DAPL1 is a novel regulator of testosterone production in Leydig cells of mouse testis

Leydig cells in the testes produce testosterone in the presence of gonadotropins. Therefore, male testosterone levels must oscillate within a healthy spectrum, given that elevated testosterone levels augment the risk of cardiovascular disorders. We observed that the expression of death-associated pr...

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Bibliographic Details
Published in:Scientific reports 2021-09, Vol.11 (1), p.18532-12, Article 18532
Main Authors: Chen, Hong-bin, Pineda Garcia, Jorge Carlos, Arizono, Shinako, Takeda, Tomoki, Li, Ren-shi, Hattori, Yukiko, Sano, Hiroe, Miyauchi, Yuu, Hirota, Yuko, Tanaka, Yoshitaka, Ishii, Yuji
Format: Article
Language:English
Subjects:
631/45/776/1174
631/45/776/812
Animals
Apoptosis
Cardiovascular diseases
Cell Line
Cyclic AMP response element-binding protein
Deregulation
Gene Deletion
Gonadotropins
Health risks
Humanities and Social Sciences
Kinases
Leydig cells
Leydig Cells - metabolism
Male
Mice
Mice, Inbred C57BL
multidisciplinary
Pituitary (anterior)
Protein kinase A
Proteins
Science
Science (multidisciplinary)
Steroidogenesis
Steroidogenic acute regulatory protein
Testes
Testis - metabolism
Testosterone
Testosterone - metabolism
Transcription
Tumor cells
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Summary:Leydig cells in the testes produce testosterone in the presence of gonadotropins. Therefore, male testosterone levels must oscillate within a healthy spectrum, given that elevated testosterone levels augment the risk of cardiovascular disorders. We observed that the expression of death-associated protein-like 1 (DAPL1), which is involved in the early stages of epithelial differentiation and apoptosis, is considerably higher in the testes of sexually mature mice than in other tissues. Accordingly, Dapl1 -null mice were constructed to evaluate this variation. Notably, in these mice, the testicular levels of steroidogenic acute regulatory protein (StAR) and serum testosterone levels were significantly elevated on postnatal day 49. The findings were confirmed in vitro using I-10 mouse testis-derived tumor cells. The in vivo and in vitro data revealed the DAPL1-regulated the expression of StAR involving altered transcription of critical proteins in the protein kinase A and CREB/CREM pathways in Leydig cells. The collective findings implicate DAPL1 as an important factor for steroidogenesis regulation, and DAPL1 deregulation may be related to high endogenous levels of testosterone.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-97961-6