Early hypothyroidism in rats causes increased adult testis and reproductive organ size but does not change testosterone levels

Abstract

The role of thyroid hormones in the testis is unclear, although recent evidence indicates they may be important for testicular development. Here we describe a novel method for increasing adult testicular size in the rat by induction of transient hypothyroidism during neonatal life. Rats were treated with a reversible goitrogen, 6-propyl-2-thiouracil from birth to day 25 when treatment was stopped, allowing return to a euthyroid state. At days 90, 135, 160, and 180, wt and DNA content of the testis, epididymis, ventral prostate, seminal vesicle, and those of some nonreproductive organs were determined, as well as serum levels of testosterone (T) and thyroid hormones. Despite decreased body wts in 90-day and older 6-propyl-2-thiouracil-treated rats, testis wt was increased by 40% and 60% at 90 and 135 days, respectively; maximal increase (80%) occurred at 160 days. These wt increases were accompanied by proportional changes in DNA content. Significant enlargements were also seen in other reproductive organs, but they occurred after a time lag and were smaller in magnitude. Interestingly, serum T levels showed no increase at any age. Weight and DNA content of nonreproductive organs, like body wts, were less than controls at all ages but thyroid hormone levels were normal. Thus, transient hypothyroidism in neonatal rats is associated with lasting enlargements in the ultimate size of testis and other reproductive organs in the adult. These changes are not related to excess T levels. The results indicate early critical influences of thyroid hormones on growth and development of the reproductive system and suggest an experimental model for inducing lasting enlargements in testis and reproductive organs. The model may also be useful for studying regulation of reproductive growth and final size.