The effect of midazolam on mouse Leydig cell steroidogenesis and apoptosis

Edmund Cheung So, Ya Ting Chang, Chung-Hsi Hsing, Paul Wai Fung Poon, Sew Fen Leu, Bu Miin Huang

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The peripheral-type benzodiazepine receptor (PBR), a putative receptor in Leydig cells, modulates steroidogenesis. Since benzodiazepines are commonly used in regional anesthesia, their peripheral effects need to be defined. Therefore, this study set out to investigate in vitro effects of the benzodiazepine midazolam (MDZ) on Leydig cell steroidogenesis, and the possible underlying mechanisms. The effects of MDZ on steroidogenesis in primary mouse Leydig cells and MA-10 Leydig tumor cells were determined by radioimmunoassay. PBR, P450scc, 3β-HSD and StAR protein expression induced by MDZ was determined by Western blotting. Inhibitors of the signal transduction pathway and a MDZ antagonist were used to investigate the intracellular cascades activated by MDZ. In both cell types, MDZ-stimulated steroidogenesis in dose- and time-dependent manners, and induced the expression of PBR and StAR proteins, but had no effect on P450scc and 3β-HSD expressions. Moreover, H89 (PKA inhibitor) and GF109203X (PKC inhibitor) attenuated MDZ-stimulated steroid production. Interestingly, the MDZ antagonist (flumazenil) did not decrease MDZ-induced steroid production in both cell types. These results highly indicated that MDZ-induced steroidogenesis in mouse Leydig cells via PKA and PKC pathways, along with the expression of PBR and StAR proteins. In addition, MDZ at high dosages induced rounding-up, membrane blebbing, and then death in MA-10 cells. In conclusion, midazolam could induce Leydig tumor cell steroidogenesis, and high dose of midazolam could induce apoptosis in Leydig tumor cells.

Original languageEnglish
Pages (from-to)169-178
Number of pages10
JournalToxicology Letters
Volume192
Issue number2
DOIs
Publication statusPublished - Feb 1 2010
Externally publishedYes

Fingerprint

Leydig Cells
Midazolam
Apoptosis
GABA-A Receptors
Leydig Cell Tumor
Tumors
Cells
Benzodiazepines
Steroids
Flumazenil
Signal transduction
Proteins
Conduction Anesthesia
Blister
Radioimmunoassay
Signal Transduction
Western Blotting

Keywords

  • 3β-HSD
  • Cell death
  • Flumazenil (Anexate)
  • Leydig cell
  • Midazolam (Dormicum)
  • P450scc
  • PBR
  • PKA
  • PKC
  • StAR
  • Steroidogenesis

ASJC Scopus subject areas

  • Toxicology

Cite this

So, E. C., Chang, Y. T., Hsing, C-H., Poon, P. W. F., Leu, S. F., & Huang, B. M. (2010). The effect of midazolam on mouse Leydig cell steroidogenesis and apoptosis. Toxicology Letters, 192(2), 169-178. https://doi.org/10.1016/j.toxlet.2009.10.017

The effect of midazolam on mouse Leydig cell steroidogenesis and apoptosis. / So, Edmund Cheung; Chang, Ya Ting; Hsing, Chung-Hsi; Poon, Paul Wai Fung; Leu, Sew Fen; Huang, Bu Miin.

In: Toxicology Letters, Vol. 192, No. 2, 01.02.2010, p. 169-178.

Research output: Contribution to journalArticle

So, EC, Chang, YT, Hsing, C-H, Poon, PWF, Leu, SF & Huang, BM 2010, 'The effect of midazolam on mouse Leydig cell steroidogenesis and apoptosis', Toxicology Letters, vol. 192, no. 2, pp. 169-178. https://doi.org/10.1016/j.toxlet.2009.10.017
So, Edmund Cheung ; Chang, Ya Ting ; Hsing, Chung-Hsi ; Poon, Paul Wai Fung ; Leu, Sew Fen ; Huang, Bu Miin. / The effect of midazolam on mouse Leydig cell steroidogenesis and apoptosis. In: Toxicology Letters. 2010 ; Vol. 192, No. 2. pp. 169-178.
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