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, 2021 02 15.
Article
em En
| MEDLINE
| ID: mdl-33338547
ABSTRACT
PDE8B, PRKAR1A and the Wnt/ß-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+/-;ΔCat) 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/ß-catenin pathway which did not change significantly in the Pde8b+/-;ΔCat 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.
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Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Esteroides
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Glândulas Suprarrenais
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Proteínas Quinases Dependentes de AMP Cíclico
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3',5'-AMP Cíclico Fosfodiesterases
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Proteínas Wnt
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Haploinsuficiência
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Infertilidade Masculina
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Cell Endocrinol
Ano de publicação:
2021
Tipo de documento:
Article