Biosynthesis of progesterone derived neurosteroids by developing avian CNS : In vitro effects on the gabaa receptor complex

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 Nervous System. However, there are scarcely any studies analyzing their production or their...

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Autores principales:	Pignataro, Leonardo Antonio, Colman Lerner, Alejandro Ariel, Barañao, José Lino S.
Publicado:	1998
Materias:	Chick optic lobe Developing avian CNS GABA(A) receptor complex Neurosteroidogenesis Neurosteroids [C]Progesterone [H]Flunitrazepam binding modulation 3beta hydroxy 5beta pregnan 20 one 4 aminobutyric acid A receptor carbon 14 flunitrazepam neurosteroid pregnanedione progesterone animal tissue article binding affinity biosynthesis central nervous system chicken controlled study embryo fowl nervous system development nonhuman optic lobe priority journal steroid metabolism steroidogenesis
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07365748_v16_n5_p433_Pignataro http://hdl.handle.net/20.500.12110/paper_07365748_v16_n5_p433_Pignataro
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paper:paper_07365748_v16_n5_p433_Pignataro2023-06-08T15:44:11Z Biosynthesis of progesterone derived neurosteroids by developing avian CNS : In vitro effects on the gabaa receptor complex Pignataro, Leonardo Antonio Colman Lerner, Alejandro Ariel Barañao, José Lino S. Chick optic lobe Developing avian CNS GABA(A) receptor complex Neurosteroidogenesis Neurosteroids [C]Progesterone [H]Flunitrazepam binding modulation 3beta hydroxy 5beta pregnan 20 one 4 aminobutyric acid A receptor carbon 14 flunitrazepam neurosteroid pregnanedione progesterone animal tissue article binding affinity biosynthesis central nervous system chicken controlled study embryo fowl nervous system development nonhuman optic lobe priority journal steroid metabolism steroidogenesis 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 Nervous System. However, there are scarcely any studies analyzing their production or their modulatory effects on this receptor during development. In this work, the biosynthesis of [C]progesterone metabolites as well as the characterization of their in vitro effects on the GABA(A) receptor complex in developing chick optic lobe were investigated. Studies on progesterone metabolism indicated that this steroid was converted to 5β-pregnanedione, 5β-pregan-3β-ol-20-one, and a 20-hydroxy derivative. Radioactive progesterone was completely metabolized at early embryonic stages, and a great proportion of 5β-pregnanedione was converted to 5β-pregnan-3β-ol-20-one. Thus, it seems that some of the steroidogenic activities present in chick optic lobe are age-dependent, though greater at embryonic stages. Results from in vitro modulation of [H]flunitrazepam binding by 5β-pregnan-3β-ol-20-one indicated that this steroid produces a one-component-concentration dependent enhancement above control binding. 5β-pregnan-3β-ol-20-one EC50 values were 0.195±0.049, 0.101±0.017, 0.147±0.009, and 0.569±0.114 μM, and E(max) were 22.37±1.57, 23.67±4.02, 29.01±1.08, and 15.11±2.67% at embryonic days 11, 14, hatching, and postnatal day 21, respectively.In conclusion, the biosynthesis of 5β-pregnan-3β-ol-20-one from progesterone in developing chick optic lobe, together with its ability to modulate the GABA(A) receptor present in such tissues, suggests a physiological role of this neurosteroid in developing avian Central Nervous System. Copyright (C) 1998 ISDN. Published by Elsevier Science Ltd. Fil:Pignataro, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Colman Lerner, A.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Barañao, J.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 1998 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07365748_v16_n5_p433_Pignataro http://hdl.handle.net/20.500.12110/paper_07365748_v16_n5_p433_Pignataro
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Chick optic lobe Developing avian CNS GABA(A) receptor complex Neurosteroidogenesis Neurosteroids [C]Progesterone [H]Flunitrazepam binding modulation 3beta hydroxy 5beta pregnan 20 one 4 aminobutyric acid A receptor carbon 14 flunitrazepam neurosteroid pregnanedione progesterone animal tissue article binding affinity biosynthesis central nervous system chicken controlled study embryo fowl nervous system development nonhuman optic lobe priority journal steroid metabolism steroidogenesis
