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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Pde8b haploinsufficiency in mice is associated with modest adrenal defects, impaired steroidogenesis, and male infertility, unaltered by concurrent PKA or Wnt activation

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Leal, Leticia Ferro [1, 2, 3, 4] ; Szarek, Eva [4] ; Berthon, Annabel [4] ; Nesterova, Maria [4] ; Faucz, Fabio R. [4] ; London, Edra [4] ; Mercier, Christopher [4] ; Abu-Asab, Mones [4] ; Starost, Matthew F. [5] ; Dye, Louis [6] ; Bilinska, Barbara [7] ; Kotula-Balak, Malgorzata [8] ; Antonini, Sonir R. [1] ; Stratakis, Constantine A. [4]
Total Authors: 14
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pediat, BR-14049900 Sao Paulo - Brazil
[2] Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos - Brazil
[3] Dr Paulo Prata FACISB, Barretos Sch Hlth Sci, Barretos - Brazil
[4] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet PDEGEN, NIH, Bethesda, MD 20892 - USA
[5] NIH, Div Vet Resources, Bethesda, MD 20892 - USA
[6] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Microscopy & Imaging Core, NIH, Bethesda, MD 20892 - USA
[7] Jagiellonian Univ Krakow, Inst Zool, Dept Endocrinol, Krakow - Poland
[8] Agr Univ Krakow, Univ Ctr Vet Med, Krakow - Poland
Total Affiliations: 8
Document type: Journal article
Source: Molecular and Cellular Endocrinology; v. 522, FEB 15 2021.
Web of Science Citations: 0

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(+/)(-);Delta Cat) 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(+/-);Delta Cat mice. Prkarla 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 PRKAR1Amutant 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. (AU)

FAPESP's process: 13/05337-3 - The interaction between Wnt canonical pathway with PRKAR1A and PDE8B in adrenocortical tumor development and/or progression by using a transgenic mouse model
Grantee:Letícia Ferro Leal
Support Opportunities: Scholarships abroad - Research Internship - Doctorate