The steroid hormones corticosterone and testosterone are supplied to the central nervous system by endocrine glands, the adrenals and gonads. In contrast, the 3 beta-hydroxy-delta 5-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-450scc, 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.
The cytochrome P-450(17 alpha)-hydroxylase, 17----20 lyase (P-450(17 alpha)) is the key enzyme responsible for the biosynthesis of androgens in steroidogenic organs. Its cellular localization has been examined with an immunohistochemical technique. In immature rat ovary, P-450(17 alpha) was first detected in sparse interstitial cells on postnatal Day 8. The number of immunoreactive interstitial cells increased thereafter and the intensity of P-450(17 alpha) staining in these cells was highest at 3 weeks of age. The intensity of staining then started to decline and was very faint at Day 35. From 6 weeks on, the distribution of immunoreactive P-450(17 alpha) was of the adult type: it was detected exclusively in the thecal cells of the large antral, preovulatory, follicles. P-450(17 alpha) was not detectable during pregnancy except on the day of parturition, when thecal cells were transiently immunoreactive. The staining had vanished 24 h after delivery. Human chorionic gonadotrophin (hCG), injected into immature females on Days 24 to 26, induced P-450(17 alpha) prematurely in thecal cells. When injected on Days 12 to 14 of pregnancy, hCG also induced P-450(17 alpha) in the thecal cells surrounding the largest follicles, whereas the interstitial and luteal cells were not immunostained. The antiprogestin RU486, injected on Day 16 of pregnancy, reinstated P-450(17 alpha) (and P-450scc) immunoreactivity in the thecal cells. Oestradiol selectively suppressed P-450(17 alpha) expression in the thecal cells of RU486-treated females. In immature guinea-pig ovary, P-450(17 alpha) was immunostained in thecal cells, not in interstitial cells, although the interstitial cells expressed the delta 5-3 beta-hydroxysteroid dehydrogenase. P-450(17 alpha) was also immunolocalized in the Leydig cells of rat and guinea-pig testes, and in the guinea-pig adrenal cortex (zonae fasciculata and reticularis), but not in the rat adrenal cortex. P-450(17 alpha) was not detectable in the brain of either rat or guinea-pig.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.