Estrogenic compounds inhibit gap junctional intercellular communication in mouse Leydig TM3 cells

Area of Science:

• Endocrinology
• Cell Biology
• Toxicology

Background:

• Estrogenic compounds can disrupt testicular function by affecting Leydig cells.
• Gap junctional intercellular communication (GJIC) is crucial for maintaining homeostasis in Leydig cells during development and carcinogenesis.

Purpose of the Study:

• To investigate the effects of diethylstilbestrol (DES), 17beta-estradiol (E2), and genistein (GEN) on GJIC in mouse Leydig TM3 cells.
• To elucidate the mechanisms underlying the observed effects on GJIC.

Main Methods:

• Lucifer yellow microinjection was used to assess GJIC in mouse Leydig TM3 cells.
• Cells were treated with varying concentrations and time points of DES, E2, and GEN.
• The involvement of estrogen receptor (ER) and protein kinase C (PKC) was examined using specific inhibitors (ICI 182,780 and calphostin C).

Main Results:

• DES, E2, and GEN all inhibited GJIC in TM3 cells.
• DES exhibited sustained inhibition, while E2 and GEN showed rapid but less persistent inhibition.
• DES-induced inhibition was ER-dependent, whereas E2 and GEN involved both ER and PKC pathways.
• Combined effects and dose-dependent inhibition at near-physiological estrogen levels were observed for DES and E2.

Conclusions:

• Estrogenic compounds differentially affect GJIC in Leydig cells.
• DES acts primarily via the estrogen receptor, while E2 and GEN utilize both estrogen receptor and protein kinase C pathways.
• These distinct mechanisms may contribute to non-genotoxic effects of these compounds on testicular carcinogenesis and development.