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???displayArticle.abstract??? Cytochrome P450aromatase (P450arom; aromatase) is a microsomal enzyme involved in the production of endogeneous sex steroids by converting testosterone (T) into oestradiol (E2). Aromatase is the product of the cyp19a1 gene and plays a crucial role in the sexual differentiation of the brain and in the regulation of reproductive functions. In the brain of mammals and birds, expression of cyp19a1 has been evidenced essentially in neuronal populations of the telencephalon and diencephalon. In contrast, a wealth of evidence established that in teleost fishes, aromatase expression in the brain is restricted to radial glial cells. The current study investigated the precise neuroanatomical distribution of cyp19a1 mRNA during brain development in Xenopus laevis (late embryonic to juvenile stages). For this purpose, we used in situ hybridization alone or combined with the detection of a proliferative (PCNA), glial (BLBP, Vimentin) or neuronal (Acetyl-tub; HuC/D; NeuroβTubulin) markers. We provide evidence that cyp19a1 expression in the brain is initiated from very early larval stage and remains strongly detected until juvenile and adult stages. At all stages analysed, we found the highest expression of cyp19a1 in the preoptic area and the hypothalamus as compared to the rest of the brain. In these two brain regions, cyp19a1-positive cells were never detected in the ventricular layers. Indeed, no co-labelling could be observed with radial glial (BLBP, Vimentin) or dividing progenitors (PCNA) markers. On the contrary, cyp19a1-positive cells perfectly matched with the distribution of post-mitotic neurones as shown by the use of specific markers (HuC/D, Acetyl-tub and Neuroβtubulin). These data suggest that, similar to what was found in other tetrapods, aromatase in the brain of amphibians is found in post-mitotic neurones and not in radial glia as reported in teleosts. This article is protected by copyright. All rights reserved.
Figure 1. Expression pattern of cyp19a1 (CYP) (a1–f1 and a2–f2) compared to Vimentin (VIM) (a3–f3) in the Xenopus laevis prometamorphic larva (NF stage 58) brain. Top: dorsal view of the X. laevis brain. Letters correspond to the rostrocaudal location of transverse sections as depicted in the whole brain drawing. Illustrations (a2) to (f2) correspond to higher magnifications of (a1) to (f1) and to adjacent sections of (a3) to (f3). Arrows and arrowheads highlight less conspicuous areas of labelling. For all images, dorsal is to the top. Scale bars = 100 μm.
Figure 2. Expression pattern of cyp19a1 (CYP) (g1âk1 and g2âk2) compared to Vimentin (VIM) (g3âk3) in the Xenopus laevis prometamorphic larva (NF stage 58) brain. Letters correspond to the rostrocaudal location of transverse sections as depicted in the whole brain drawing of Fig.1. Illustrations (g2) to (k2) correspond to higher magnifications of (g1) to (k1) and to adjacent sections of (g3) to (k3). (lân) Control in situ hybridisation experiments using cyp19a1 sense (m) or antisense (l and n) probes on X. laevis (l and m) or Xenopus tropicalis transverse sections. For all images, dorsal is to the top. Scale bars = 100 μm.
Figure 3. Distribution of cyp19a1 (CYP) transcripts at different brain developmental stages. In situ hybridisations for cyp19a1 at late embryonic stage 42 (NF42; a, b); at premetamorphic stages NF47 (c, d), NF49 (e, f) and NF52 (g, h); and at prometamorphic NF58 (i, j), metamorphic NF62 (k, l) and post-metamorphic NF66 (juvenile; m, n) stages. For all developmental stages, transverse sections at the levels of the preoptic area (POA) (a, c, e, g, i, k, m) and hypothalamus (b, d, f, h, j, l, n) are shown. Arrows highlight less conspicuous areas of labelling. (lân) For all images, dorsal is to the top. Scale bars = 100 μm.
