Prolonged and transient neonatal hypothyroidism on Leydig cell differentiation in the postnatal rat testis.

Hypothyroidism arrests the differentiation of adult Leydig cells (ALC) in the neonatal rat testis, and transient neonatal hypothyroidism produces a two-fold increase in the ALC numbers in the adult rat testis. We investigated 1) whether prolonged hypothyroidism beyond the neonatal period could continue to arrest the differentiation of the ALC, and 2) to understand how a two-fold increase in the number of ALC is produced in adult rats subjected to transient neonatal hypothyroidism. Three groups of Sprague Dawley rats were used; control, PTU-water group (transiently hypothyroid; added 0.1% propyl thiouracil/PTU to drinking water of lactating mothers at parturition until weaning of pups at day 21, pups were fed regular water thereafter), and PTU group (prolonged hypothyroid; mothers were fed 0.1% PTU in drinking water from parturition until pups were sacrificed at days 28 and 40 (pups had access to solid food after 21 days). Findings showed that PTU treatment continued to arrest ALC differentiation. Withdrawal of the PTU treatment at 21 days resulted in ALC differentiation by two-fold in number in PTU-water rats. Findings on luteinizing hormone (LH)-stimulated androgen secretory capacity per testis in vitro agreed with the morphological data. These results confirmed that 1) thyroid hormone is crucial to the onset of ALC differentiation in the postnatal rat testis, 2) increased numbers of mesenchymal cells present in the hypothyroid testes differentiate into ALC upon withdrawal of the PTU treatment to produce a two-fold number of ALC in adult rats subjected to transient neonatal hypothyroidism (i.e., PTU-water treatment), and 3) numbers of ALC and mesenchymal cells increase with age at a rate of 2:1 during the process of ALC differentiation in testes of control and PTU-water rats.