Thyroid hormone inhibits the proliferation of piglet Sertoli cell via PI3K signaling pathway

Theriogenology. 2015 Jan 1;83(1):86-94. doi: 10.1016/j.theriogenology.2014.08.003. Epub 2014 Aug 10.

Abstract

Accumulating researches show that thyroid hormone (TH) inhibits Sertoli cells (SCs) proliferation and stimulates their functional maturation in prepubertal rat testis, confirming that TH plays a key role in testicular development. However, the mechanism under the T3 regulation of piglet SC proliferation remains unclear. In the present study, in order to investigate the possible mechanism of T3 on the suppression of SC proliferation, the expression pattern of TRα1 and cell cycle-related molecules, effect of T3 on SC proliferation, and the role of phosphoinositide 3-kinase (PI3K)/Akt signaling pathway on the T3-mediated SC proliferation in piglet testis were explored. Our results demonstrated that TRα1 was expressed in all tested stages of SCs and decreased along with the ages. T3 inhibited the proliferation of SCs in a time- and dose-dependent manner, and T3 treatment downregulated the expressions of cell cycling molecules, such as cyclinA2, cyclinD1, cyclinE1, PCNA, and Skp2, but upregulated the p27 expression in SCs. Most importantly, the suppressive effects of T3 on SC proliferation seemed dependent on the inhibition of PI3K/Akt signaling pathway, and pre-stimulation of PI3K could enhance such suppressive effects. Together, our findings demonstrate that TH inhibits the proliferation of piglet SCs via the suppression of PI3K/Akt signaling pathway.

Keywords: PI3K pathway; Piglet; Sertoli cell; Thyroid hormone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Male
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sertoli Cells / cytology
  • Sertoli Cells / drug effects*
  • Sertoli Cells / physiology
  • Signal Transduction / drug effects*
  • Swine / physiology*
  • Thyroid Hormone Receptors alpha / genetics
  • Thyroid Hormone Receptors alpha / metabolism
  • Thyroid Hormones / pharmacology*

Substances

  • RNA, Messenger
  • Thyroid Hormone Receptors alpha
  • Thyroid Hormones
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt