another commonly used goitrogen, methimazole (MMI), in increasing adult testis size and sperm production. Dams were given PTU (0.1–0.0004% w/v) or 0.025% MMI (w/v) in their water from birth to day 25 post partum, then given no further treatment. Thyroxine concentrations were measured in all groups of pups at 25, 35 and 45 days, and testis weight and DSP were determined at 90 days of age. At 25 days of age, thyroxine concentrations were maximally decreased by PTU treatments of 0.0015% or greater; less severe decreases were produced by 0.0004% PTU or 0.025% MMI. Thyroxine concentrations increased in all treated groups at day 35 compared with day 25, and returned to normal by day 45. At 90 days of age, testis weight was increased by about 40% in rats whose mothers had been treated with doses of 0.006% PTU or greater, whereas testis weights in groups given 0.0015 and 0.0004% PTU or 0.025% MMI were increased 31, 15 and 18%, respectively. Similarly, DSP showed maximal increases at PTU doses of 0.006% or greater, whereas lower doses or MMI produced gradations of the maximal increase. At 90 days, body weights in the 0.1 and 0.025% PTU groups were reduced by approximately 25%. Despite the maximal increase in testis size and DSP, body weights in the 0.006% PTU group showed a smaller decrease (16%). Lower PTU doses produced smaller body weight decrements, and the body weight decrease in the MMI group (11%) was similar to that in the 0.0004% PTU group. In summary, a 0.006% PTU concentration is optimal for maximally increasing testicular growth and DSP at 90 days while minimizing side effects; lower concentrations of PTU (0.0015 and 0.0004% produce gradations of the maximal effect. Neonatal MMI administration was also effective in increasing adult testis size and DSP, although the potency of this drug is less than PTU and parallels its decreased potency compared with PTU in reducing thyroxine concentrations.
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