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

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

Research output: Contribution to journalArticle

Abstract

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 Foxo1 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/Akt-induced upregulation of Lhcgr in theca cells might be mediated by reducing the inhibitory effect of Foxo1 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.

Original languageEnglish (US)
Pages (from-to)26-37
Number of pages12
JournalMolecular and Cellular Endocrinology
Volume444
DOIs
StatePublished - Mar 15 2017

Fingerprint

Theca Cells
Phosphatidylinositol 3-Kinases
Androgens
Phosphorylation
Response Elements
Mutation
Ovary
Genes
Chemical activation
Fertility
Up-Regulation
Phenotype
Gene Expression

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

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

In: Molecular and Cellular Endocrinology, Vol. 444, 15.03.2017, p. 26-37.

Research output: Contribution to journalArticle

Lan, ZJ, Krause, MS, Redding, SD, Li, X, Wu, GZ, Zhou, HX, Bohler, HC, Ko, C, Cooney, AJ, Zhou, J & Lei, ZM 2017, 'Selective deletion of Pten in theca-interstitial cells leads to androgen excess and ovarian dysfunction in mice', Molecular and Cellular Endocrinology, vol. 444, pp. 26-37. https://doi.org/10.1016/j.mce.2017.01.043
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. / Selective deletion of Pten in theca-interstitial cells leads to androgen excess and ovarian dysfunction in mice. In: Molecular and Cellular Endocrinology. 2017 ; Vol. 444. pp. 26-37.
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AU - Zhou, H. X.

AU - Bohler, H. C.

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AU - Lei, Z. M.

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