Neurosteroids: Cytochrome P-450 _scc in Rat Brain

TLDR

Corticosterone and testosterone reach the brain from endocrine glands, whereas pregnenolone and dehydroepiandrosterone accumulate in rat brain through mechanisms independent of peripheral sources. Immunohistochemistry using antibodies against bovine adrenal cytochrome P‑450 scc, the enzyme that cleaves cholesterol side chains to form pregnenolone, was performed. The enzyme was found throughout white matter and in sparse clusters in the entorhinal, cingulate cortex, and olfactory bulb, supporting the existence of neurosteroids.

Abstract

The steroid hormones corticosterone and testosterone are supplied to the central nervous system by endocrine glands, the adrenals and gonads. In contrast, the 3β-hydroxy-Δ5-derivatives of cholesterol, pregnenolone and dehydroepiandrosterone, accumulate in the rat brain through mechanisms independent of peripheral sources. Immunohistochemical studies have been performed with specific antibodies to bovine adrenal cytochrome P-450 scc , which is involved in cholesterol side-chain cleavage and pregnenolone formation. The enzyme was localized in the white matter throughout the brain. Scarce clusters of cell bodies were also stained in the entorhinal and cingulate cortex and in the olfactory bulb. These observations strongly support the existence of "neurosteroids," which have been posited on the basis of biochemical, physiological, and behavioral studies.