L. Pignataro et al., BIOSYNTHESIS OF PROGESTERONE DERIVED NEUROSTEROIDS BY DEVELOPING AVIAN CNS - IN-VITRO EFFECTS ON THE GABA(A) RECEPTOR COMPLEX, International journal of developmental neuroscience, 16(5), 1998, pp. 433-441
It has been demonstrated in different vertebrate species that the GABA
(A) receptor complex is modulated by certain steroids. Theses results
prompted work on the synthesis of these neurosteroids in the Central N
ervous System. However, there are scarcely any studies analyzing their
production or their modulatory effects on this receptor during develo
pment. In this work, the biosynthesis of [C-14]progesterone metabolite
s as weil as the characterization of their in vitro effects on the GAB
A, receptor complex in developing chick optic lobe were investigated.
Studies on progesterone metabolism indicated that this steroid was con
verted to 5 beta-pregnanedione, 5 beta-pregan-3 beta-ol-20-one. and a
20-hydroxy derivative. Radio-active progesterone was completely metabo
lized at early embryonic stages, and a great proportion of 5 beta-preg
nanedione was converted to 5 beta-pregnan-3 beta-ol-20-one. Thus, it s
eems that some of the steroidogenic activities present in chick optic
lobe are age-dependent, though greater at embryonic stages. Results fr
om ill vitro modulation of [H-3]flunitrazepam binding by 5 beta-preena
n-3 beta-ol-20-one indicated that this steroid produces a one-componen
t-concentration dependent enhancement above control binding. 5 beta-pr
egnan-3 beta-ol-20-one EC50 values were 0.195 +/- 0.049, 0.101 +/- 0.0
17, 0.147 +/- 0.009, and 0.569 +/- 0.114 mu M, and E-max were 22.37 +/
- 1.57, 23.67 +/- 4.02, 29.01 +/- 1.08, and 15.11 +/- 2.67% at embryon
ic days 11, 14, hatching, and postnatal day 21, respectively. In concl
usion, the biosynthesis of 5 beta-pregnan-3 beta-ol-20-one from proges
terone in developing chick optic lobe. together with its ability to mo
dulate the GABA(A) receptor present in such tissues, suggests a physio
logical role of this neurosteroid in developing avian Central Nervous
System. (C) 1998 ISDN. Published by Elsevier Science Ltd.