Subunit-Specific Developmental Roles of PI3K in SF1- Expressing Cells

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Authors: My Khanh Q Huynh ; Sang Hee Lyoo ; Dong Joo Yang ; Yun-Hee Choi ; Ki Woo Kim

Citation: Endocrinology and Metabolism(대한내분비학회지), Vol.39(5) : 793-802, 2024-10

MeSH: Adrenal Cortex / metabolism ; Animals ; Class I Phosphatidylinositol 3-Kinases / genetics ; Class I Phosphatidylinositol 3-Kinases / metabolism ; Class Ia Phosphatidylinositol 3-Kinase / genetics ; Class Ia Phosphatidylinositol 3-Kinase / metabolism ; Female ; Male ; Mice ; Mice, Knockout* ; Ovary / metabolism ; Phosphatidylinositol 3-Kinases / metabolism ; RNA Splicing Factors ; Steroidogenic Factor 1* / genetics ; Steroidogenic Factor 1* / metabolism ; Testis / metabolism

Keywords: Development ; Phosphatidylinositol 3-kinase ; Steroidogenic factor 1 ; p110α ; p110β

Abstract: Backgruound: Phosphatidylinositol 3-kinase (PI3K) regulates cellular development and energy homeostasis. However, the roles of its subunits in organ development remain largely unknown.

Methods: We explored the roles of PI3K catalytic subunits in steroidogenic factor 1 (SF1)-expressing cells through knockout (KO) of the p110α and p110β subunits.

Results: We examined mice with a double KO of p110α and p110β in SF1-expressing cells (p110αβ KOSF1). Although these animals exhibited no significant changes in the development of the ventromedial hypothalamus, we noted pronounced hypotrophy in the adrenal cortex, testis, and ovary. Additionally, corticosterone and aldosterone levels were significantly reduced. The absence of these subunits also resulted in decreased body weight and survival rate, along with impaired glucose homeostasis, in p110αβ KOSF1 mice.

Conclusion: The data demonstrate the specific roles of PI3K catalytic subunits in the development and function of SF1-expressing organs.