Testicular expression of the Lin28/let-7 system: Hormonal regulation and changes during postnatal maturation and after manipulations of puberty

The Lin28/let-7 system, which includes the RNA-binding proteins, Lin28a/Lin28b, and let-7 miRNAs, has emerged as putative regulator of puberty and male gametogenesis; yet, its expression pattern and regulation in postnatal testis remain ill defined. We report herein expression profiles of Lin28 and let-7 members, and related mir-145 and mir-132, in rat testis during postnatal maturation and in models of altered puberty and hormonal deregulation. Neonatal expression of Lin28a and Lin28b was low and rose markedly during the infantile period; yet, expression patterns diverged thereafter, with persistently elevated levels only for Lin28b, which peaked at puberty. Let-7a, let-7b, mir-132 and mir-145 showed profiles opposite to Lin28b. In fact, let-7b and mir-145 were abundant in pachytene spermatocytes, but absent in elongating spermatids, where high expression of Lin28b was previously reported. Perturbation of puberty by neonatal estrogenization reverted the Lin28/let-7 expression ratio; expression changes were also detected in other models of delayed puberty, due to early photoperiod or nutritional manipulations. In addition, hypophysectomy or growth hormone (GH) deficiency revealed regulation of this system by gonadotropins and GH. Our data document the expression profiles of the Lin28/let-7 system in rat testis along postnatal/pubertal maturation, and their perturbation in models of pubertal and hormonal manipulation.