Effect of Inactivation of Mst1 and Mst2 in the Mouse Adrenal Cortex.

Autor:	Abou Nader N; Centre de Recherche en Reproduction et Fertilité, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe J2S 7C6, Canada., Blais É; Centre de Recherche en Reproduction et Fertilité, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe J2S 7C6, Canada., St-Jean G; Centre de Recherche en Reproduction et Fertilité, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe J2S 7C6, Canada., Boerboom D; Centre de Recherche en Reproduction et Fertilité, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe J2S 7C6, Canada., Zamberlam G; Centre de Recherche en Reproduction et Fertilité, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe J2S 7C6, Canada., Boyer A; Centre de Recherche en Reproduction et Fertilité, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe J2S 7C6, Canada.
Jazyk:	angličtina
Zdroj:	Journal of the Endocrine Society [J Endocr Soc] 2022 Sep 16; Vol. 7 (1), pp. bvac143. Date of Electronic Publication: 2022 Sep 16 (Print Publication: 2022).
DOI:	10.1210/jendso/bvac143
Abstrakt:	Recent conditional knockout of core components of the Hippo signaling pathway in the adrenal gland of mice has demonstrated that this pathway must be tightly regulated to ensure proper development and maintenance of the adrenal cortex. We report herein that the most upstream kinases of the pathway, the mammalian STE20-like protein kinases 1 and 2 (MST1and MST2, respectively), are expressed in the mouse adrenal cortex with MST2 expression being restricted to the zona glomerulosa (zG). To further explore the role of Hippo signaling in adrenocortical cells, we conditionally deleted Mst1/2 in steroidogenic cells using an Nr5a1-cre strain ( Mst1 flox/flox ; Mst2 flox/flox ; Nr5a1 -cre). Our results show that the loss of MST1/2 leads to the premature and progressive accumulation of subcapsular GATA4+, WT1+ adrenal gonadal primordium (AGP)-like progenitor cells starting at 2 months of age without affecting aldosterone and corticosterone secretion. To help us understand this phenotype, microarray analyses were performed on adrenal glands from 2-month-old mutant and control mice. Gene expression analyses revealed that loss of Mst1/2 leads to the overexpression of known downstream target genes ( Ajuba , Aqp1 , Fn1 , Ibsp , Igf1 , Igfbp2 , Mmp2 , Thbs1 ) of the main effector of Hippo signaling, YAP; and underexpression of genes ( Agtr1b , Ecgr4 , Hsd3b6 , Nr0b1 , Tesc , Vsnl1 ) that are normally specifically expressed in the zG or overexpressed in the zG compared to the zona fasciculata (zF). Together, these results suggest that MST1/2 regulates Hippo signaling activity in the adrenal cortex and that these two kinases are also involved in the fine tuning of zG cell function or differentiation. (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)
Databáze:	MEDLINE
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