Ontogeny of the neurosteroid enzyme Cyp7b in the mouse

Bean, Rhona; Lathe, Richard; Martin, Cécile

doi:10.1016/s0303-7207(00)00443-3

Cited by 20 publications

(14 citation statements)

References 46 publications

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“…This is consistent with a previous finding that CYP7B1 is active in the brain only during early development. 49 Our data indicate that excessive amounts of 3bAdiol inhibit the normal control of expression of ERs suggesting that 3bAdiol has an important role in the regulation of ER expression during development. To our knowledge, animal models that show abnormally large, heavy brain are rare.…”

Section: Dynamics Of Estrogen Receptors In the Brain N Sugiyama Et Almentioning

confidence: 61%

Spatiotemporal dynamics of the expression of estrogen receptors in the postnatal mouse brain

Sugiyama

Andersson

Lathe³

et al. 2008

Mol Psychiatry

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This study reports on the spatiotemporal dynamics of the expression of estrogen receptors (ERs) in the mouse central nervous system (CNS) during the early postnatal and the peripubertal period. At postnatal day 7 (P7), neurons with strong nuclear immunostaining for both ERa and ERb1 were widely distributed throughout the brain. Sucrose density gradient sedimentation followed by western blotting supported the histochemical evidence for high levels of both ERs at P7. Over the following 2 days, there was a rapid downregulation of ERs. At P9, ERa expression was visible only in the hypothalamic area. Decline in ERb1 expression was slower than that of ERa, and ERa-negative, ERb1-positive cells were observed in the dentate gyrus and walls of third ventricle. Between P14 and P35, ERs were undetectable except for the hypothalamic area. As before P7, the ovary does not produce estrogen but does produce 5a-androstane-3b, 17b-diol (3bAdiol), an estrogenic metabolite of dihydrotestosterone, we examined the effects of high levels of 3bAdiol in the postnatal period. We used CYP7B1 knockout mice which cannot hydroxylate and inactivate 3bAdiol. The brains of these mice are abnormally large with reduced apoptosis. In the early postnatal period, there was 1-week delay in the timing of the reduction in ER expression in the brain. These data reveal that the time when ERs might be activated in the brain is limited to the first 8 postnatal days. In addition, the importance of aromatase has to be reconsidered as the alternative estrogen, 3bAdiol, is important in neuronal function in the postnatal brain.

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Section: Dynamics Of Estrogen Receptors In the Brain N Sugiyama Et Almentioning

confidence: 61%

Spatiotemporal dynamics of the expression of estrogen receptors in the postnatal mouse brain

Sugiyama

Andersson

Lathe³

et al. 2008

Mol Psychiatry

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“…In Cyp7b1 2 /2 mice, DHEA hydroxylation is abolished in the brain, prostate, and other tissues [99]. Interestingly, Cyp7b1 mRNA and activity are widely expressed during ontogeny, but shows more restricted expression in the hippocampus in newborn mice [100]. CYP7B1 is highly active in hydroxylation of DHEA to 7a-hydroxyDHEA.…”

Section: Cyp7b1mentioning

confidence: 99%

Regulation of bile acid synthesis: pathways, nuclear receptors, and mechanisms

Chiang

2004

Journal of Hepatology

466

344

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“…Decreased hippocampal CYP7B bioactivity is therefore not an inevitable consequence of aging. A previous study also reported somewhat lower 7␣-hydroxylation of PREG and DHEA by mouse brain microsomes with age (Doostzadeh and Morfin, 1996), albeit the oldest mice tested were only 10 months old, less than half their lifespan, and these were compared with 2-monthold juveniles [CYP7B expression in hippocampus shows a complex ontogeny (Bean et al, 2001)]. Hippocampal PREG levels decline with age and correlate with cognitive impairments in rats , suggesting that both the substrate for CYP7B and the enzyme itself may decline in a subset of aged rodents with cognitive deficits.…”

Section: Discussionmentioning

confidence: 90%

Central Administration of a Cytochrome P450-7B Product 7α-Hydroxypregnenolone Improves Spatial Memory Retention in Cognitively Impaired Aged Rats

Yau¹,

Noble²,

Graham³

2006

J. Neurosci.

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Pregnenolone (PREG) and dehydroepiandrosterone (DHEA) have been reported to improve memory in aged rodents. In brain, these neurosteroids are transformed predominantly into 7␣-hydroxylated metabolites by the cytochrome P450-7B1 (CYP7B). The biological role of steroid B-ring hydroxylation is unclear. It has been proposed to generate bioactive derivatives that enhance cognition, immune, and other physiological processes. In support, 7␣-hydroxylated DHEA increases the immune response in mice with greater potency than the parent steroid. Whether the memory-enhancing effects of PREG in rats is mediated via its 7␣-hydroxylated metabolite 7␣-hydroxyPREG is not known. We investigated this by treating memory-impaired aged rats (identified by their spatial memory performances in the Morris water maze task compared with young controls) with 7␣-hydroxyPREG or PREG administered intracerebroventricularly using osmotic minipumps and then tested the rats during week 2 of steroid treatment in the eight-arm radial-arm version of the water maze (RAWM) that allows repeated assessment of learning. CYP7B bioactivity in hippocampal tissue (percentage conversion of [ 14 C]DHEA to [ 14 C]7␣-hydroxyDHEA) was decreased selectively in memory-impaired aged rats compared with both young and memory-intact aged rats. 7␣-hydroxyPREG (100 ng/h) but not PREG (100 ng/h) administration to memory-impaired aged rats for 11 d enhanced spatial memory retention (after a 30 min delay between an exposure trial 1 and test trial 2) in the RAWM. These data provide evidence for a biologically active enzyme product 7␣-hydroxyPREG and suggests that reduced CYP7B function in the hippocampus of memory-impaired aged rats may, in part, be overcome by administration of 7␣-hydroxyPREG.

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Ontogeny of the neurosteroid enzyme Cyp7b in the mouse

Cited by 20 publications

References 46 publications

Spatiotemporal dynamics of the expression of estrogen receptors in the postnatal mouse brain

Spatiotemporal dynamics of the expression of estrogen receptors in the postnatal mouse brain

Regulation of bile acid synthesis: pathways, nuclear receptors, and mechanisms

Central Administration of a Cytochrome P450-7B Product 7α-Hydroxypregnenolone Improves Spatial Memory Retention in Cognitively Impaired Aged Rats

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