Ontogeny and regulation of variant thyroid hormone receptor isoforms in developing rat testis

Abstract

High affinity-low capacity nuclear triiodothyronine (T3) receptors (TRs), identified as a product of c-erbAalpha proto-oncogene, are expressed in prepubertal rat Sertoli cell. At this age, exogenous T3 treatment as well as hypothyroidism affects Sertoli cell functions. We examined the ontogenetic expression pattern of TRs in the rat testis. Northern analysis confirms that TRs are expressed at high level from fetal development until prepubertal period. RNase protection analysis demonstrates that TRalpha2, the variant isoform of TRalpha1, is constitutively expressed at all ages, while TRalpha3 is absent in the adult gonad. While TRalpha1 and TRalpha2 expression declines during development, Rev-erbAalpha (Rev), the antisense mRNA encoded by the same c-erbAalpha genomic locus, increases beginning 5 days after birth and maximizing in adulthood. TRalpha1, TRalpha2, and Rev mRNAs do not appear to be directly regulated by thyroid hormone in testis; however, short-term neonatal hypothyroidism leads to the expression of TRalpha1 and its variant in adult testis, which is absent in control coeval animals. Thus, during development of rat testis, the levels of messages of genes encoded in the c-erbAalpha. genomic locus have different ontogenetic control. The ontogenetic profile of TRalpha1 and its variant isoforms within the seminiferous epithelium suggests that these receptors are involved in the differentiation of the male gonad.

Rapid signal transduction in Sertoli cells

“…Sertoli cell function has received much attention since the finding of functional T 3 receptor expression in prepubertal testes. An ontogenetic pattern of TRa 1 and TRa 2 expression and of b mRNA receptor has been demonstrated in Sertoli cells (78,79). This allows the use of the testis as a naturally occurring model for studying the role of TR in the modulation of gene expression and cellular function in vivo (73,79).…”

Thyroid Hormones: Their Role in Testicular Steroidogenesis

“…Palmero et al [80] and Jannini et al [46] demonstrated high-affinity and low-capacity TR in fetal, neonatal, and prepubertal rat Sertoli cells. These authors showed that the presence of TR in the testis is very high in fetal and neonatal rats and that TR levels decrease in prepubertal rats to eventually become undetectable in adult animals [44][45][46][47]. They also suggest that Sertoli cells are the only testicular cells that contain TR, suggesting that they are the only targets for T3 action in the testis.…”

“…Jannini et al [44,45,47] claimed that age-dependent expression of TRa1, TRa2, and TRa3 is present in the testis, whereas TRb is completely absent in both human and rat testis. Some immunohistochemical and mRNA expression studies claim otherwise; they found that rat and pig testis contain TRb [21,33,56,77,87,93,94].…”

Propylthiouracil-induced congenital hypothyroidism upregulates vimentin phosphorylation and depletes antioxidant defenses in immature rat testis

“…TH receptors are highly expressed in neonatal Sertoli cells, indicating that the developing Sertoli cells and testis may be important TH targets (Jannini et al 1999, Rao et al 2003. In this context, Jannini et al (1995) and provided strong evidence that THs regulate Sertoli cell proliferation and differentiation in the neonatal testis.…”