Ms. Viapiano et Sf. Deplazas, 3-BETA-OH-5-BETA-PREGNAN-20-ONE ENHANCES [H-3] GABA BINDING IN DEVELOPING CHICK OPTIC LOBE, Journal of receptor and signal transduction research, 17(4), 1997, pp. 585-597
The neurosteroids are synthesized in the CNS and act mainly through al
losteric modulation of the GABA(A) receptor. Structure-activity relati
onship studies in mammalian CNS have shown that a 3 alpha-hydroxyl gro
up and a 5 alpha-reduced A-ring are striking features for their biolog
ical activity, while the 3 beta, 5 beta structures as in 3 beta, 5 bet
a-P are completely inactive. In this work we report the enhancing acti
vity of epipregnanolone on [H-3]GABA binding to its receptor sites in
the chick optic lobe. Concentration-effect curves for this neurosteroi
d showed a concentration dependent activity with different potencies a
t the three developmental stages studied, the hatching stage being the
most sensitive to the steroid stimulatory effect. The displacement of
a potent 3 alpha, 5 alpha steroid by epipregnanolone indicated that t
his steroid behaved as a partial agonist of the steroid recognition si
te. Considering the developmental profile for steroidogenesis in avian
tissues and the biological relevance of 5 beta-reduced steroids in ea
rly development, we propose that 3 or its 3 alpha-epimer, pregnanolone
, instead of the potent 3 alpha, 5 alpha neurosteroids, modulates GABA
(A) receptors in the chick optic lobe during development.