Article (Scientific journals)
Multiple mechanisms control brain aromatase activity at the genomic and non-genomic level
Balthazart, Jacques; Baillien, Michelle; Charlier, Thierry et al.
2003In Journal of Steroid Biochemistry and Molecular Biology, 86, p. 367-379
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Keywords :
Estrogen synthase; Preoptic area; Sexual Behavior; Protein phosphorylations; Calcium; Glutamate receptors
Abstract :
[en] Evidence has recently accumulated indicating that aromatase activity in the preoptic area is modulated in parallel by both slow (hours to days) genomic and rapid (minutes to hours) non-genomic mechanisms. We review here these two types of control mechanisms and their potential contribution to various aspects of brain physiology in quail. High levels of aromatase mRNA, protein and activity (AA) are present in the preoptic area of this species where the transcription of aromatase is controlled mainly by steroids. Estrogens acting in synergy with androgens play a key role in this control and both androgen and estrogen receptors (ER; alpha and beta subtypes) are present in the preoptic area even if they are not necessarily co-localized in the same cells as aromatase. Steroids have more pronounced effects on aromatase transcription in males than in females and this sex difference could be caused, in part, by a sexually differentiated expression of the steroid receptor coactivator 1 in this area. The changes in aromatase concentration presumably control seasonal variations as well as sex differences in brain estrogen production. Aromatase activity in hypothalamic homogenates is also rapidly (within minutes) down-regulated by exposure to conditions that enhance protein phosphorylation such as the presence of high concentrations of calcium, magnesium and ATP. Similarly, pharmacological manipulations such as treatment with thapsigargin or stimulation of various neurotransmitter receptors (alpha-amino-3-hydroxy-methyl-4-isoxazole propionic acid (AMPA), kainate, and N-methyl-d-aspartate (NMDA)) leading to enhanced intracellular calcium concentrations depress within minutes the aromatase activity measured in quail preoptic explants. The effects of receptor stimulation are presumably direct: electrophysiological data confirm the presence of these receptors in the membrane of aromatase-expressing cells. Inhibitors of protein kinases interfere with these processes andWestern blotting experiments on brain aromatase purified by immunoprecipitation confirm that the phosphorylations regulating aromatase activity directly affect the enzyme rather than another regulatory protein. Accordingly, several phosphorylation consensus sites are present on the deduced amino acid sequence of the recently cloned quail aromatase. Fast changes in the local availability of estrogens in the brain can thus be caused by aromatase phosphorylation so that estrogen could rapidly regulate neuronal physiology and behavior. The rapid as well as slower processes of local estrogen production in the brain thus match well with the genomic and non-genomic actions of steroids in the brain. These two processes potentially provide sufficient temporal variation in the bio-availability of estrogens to support the entire range of established effects for this steroid.
Research center :
Centre de Neurobiologie Cellulaire et Moléculaire
Departement of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, MD, USA
Disciplines :
Neurosciences & behavior
Author, co-author :
Balthazart, Jacques  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau
Baillien, Michelle
Charlier, Thierry ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau
Cornil, Charlotte  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau
Ball, Gregory
Language :
English
Title :
Multiple mechanisms control brain aromatase activity at the genomic and non-genomic level
Publication date :
2003
Journal title :
Journal of Steroid Biochemistry and Molecular Biology
ISSN :
0960-0760
eISSN :
1879-1220
Publisher :
Pergamon Press, Oxford, United Kingdom
Volume :
86
Pages :
367-379
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
NIH - National Institutes of Health [US-MD] [US-MD]
FWB - Fédération Wallonie-Bruxelles [BE]
ULg FSR - Université de Liège. Fonds spéciaux pour la recherche [BE]
FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture [BE]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
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