3β-OH-5β-pregnan-20-one enhances [H]GABA binding in developing chick optic lobe
Journal of Receptor and Signal Transduction Research, ISSN: 1079-9893, Vol: 17, Issue: 4, Page: 585-597
1997
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Article Description
The neurosteroids are synthesized in the CNS and act mainly through allosteric modulation of the GABA(A) receptor. Structure-activity relationship studies in mammalian CNS have shown that a 3α-hydroxyl group and a 5α-reduced A-ring are striking features for their biological activity, while the 3β,5β structures as in 3β,5β-P are completely inactive. In this work we report the enhancing activity of epipregnanolone on [H]GABA binding to its receptor sites in the chick optic lobe. Concentration-effect curves for this neurosteroid showed a concentration-dependent activity with different potencies at the three developmental stages studied, the hatching stage being the most sensitive to the steroid stimulatory effect. The displacement of a potent 3α,5α steroid by epipregnanolone indicated that this steroid behaved as a partial agonist of the steroid recognition site. Considering the developmental profile for steroidogenesis in avian tissues and the biological relevance of 5β-reduced steroids in early development, we propose that 3 or its 3α-epimer, pregnanolone, instead of the potent 3α,5α neurosteroids, modulates GABA(A) receptors in the chick optic lobe during development.
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