| First Author | Leal LF | Year | 2021 |
| Journal | Mol Cell Endocrinol | Volume | 522 |
| Pages | 111117 | PubMed ID | 33338547 |
| Mgi Jnum | J:302971 | Mgi Id | MGI:6510779 |
| Doi | 10.1016/j.mce.2020.111117 | Citation | Leal LF, et al. (2021) Pde8b haploinsufficiency in mice is associated with modest adrenal defects, impaired steroidogenesis, and male infertility, unaltered by concurrent PKA or Wnt activation. Mol Cell Endocrinol 522:111117 |
| abstractText | PDE8B, PRKAR1A and the Wnt/beta-catenin signaling are involved in endocrine disorders. However, how PDEB8B interacts with both Wnt and protein kinase A (PKA) signaling in vivo remains unknown. We created a novel Pde8b knockout mouse line (Pde8b(-/-)); Pde8b haploinsufficient (Pde8b(+/)(-)) mice were then crossed with mice harboring: (1) constitutive beta-catenin activation (Pde8b(+/)(-);DeltaCat) and (2) Prkar1a haploinsufficieny (Pde8b(+/)(-);Prkar1a(+/)(-)). Adrenals and testes from mice (3-12-mo) were evaluated in addition to plasma corticosterone, aldosterone and Dkk3 concentrations, and the examination of expression of steroidogenesis-, Wnt- and cAMP/PKA-related genes. Pde8b(-/-) male mice were infertile with down-regulation of the Wnt/beta-catenin pathway which did not change significantly in the Pde8b(+/)(-);DeltaCat mice. Prkar1a haploinsufficiency also did not change the phenotype significantly. In vitro studies showed that PDE8B knockdown upregulated the Wnt pathway and increased proliferation in CTNNB1-mutant cells, whereas it downregulated the Wnt pathway in PRKAR1A-mutant cells. These data support an overall weak, if any, role for PDE8B in adrenocortical tumorigenesis, even when co-altered with Wnt signaling or PKA upregulation; on the other hand, PDE8B appears to play a significant role in male fertility. |
