Selective deletion of Pten in theca-interstitial cells leads to androgen excess and ovarian dysfunction in mice

作者：Lan, Zi-Jian; Krause, M. S.; Redding, S. D.; Li, X.; Wu, G. Z.; Zhou, H. X.; Bohler, H. C.; Ko, C.; Cooney, A. J.; Zhou, Junmei; Lei, Z. M.^*

来源：Molecular and Cellular Endocrinology, 2017, 444(C): 26-37.

DOI：10.1016/j.mce.2017.01.043

• Pten
• Ovary theca cells
• Conditional knockout
• PI3K
• LHCGR
• PCOS

Theca cell-selective Pten mutation (tPtenMT) in mice resulted in increases in PDK1 and Akt phosphorylation, indicating an over-activation of PI3K signaling in the ovaries. These mice displayed elevated androgen levels, ovary enlargement, antral follicle accumulation, early fertility loss and increased expression of Lhcgr and genes that are crucial to androgenesis. These abnormalities were partially reversed by treatments of PI3K or Akt inhibitor. LH actions in Pten deficient theca cells were potentiated. The phosphorylation of Foxol was increased, while the binding of Foxo1 to forkhead response elements in the Lhcgr promoter was reduced in tPtenMT theca cells, implying a mechanism by which PI3K/Aktinduced upregulation of Lhcgr in theca cells might be mediated by reducing the inhibitory effect of Foxol on the Lhcgr promoter. The phenotype of tPtenMT females is reminiscent of human PCOS and suggests that dysregulated PI3K cascade in theca cells may be involved in certain types of PCOS pathogenesis.

• 出版日期2017-3-15
• 单位上海交通大学