Dataset Information
Expression of dominant-negative thyroid hormone receptor alpha1 in Leydig and Sertoli cells demonstrates no additional defect compared with expression in Sertoli cells only.
Ontology highlight
ABSTRACT: Background
In the testis, thyroid hormone (T3) regulates the number of gametes produced through its action on Sertoli cell proliferation. However, the role of T3 in the regulation of steroidogenesis is still controversial.Methods
The TR?AMI knock-in allele allows the generation of transgenic mice expressing a dominant-negative TR?1 (thyroid receptor ?1) isoform restricted to specific target cells after Cre-loxP recombination. Here, we introduced this mutant allele in both Sertoli and Leydig cells using a novel aromatase-iCre (ARO-iCre) line that expresses Cre recombinase under control of the human Cyp19(IIa)/aromatase promoter.Findings
We showed that loxP recombination induced by this ARO-iCre is restricted to male and female gonads, and is effective in Sertoli and Leydig cells, but not in germ cells. We compared this model with the previous introduction of TR?AMI specifically in Sertoli cells in order to investigate T3 regulation of steroidogenesis. We demonstrated that TR?AMI-ARO males exhibited increased testis weight, increased sperm reserve in adulthood correlated to an increased proliferative index at P3 in vivo, and a loss of T3-response in vitro. Nevertheless, TR?AMI-ARO males showed normal fertility. This phenotype is similar to TR?AMI-SC males. Importantly, plasma testosterone and luteinizing hormone levels, as well as mRNA levels of steroidogenesis enzymes StAR, Cyp11a1 and Cyp17a1 were not affected in TR?AMI-ARO.Conclusions/significance
We concluded that the presence of a mutant TR?AMI allele in both Leydig and Sertoli cells does not accentuate the phenotype in comparison with its presence in Sertoli cells only. This suggests that direct T3 regulation of steroidogenesis through TR?1 is moderate in Leydig cells, and that Sertoli cells are the main target of T3 action in the testis.
SUBMITTER: Fumel B
PROVIDER: S-EPMC4368620 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
Publications
Expression of dominant-negative thyroid hormone receptor alpha1 in Leydig and Sertoli cells demonstrates no additional defect compared with expression in Sertoli cells only.
PloS one 20150320 3
<h4>Background</h4>In the testis, thyroid hormone (T3) regulates the number of gametes produced through its action on Sertoli cell proliferation. However, the role of T3 in the regulation of steroidogenesis is still controversial.<h4>Methods</h4>The TRαAMI knock-in allele allows the generation of transgenic mice expressing a dominant-negative TRα1 (thyroid receptor α1) isoform restricted to specific target cells after Cre-loxP recombination. Here, we introduced this mutant allele in both Sertoli ...[more]
