Article

Effect of estrogen and inhibition of phosphatidylinositol-3 kinase on Akt and FOXO1 in rat uterus.

Institute of Physiology, Pécs University Medical School, Szigeti út 12, Pécs H7624, Hungary.
Steroids (impact factor: 2.83). 06/2007; 72(5):422-8. DOI:10.1016/j.steroids.2007.03.001 pp.422-8
Source: PubMed

ABSTRACT The importance of FOXO transcription factors in regulating different aspects of cellular homeostasis and apoptosis has become apparent. Akt/protein kinase B has been shown to phosphorylate and inactivate members of FOXO family of transcription factors. Akt and its upstream regulator, phosphatidylinositol-3 kinase (PI3K) are involved in rapid action of estrogen (E2) in different cells and tissues. The aim of the present study was to analyze the E2/PI3K/Akt/FOXO pathway in rat uterus. In response to E2, phosphorylation of Akt/PKB on Ser473 and FOXO1 on Ser256 and Thr24 residues increased but with distinct kinetics, regulating the activation and inactivation of Akt and FOXO1 proteins, respectively. The antiestrogen ICI 182,780 prevented E2 induced Akt activation suggesting that estrogen receptors mediate this effect of E2. Intrauterine injection of Wortmannin caused a decrease in the phosphorylation of Ser473 of Akt, and attenuated phosphorylation of its downstream target FOXO1 at Ser256 and at Thr24. However, the effect of E2 on phosphorylation of Thr24 showed a kinetic pattern distinct from that of Ser256. Our results suggest that the E2/PI3K/Akt/FOXO1 pathway in rat uterus is functioning even at the lack of ovarian hormones and responses to E2 treatment. Estradiol increases Akt phosphorylation through a Wortmannin sensitive way, presumably involving PI3K. The present work shows that PI3K plays a crucial role in the phosphorylation and inactivation of FOXO1 in vivo, indicating that the regulation of this transcription factor is a more complex event in uterine cells requiring further investigations.

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    Article: Inhibition of the progesterone nuclear receptor during the bone linear growth phase increases peak bone mass in female mice.
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    [show abstract] [hide abstract]
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    PLoS ONE 01/2010; 5(7):e11410. · 4.09 Impact Factor
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Keywords

Akt/protein kinase B
 
attenuated phosphorylation
 
complex event
 
crucial role
 
distinct kinetics
 
downstream target FOXO1
 
E2 induced Akt activation
 
E2/PI3K/Akt/FOXO pathway
 
E2/PI3K/Akt/FOXO1 pathway
 
Estradiol increases Akt phosphorylation
 
estrogen receptors
 
FOXO family
 
FOXO transcription factors
 
kinetic pattern distinct
 
rapid action
 
rat uterus
 
regulating different aspects
 
Thr24 residues
 
transcription factors
 
Wortmannin sensitive way
 

Ferenc Lengyel