spellingShingle	Chick optic lobe Developing avian CNS GABA(A) receptor complex Neurosteroidogenesis Neurosteroids [C]Progesterone [H]Flunitrazepam binding modulation 3beta hydroxy 5beta pregnan 20 one 4 aminobutyric acid A receptor carbon 14 flunitrazepam neurosteroid pregnanedione progesterone animal tissue article binding affinity biosynthesis central nervous system chicken controlled study embryo fowl nervous system development nonhuman optic lobe priority journal steroid metabolism steroidogenesis Pignataro, Leonardo Antonio Colman Lerner, Alejandro Ariel Barañao, José Lino S. Biosynthesis of progesterone derived neurosteroids by developing avian CNS : In vitro effects on the gabaa receptor complex
topic_facet	Chick optic lobe Developing avian CNS GABA(A) receptor complex Neurosteroidogenesis Neurosteroids [C]Progesterone [H]Flunitrazepam binding modulation 3beta hydroxy 5beta pregnan 20 one 4 aminobutyric acid A receptor carbon 14 flunitrazepam neurosteroid pregnanedione progesterone animal tissue article binding affinity biosynthesis central nervous system chicken controlled study embryo fowl nervous system development nonhuman optic lobe priority journal steroid metabolism steroidogenesis
description	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 Nervous System. However, there are scarcely any studies analyzing their production or their modulatory effects on this receptor during development. In this work, the biosynthesis of [C]progesterone metabolites as well as the characterization of their in vitro effects on the GABA(A) receptor complex in developing chick optic lobe were investigated. Studies on progesterone metabolism indicated that this steroid was converted to 5β-pregnanedione, 5β-pregan-3β-ol-20-one, and a 20-hydroxy derivative. Radioactive progesterone was completely metabolized at early embryonic stages, and a great proportion of 5β-pregnanedione was converted to 5β-pregnan-3β-ol-20-one. Thus, it seems that some of the steroidogenic activities present in chick optic lobe are age-dependent, though greater at embryonic stages. Results from in vitro modulation of [H]flunitrazepam binding by 5β-pregnan-3β-ol-20-one indicated that this steroid produces a one-component-concentration dependent enhancement above control binding. 5β-pregnan-3β-ol-20-one EC50 values were 0.195±0.049, 0.101±0.017, 0.147±0.009, and 0.569±0.114 μM, and E(max) were 22.37±1.57, 23.67±4.02, 29.01±1.08, and 15.11±2.67% at embryonic days 11, 14, hatching, and postnatal day 21, respectively.In conclusion, the biosynthesis of 5β-pregnan-3β-ol-20-one from progesterone in developing chick optic lobe, together with its ability to modulate the GABA(A) receptor present in such tissues, suggests a physiological role of this neurosteroid in developing avian Central Nervous System. Copyright (C) 1998 ISDN. Published by Elsevier Science Ltd.
author	Pignataro, Leonardo Antonio Colman Lerner, Alejandro Ariel Barañao, José Lino S.
author_facet	Pignataro, Leonardo Antonio Colman Lerner, Alejandro Ariel Barañao, José Lino S.
author_sort	Pignataro, Leonardo Antonio
title	Biosynthesis of progesterone derived neurosteroids by developing avian CNS : In vitro effects on the gabaa receptor complex
title_short	Biosynthesis of progesterone derived neurosteroids by developing avian CNS : In vitro effects on the gabaa receptor complex
title_full	Biosynthesis of progesterone derived neurosteroids by developing avian CNS : In vitro effects on the gabaa receptor complex
title_fullStr	Biosynthesis of progesterone derived neurosteroids by developing avian CNS : In vitro effects on the gabaa receptor complex
title_full_unstemmed	Biosynthesis of progesterone derived neurosteroids by developing avian CNS : In vitro effects on the gabaa receptor complex
title_sort	biosynthesis of progesterone derived neurosteroids by developing avian cns : in vitro effects on the gabaa receptor complex
publishDate	1998
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07365748_v16_n5_p433_Pignataro http://hdl.handle.net/20.500.12110/paper_07365748_v16_n5_p433_Pignataro
work_keys_str_mv	AT pignataroleonardoantonio biosynthesisofprogesteronederivedneurosteroidsbydevelopingaviancnsinvitroeffectsonthegabaareceptorcomplex AT colmanlerneralejandroariel biosynthesisofprogesteronederivedneurosteroidsbydevelopingaviancnsinvitroeffectsonthegabaareceptorcomplex AT baranaojoselinos biosynthesisofprogesteronederivedneurosteroidsbydevelopingaviancnsinvitroeffectsonthegabaareceptorcomplex
_version_	1768541993778020352

Biosynthesis of progesterone derived neurosteroids by developing avian CNS : In vitro effects on the gabaa receptor complex

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