Oestrogen regulates SOX9 bioavailability by rapidly activating ERK1/2 and stabilising microtubules in a human...

Area of Science:

• Endocrinology
• Developmental Biology
• Cell Biology

Background:

• Nuclear SOX9 is crucial for Sertoli cell differentiation and testis development.
• Oestrogen exposure leads to SOX9 cytoplasmic retention, inhibiting testis development and promoting ovarian development.
• SOX9 cytoplasmic localization depends on microtubule stability, influenced by the MAPK complex ERK1/2, which responds to oestrogen.

Purpose of the Study:

• To investigate the mechanism by which oestrogen promotes cytoplasmic retention of SOX9.
• To determine if oestrogen stabilizes microtubules through ERK1/2 activation to affect SOX9 localization.

Main Methods:

• Treatment of human testis-derived NT2/D1 cells with oestrogen.
• Assessment of ERK1/2 activation, microtubule network stability, and SOX9 localization.
• Use of the ERK1/2 inhibitor U0126 to block oestrogen's effects.

Main Results:

• Oestrogen rapidly activated ERK1/2, stabilized microtubules, and increased cytoplasmic SOX9 within 30 minutes.
• The ERK1/2 inhibitor U0126 blocked oestrogen-induced changes in SOX9 and tubulin.
• ERK1/2 mediates oestrogen's effects on microtubule stabilization and SOX9 cytoplasmic retention.

Conclusions:

• Oestrogen impacts MAPK signaling, specifically ERK1/2, to stabilize microtubules.
• This stabilization leads to cytoplasmic retention of SOX9, inhibiting its nuclear bioavailability.
• The findings reveal a novel mechanism by which oestrogen disrupts Sertoli cell differentiation and testis development.