Syce1 and Syce3 regulate testosterone and dihydrotestosterone synthesis via steroidogenic pathways in mouse Sertoli...

Testosterone (T) and dihydrotestosterone (DHT) are the main hormones regulating reproduction and development of male animals. Although their synthesis and secretion are regulated by the endocrine system [hypothalamic-pituitary-gonadal (adrenal) axis], it is also possible to synthesize T and DHT from the induction of two proteins: Syce1 and Syce3. As central elements of the synaptonemal complex (SC), Syce1 and Syce3 play a key role in the association of homologous chromosomes during meiosis. However, Syce1 and Syce3 also promote the synthesis of T and DHT, although potential mechanisms have yet to be revealed. In this study, Leydig and Sertoli cells, which are responsible for the production and regulation of steroid hormones in testis, were transfected with recombinant Syce1/Syce3 and silence sequence. Our results revealed the highest expression of Syce1 and Syce3 in spermatogenic cells of the testis. Moreover, overexpression or knockdown of Syce1 and Syce3 in Sertoli and Leydig cells resulted in activation or suppression of steroidogenic genes Star and Hsd3b, which are involved in a steroidogenic pathway that upregulates T synthesis. Upregulated expression of Syce1 resulted in a significant increase in Srd5a1, which can promote DHT secretion. Interestingly, Syce1 and Syce3 overexpression synergistically promoted each other's abundance. Our results define a previously unknown mechanism of Syce1 and Syce3 dependent activation of steroidogenic signaling in Sertoli and Leydig cells.