Dose-dependent and sequence-sensitive effects of amyloid-β peptide on neurosteroidogenesis in human neuroblastoma cells

Interactions between neurosteroidogenesis and proteins involved in age-related diseases are unknown. High concentrations of amyloid-β (Aβ) peptides induce plaques in Alzheimer's disease but several studies demonstrated that physiological or non-toxic doses are neuroprotective. We compared the effects of non-toxic and toxic concentrations of Aβ1–42 and Aβ25–35 on neurosteroidogenesis in human neuroblastoma SH-SY5Y cells. Viability assays revealed that nanomolar doses of Aβ are devoid of cytotoxicity while 12 μM induced cell death. Pulse-chase, high-performance liquid chromatography and flow-scintillation analyses showed that non-toxic Aβ1–42 concentrations, acting selectively, decreased [3H]progesterone but increased [3H]estradiol production from the precursor [3H]pregnenolone. Non-toxic Aβ25–35 doses reduced [3H]progesterone formation but had no effect on [3H]estradiol biosynthesis. At 12 μM, both Aβ1–42 and Aβ25–35 inhibited [3H]progesterone formation but only Aβ1–42 reduced [3H]estradiol production. The results demonstrate a selective and amino-acid sequence-dependent action of Aβ on neurosteroidogenesis. The fact that non-toxic Aβ1–42 doses stimulated neuroprotective-neurosteroid estradiol synthesis, which is inhibited by high Aβ1–42 doses, may explain Aβ1–42 ability to exert either protective or deleterious effects on nerve cells.