Neurosteroids in rat sciatic nerves and Schwann cells

Area of Science:

• Neuroscience
• Endocrinology
• Cell Biology

Background:

• Pregnenolone (PREG) and corticosterone levels were investigated in rat sciatic nerves and plasma.
• Steroid concentrations varied between nerve tissue and plasma, with PREG being higher in nerves.

Purpose of the Study:

• To investigate the local synthesis and metabolism of pregnenolone (PREG) in peripheral nerves.
• To determine if PREG synthesis is dependent on glandular sources like testes or adrenal glands.
• To explore the role of Schwann cells in PREG production and transformation.

Main Methods:

• Radioimmunoassays were used to quantify PREG and corticosterone in rat sciatic nerves and plasma.
• Surgical manipulation (castration and adrenalectomy) was performed to assess steroid source dependency.
• Schwann cells were cultured to study their capacity for PREG synthesis and metabolism from precursors and their response to insulin and forskolin.

Main Results:

• PREG concentrations were significantly higher in sciatic nerves than in plasma.
• Unlike corticosterone, PREG levels remained unaffected by castration and adrenalectomy, indicating local synthesis.
• Cultured Schwann cells demonstrated the ability to synthesize PREG from 25-hydroxy-cholesterol.
• Schwann cells also converted PREG and dehydroepiandrosterone into specific hydroxylated metabolites and androstenediol.
• Steroid metabolism in Schwann cells was enhanced by insulin and forskolin.

Conclusions:

• Pregnenolone is synthesized locally within the sciatic nerve, independent of testicular or adrenal glands.
• Schwann cells are key players in the local production and metabolism of pregnenolone in peripheral nerves.
• These findings suggest a potential role for locally synthesized pregnenolone in peripheral nerve regeneration processes.