Development of the adult-type Leydig cell population in the rat is affected by neonatal thyroid hormone levels

We have investigated the effects of neonatal-prepubertal changes in thyroid hormone levels on the early phases of adult-type Leydig cell development in the rat testis. Hypothyroidism was induced by adding 6-propyl-2-thiouracil (PTU) to the drinking water, while hyperthyroidism was induced by daily injections with triiodothyronine (T3). The proliferative activity of the Leydig cells in PTU-treated animals was not different from that in age-matched controls through the age of 16 days. Nevertheless, the percentage of Leydig cells (i.e., the proportion of Leydig cells among the total interstitial cell population) was approximately 83% and 67% lower at the ages of 12 and 16 days, respectively. The proliferative activity of the Leydig cells in the T3-treated animals compared to the controls was increased approximately 3-fold at the ages of 12 and 16 days. The percentage of Leydig cells in T3-treated animals was also considerably increased at these two ages (400% and 725%, respectively). Concomitantly, the percentage of peritubular cells was decreased, suggesting that the increase in the percentage of Leydig cells may at least partially be the result of differentiation of peritubularly located precursor cells. Plasma testosterone levels fluctuated considerably at these ages. Hence, injection of T3 during the neonatal-prepubertal period not only affects Sertoli cell proliferation and differentiation but also directly or indirectly affects the onset of the formation of the adult-type Leydig cell population and its functio

Depletion of the p43 Mitochondrial T3 Receptor Increases Sertoli Cell Proliferation in Mice

Among T3 receptors, TRα1 is ubiquitous and its deletion or a specific expression of a dominant-negative TRα1 isoform in Sertoli cell leads to an increase in testis weight and sperm production. The identification of a 43-kDa truncated form of the nuclear receptor TRα1 (p43) in the mitochondrial matrix led us to test the hypothesis that this mitochondrial transcription factor could regulate Sertoli cell proliferation. Here we report that p43 depletion in mice increases testis weight and sperm reserve. In addition, we found that p43 deletion increases Sertoli cell proliferation in postnatal testis at 3 days of development. Electron microscopy studies evidence an alteration of mitochondrial morphology observed specifically in Sertoli cells of p43-/- mice. Moreover, gene expression studies indicate that the lack of p43 in testis induced an alteration of the mitochondrial-nuclear cross-talk. In particular, the up-regulation of Cdk4 and c-myc pathway in p43-/- probably explain the extended proliferation recorded in Sertoli cells of these mice. Our finding suggests that T3 limits post-natal Sertoli cell proliferation mainly through its mitochondrial T3 receptor p43