Figure 4. Cyp19a1/brain lipid binding protein (BLBP) and Cyp19a1 (CYP)/proliferating cell nuclear antigen (PCNA) double-stainings in the preoptic and hypothalamic areas of metamorphic (NF62) brain. Transverse sections at the level of the preoptic area (aâi) or hypothalamus (jâr). Arrows in (a) and (j) indicate the precise location of the high magnifications illustrations (bâi) and (kâr), respectively. In situ hybridisation using a cyp19a1 probe (CYP) combined with BLBP (b, e, f, k, n, o) or PCNA (c, h, i, l, q, r) immunohistochemistry. To allow a merge with the 4â,6-diamidino-2-phenylindole (DAPI) staining, colours of BLBP and PCNA immunostainings in (b), (c), (k) and (l) are changed. Asterisks in (k), (n) and (o) indicate background labelling. For all images, dorsal is to the top. Scale bar = 100 μm in (a) and (j); 50 μm in (bâi) and (kâr).
Figure 5. Cyp19a1 transcripts distribution compared to several neuronal markers on juvenile (aâc) and adult (dâf) preoptic area transverse sections. (aâc) Cyp19a1 (CYP) in situ hybridisations (a, c) combined with acetylated tubulin (TUB) immunodetections (b, c). Arrows indicate some double-stained cells. (dâf) Comparison between Cyp19a1 (CYP) in situ hybridisation (d), HuC/D immunodetection (HU) and Neuroβtubulin (NβT) in situ hybridisation on adjacent sections. For all images, dorsal is to the top. Scale bar = 50 μm.
Abdelgadir,
Distribution of aromatase cytochrome P450 messenger ribonucleic acid in adult rhesus monkey brains.
1997, Pubmed
Abdelgadir,
Distribution of aromatase cytochrome P450 messenger ribonucleic acid in adult rhesus monkey brains.
1997,
Pubmed
Ball,
Hormonal regulation of brain circuits mediating male sexual behavior in birds.
2004,
Pubmed
Balthazart,
Distribution of aromatase-immunoreactive cells in the mouse forebrain.
1991,
Pubmed
Balthazart,
Estradiol, a key endocrine signal in the sexual differentiation and activation of reproductive behavior in quail.
2009,
Pubmed
Balthazart,
Distribution of aromatase in the brain of the Japanese quail, ring dove, and zebra finch: an immunocytochemical study.
1990,
Pubmed
Balthazart,
New insights into the regulation and function of brain estrogen synthase (aromatase).
1998,
Pubmed
Beaujean,
Immunocytochemical localization and biological activity of hydroxysteroid sulfotransferase in the frog brain.
1999,
Pubmed
Berg,
Xenopus tropicalis as a test system for developmental and reproductive toxicity.
2009,
Pubmed
,
Xenbase
Burrone,
Induced synthesis of P450 aromatase and 17β-estradiol by D-aspartate in frog brain.
2012,
Pubmed
Callard,
Phylogenetic distribution of aromatase and other androgen-converting enzymes in the central nervous system.
1978,
Pubmed
Callard,
Identification of aromatase in the reptilian brain.
1977,
Pubmed
Carswell,
Brain aromatase expression after experimental stroke: topography and time course.
2005,
Pubmed
Chu,
The appearance of acetylated alpha-tubulin during early development and cellular differentiation in Xenopus.
1989,
Pubmed
,
Xenbase
Cohen,
Aromatase mRNA in the brain of adult green anole lizards: effects of sex and season.
2011,
Pubmed
Coumailleau,
Sim1 and Sim2 expression during chick and mouse limb development.
2009,
Pubmed
Dalla Valle,
European sea bass (Dicentrarchus labrax L.) cytochrome P450arom: cDNA cloning, expression and genomic organization.
2002,
Pubmed
D'Amico,
The neurogenic factor NeuroD1 is expressed in post-mitotic cells during juvenile and adult Xenopus neurogenesis and not in progenitor or radial glial cells.
2013,
Pubmed
,
Xenbase
D'Amico,
Proliferation, migration and differentiation in juvenile and adult Xenopus laevis brains.
