Comparative aspects of neurosteroids: production and function

University of Central Lancashire / University of Liverpool (2002) J Physiol 543P, S333

Communications: Comparative aspects of neurosteroids: production and function

K. Tsutsui* and R.W. Lea

Department of Biological Sciences, University of Central Lancashire, Preston PR1 2HE, UK and *Laboratory of Brain Science, Faculty of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima, 739-8521, Japan

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The actions of peripheral steroid hormones upon the brain, crossing the bloodÐbrain barrier, are well known. Furthermore, the expression of specific receptors for such hormones have been localised in specific and discrete areas of the CNS in numerous species. Recently, evidence indicates that the brain itself, in addition to being a target tissue for steroids, may also have the ability to synthesize steroids de novo from cholesterol. Such steroids have been termed ‘neurosteroids’. The existence of such neurosteroids was first established in mammals (Baulieu, 1997) and the majority of related studies have been carried out using the rat as an animal model. Only limited studies have been performed so far on non-mammalian vertebrates. However, evidence is now accumulating that neurosteroid production by the brain is common throughout the vertebrate kingdom. Furthermore, although little is still understood regarding their physiological significance in these other vertebrates, some evidence now exists to suggest a number of possible associations with both early development and reproduction. For instance, in the amphibian brain, the amount of pregnenolone and pregnenolone sulphate together with steroidogenic enzymes such as cytochrome P450 side-chain cleavage, express significant changes over the year which may be related to the breeding cycle. Furthermore, in species such as the Xenopus, the concentration of pregnenolone in the brain is significantly higher than that in either the gonads or plasma. The existence of P450scc in these lower vertebrates is thus indicative of an early and conserved property of vertebrate brains. The existence of neurosteroids has also recently been demonstrated in birds. In the quail, biochemical analysis of progesterone metabolism indicates the brain may be involved in the active production of 5β-dihydroprogesterone from progesterone only during embryogenesis, perhaps indicating a role for this neurosteroid in neuronal development. In contrast, in the ring dove, a species in which both sexes share in the incubation of eggs and the care of the young, the in vitro incubation of sections of diencephalon with tritiated pregnenolone, in order to determine the rate of biosynthesis of progesterone, demonstrated a greater synthesis of progesterone in the brains of brooding male birds compared with non-breeding males (P < 0.05). Consistent with this is the observation that although circulating plasma progesterone levels are low during the brooding phase, progesterone concentrations in the brain of brooding male doves are higher compared with non-breeding birds (P < 0.05). The expression of parental behaviour in this species can be induced by progesterone and so these studies possibly provide a further functional significance for synthesis of progesterone in the dove brain.




Where applicable, experiments conform with Society ethical requirements.

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