Neurosteroids and CNS Development

Plasma levels of adrenal DHEA and DHEAS undergo dramatic developmental changes (38,39), suggesting that they may be involved in ontogeny. Ther role in brain development is implied by the experiments that showed that DHEA and DHEAS enhance neuronal and glial survival and differentiations in cultures from embryonic brains (40). Neurodevelopmental actions of DHEA(S) may be, in part, mediated via their actions at the GABAa receptors, whose subunit composition changes during fetal and neonatal development (8,9). In early embryonic and postnatal life, GABA acting via GABAA receptors depolarizes neurons from rat cortex, cerebellum, or spinal cord (41) and in immature neurons GABA stimulates chemokinesis (42), thereby facilitating neuronal migration. Because the "immature" GABAA receptors are modulated by the neurosteroids (15,44), an interplay between expression of distinct receptor subtypes manifesting different sensitivity to neurosteroids (15,44), and changing concentrations of neurosteroids in brains of the fetuses and neonates may sculpt neurodevelopmental processes. A role of DHEA in the development deserves special attention. This steroid appears to be synthesized in the CNS, because it was present in brains of adult rats even after adrenalectomy and gonadectomy (3), but the efforts to find the cytochrome P450c17, which has 17-hydroxylase-17,20-lyase activity (and which converts PREG to DHEA) in brains of adult rats were unsuccessful (45). Nonetheless, mRNA for P450c17 was detected in brains of rat embryos (46). The transient developmental presence of DHEA synthesizing enzyme in the embryonic brain, combined with striking developmental changes of DHEA levels in plasma, strongly suggest an important role of this hormone in CNS development. For example, the very high plasma concentration of DHEAS at birth in humans (39) may have an essential analeptic role during birth both for fetus and mother.

Pregnancy And Childbirth

Pregnancy And Childbirth

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