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CREBZF regulates testosterone production in mouse Leydig cells.

Minjie Lu1,2, Ruixue Zhang1,2, Tong Yu1,2

  • 1College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.

Journal of Cellular Physiology
|May 25, 2019
PubMed
Summary

CREBZF (CREB binding protein zinc finger) is crucial for testosterone production in mouse Leydig cells. This study shows CREBZF promotes hCG-induced testosterone synthesis by regulating key steroidogenic genes.

Keywords:
CREBZFmouse Leydig cellnuclear receptorsteroidogenic genestestosterone

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Area of Science:

  • Endocrinology
  • Molecular Biology
  • Reproductive Biology

Background:

  • CREBZF, a transcriptional coregulator, has known roles in various nuclear receptor functions.
  • Previous research indicated SMILE (long isoform of CREBZF) expression in the mouse uterus, upregulated by estrogen.
  • The role of CREBZF in testicular function remained largely unexplored.

Purpose of the Study:

  • To investigate the expression and function of CREBZF in mouse Leydig cells.
  • To determine CREBZF's role in regulating testosterone synthesis.
  • To elucidate the molecular mechanisms underlying CREBZF's action in Leydig cells.

Main Methods:

  • Analysis of CREBZF expression in mouse testes during sexual maturation.
  • CREBZF silencing using shRNA in primary Leydig cells and MLTC-1 cells.
  • Assessment of testosterone production and expression of steroidogenic genes (P450c17, 17β-HSD, 3β-HSD) after hCG stimulation.
  • Overexpression studies to confirm CREBZF's effects.
  • Measurement of Nr4a1 and Nr5a1 mRNA levels.

Main Results:

  • CREBZF expression was age-dependent and specific to Leydig cells during sexual maturation, with SMILE being the dominant isoform.
  • CREBZF silencing significantly inhibited hCG-stimulated testosterone production in vitro and in vivo.
  • CREBZF silencing reduced the expression of key steroidogenic genes (P450c17, 17β-HSD, 3β-HSD) following hCG stimulation.
  • CREBZF upregulated the expression of Nr4a1 and Nr5a1, essential for steroidogenic gene expression.

Conclusions:

  • CREBZF plays a significant role in promoting testosterone production in mouse Leydig cells.
  • CREBZF facilitates hCG-induced testosterone synthesis by modulating Nr4a1 and Nr5a1 expression.
  • CREBZF is a key regulator of testicular testosterone synthesis, impacting steroidogenic gene expression.