Artículo

Liu, A.; Margaill, I.; Zhang, S.; Labombarda, F.; Coqueran, B.; Delespierre, B.; Liere, P.; Marchand-Leroux, C.; O'Malley, B.W.; Lydon, J.P.; De Nicola, A.F.; Sitruk-Ware, R.; Mattern, C.; Plotkine, M.; Schumacher, M.; Guennoun, R. "Progesterone receptors: A key for neuroprotection in experimental stroke" (2012) Endocrinology. 153(8):3747-3757
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Abstract:

Progesterone receptors (PR) are expressed throughout the brain. However, their functional significance remains understudied. Here we report a novel role of PR as crucial mediators of neuroprotection using a model of transient middle cerebral artery occlusion and PR knockout mice. Six hours after ischemia, we observed a rapid increase in progesterone and 5α-dihydroprogesterone, the endogenous PR ligands, a process that may be a part of the natural neuroprotective mechanisms. PR deficiency, and even haploinsufficiency, increases the susceptibility of the brain to stroke damage. Within a time window of 24 h, PR-dependent signaling of endogenous brain progesterone limits the extent of tissue damage and the impairment of motor functions. Longer-term improvement requires additional treatment with exogenous progesterone and is also PR dependent. The potent and selective PR agonist Nestorone is also effective. In contrast to progesterone, levels of the neurosteroid allopregnanolone, which modulates γ-aminobutyric acid type A receptors, did not increase after stroke, but its administration protected both wild-type and PR-deficient mice against ischemic damage. These results show that 1) PR are linked to signaling pathways that influence susceptibility to stroke, and 2) PR are direct key targets for both endogenous neuroprotection and for therapeutic strategies after stroke, and they suggest a novel indication for synthetic progestins already validated for contraception. Although allopregnanolone may not be an endogenous neuroprotective agent, its administration protects the brain against ischemicdamageby signaling mechanisms not involving PR. Collectively, our data clarify the relative roles of PR and allopregnanolone in neuroprotection after stroke. Copyright © 2012 by The Endocrine Society.

Registro:

Documento: Artículo
Título:Progesterone receptors: A key for neuroprotection in experimental stroke
Autor:Liu, A.; Margaill, I.; Zhang, S.; Labombarda, F.; Coqueran, B.; Delespierre, B.; Liere, P.; Marchand-Leroux, C.; O'Malley, B.W.; Lydon, J.P.; De Nicola, A.F.; Sitruk-Ware, R.; Mattern, C.; Plotkine, M.; Schumacher, M.; Guennoun, R.
Filiación:Unité Mixte de Recherche 788, Institut National de la Santé et de la Recherche Médicale, University Paris-Sud, 80, rue du Général Leclerc, 94276 Kremlin-Bicêtre, France
EA4475 Pharmacologie de la Circulation Cérébrale, University Paris Descartes, 75006 Paris, France
Instituto de Biologia Y Medicina Experimental, Department of Human Biochemistry, University of Buenos Aires, 1428 Buenos Aires, Argentina
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, United States
Center for Biomedical Research, Population Council, Rockefeller University, New York, NY 10065, United States
M et P Pharma AG, CH-6370 Stans, Switzerland
Palabras clave:3alpha hydroxy 5alpha pregnan 20 one; 4 aminobutyric acid; 5alpha pregnane 3,20 dione; elcometrine; progesterone; progesterone receptor; animal experiment; animal model; animal tissue; article; controlled study; disease predisposition; gene inactivation; haploinsufficiency; hypoxic ischemic encephalopathy; middle cerebral artery occlusion; motor dysfunction; mouse; neuroprotection; nonhuman; priority journal; signal transduction; stroke; Animals; Brain; Male; Mice; Mice, Knockout; Norprogesterones; Pregnanolone; Progesterone; Receptors, Progesterone; Signal Transduction; Stroke
Año:2012
Volumen:153
Número:8
Página de inicio:3747
Página de fin:3757
DOI: http://dx.doi.org/10.1210/en.2012-1138
Título revista:Endocrinology
Título revista abreviado:Endocrinology
ISSN:00137227
CODEN:ENDOA
CAS:3alpha hydroxy 5alpha pregnan 20 one, 516-54-1; 4 aminobutyric acid, 28805-76-7, 56-12-2; 5alpha pregnane 3,20 dione, 566-65-4; elcometrine, 7759-35-5; progesterone, 57-83-0; Norprogesterones; Pregnanolone, 128-20-1; Progesterone, 57-83-0; Receptors, Progesterone; ST 1435, 7759-35-5
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00137227_v153_n8_p3747_Liu

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Citas:

---------- APA ----------
Liu, A., Margaill, I., Zhang, S., Labombarda, F., Coqueran, B., Delespierre, B., Liere, P.,..., Guennoun, R. (2012) . Progesterone receptors: A key for neuroprotection in experimental stroke. Endocrinology, 153(8), 3747-3757.
http://dx.doi.org/10.1210/en.2012-1138
---------- CHICAGO ----------
Liu, A., Margaill, I., Zhang, S., Labombarda, F., Coqueran, B., Delespierre, B., et al. "Progesterone receptors: A key for neuroprotection in experimental stroke" . Endocrinology 153, no. 8 (2012) : 3747-3757.
http://dx.doi.org/10.1210/en.2012-1138
---------- MLA ----------
Liu, A., Margaill, I., Zhang, S., Labombarda, F., Coqueran, B., Delespierre, B., et al. "Progesterone receptors: A key for neuroprotection in experimental stroke" . Endocrinology, vol. 153, no. 8, 2012, pp. 3747-3757.
http://dx.doi.org/10.1210/en.2012-1138
---------- VANCOUVER ----------
Liu, A., Margaill, I., Zhang, S., Labombarda, F., Coqueran, B., Delespierre, B., et al. Progesterone receptors: A key for neuroprotection in experimental stroke. Endocrinology. 2012;153(8):3747-3757.
http://dx.doi.org/10.1210/en.2012-1138