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
Betty FumelSophie FouchÉCourt

Abstract

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. 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 and Leydig cells using a novel aromatase-iCre (ARO-iCre) line that expresses Cre recombinase under control of the human Cyp19(IIa)/aromatase promoter. 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 TRαAMI specifically in Sertoli cells in order to investigate T3 regulation of steroidogenesis. We demonstrated that TRαAMI-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, TRαAMI-ARO males showed normal fertility. This phenotype is similar to TRαAMI-SC males...Continue Reading

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Citations

May 30, 2019·Journal of Clinical Medicine·Rosita A CondorelliAldo E Calogero
Jun 8, 2017·Frontiers in Physiology·Eddy RijntjesKatja J Teerds
Dec 14, 2018·Current Opinion in Endocrine and Metabolic Research·Arturo Hernandez

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