2011,
Pubmed
,
Xenbase
Dias,
Steroidogenic enzyme gene expression in the brain of the parthenogenetic whiptail lizard, Cnemidophorus uniparens.
2009,
Pubmed
Diotel,
Aromatase in the brain of teleost fish: expression, regulation and putative functions.
2010,
Pubmed
Endo,
Brain regeneration in anuran amphibians.
2007,
Pubmed
,
Xenbase
Ever,
Radial 'glial' progenitors: neurogenesis and signaling.
2005,
Pubmed
Evrard,
Immunocytochemical localization of aromatase in sensory and integrating nuclei of the hindbrain in Japanese quail (Coturnix japonica).
2004,
Pubmed
Foidart,
Aromatase-immunoreactive cells in the quail brain: effects of testosterone and sex dimorphism.
1994,
Pubmed
Forlano,
Anatomical distribution and cellular basis for high levels of aromatase activity in the brain of teleost fish: aromatase enzyme and mRNA expression identify glia as source.
2001,
Pubmed
Forlano,
Brain aromatase: new lessons from non-mammalian model systems.
2006,
Pubmed
Fornaro,
Neuron-specific Hu proteins sub-cellular localization in primary sensory neurons.
2007,
Pubmed
Fusani,
Hormonal influence on song structure and organization: the role of estrogen.
2006,
Pubmed
Garcia-Segura,
Aromatase in the brain: not just for reproduction anymore.
2008,
Pubmed
Garcia-Segura,
Aromatase expression by astrocytes after brain injury: implications for local estrogen formation in brain repair.
1999,
Pubmed
Gelinas,
Immunolocalization of aromatase- and androgen receptor-positive neurons in the goldfish brain.
1997,
Pubmed
Gohin,
Aromatase expression in Xenopus oocytes: a three cell-type model for the ovarian estradiol synthesis.
2011,
Pubmed
,
Xenbase
Goto-Kazeto,
Localization and expression of aromatase mRNA in adult zebrafish.
2004,
Pubmed
Götz,
Radial glial cells defined and major intermediates between embryonic stem cells and CNS neurons.
2005,
Pubmed
Gravagna,
Localization of Kv2.2 protein in Xenopus laevis embryos and tadpoles.
2008,
Pubmed
,
Xenbase
Guerriero,
Estrogen receptors and aromatase activity in the hypothalamus of the female frog, Rana esculenta. Fluctuations throughout the reproductive cycle.
2000,
Pubmed
Hutchison,
Brain aromatization of testosterone in the male Syrian hamster: effects of androgen and photoperiod.
1991,
Pubmed
Iwabuchi,
Analysis of the p450 aromatase gene expression in the Xenopus brain and gonad.
2007,
Pubmed
,
Xenbase
Iwabuchi,
Expression profile of the aromatase enzyme in the Xenopus brain and localization of estradiol and estrogen receptors in each tissue.
2013,
Pubmed
,
Xenbase
Kallivretaki,
The zebrafish, brain-specific, aromatase cyp19a2 is neither expressed nor distributed in a sexually dimorphic manner during sexual differentiation.
2007,
Pubmed
Kiyota,
The POU homeobox protein Oct-1 regulates radial glia formation downstream of Notch signaling.
2008,
Pubmed
,
Xenbase
Kloas,
Endocrine disruption in aquatic vertebrates.
2009,
Pubmed
Krohmer,
Distribution of aromatase immunoreactivity in the forebrain of red-sided garter snakes at the beginning of the winter dormancy.
2002,
Pubmed
Kuntz,
Cerebral and gonadal aromatase expressions are differently affected during sex differentiation of Pleurodeles waltl.
2004,
Pubmed
Lam,
gfap and nestin reporter lines reveal characteristics of neural progenitors in the adult zebrafish brain.
2009,
Pubmed
Langlois,
Fadrozole and finasteride exposures modulate sex steroid- and thyroid hormone-related gene expression in Silurana (Xenopus) tropicalis early larval development.
2010,
Pubmed
,
Xenbase
Lee,
Conversion of Xenopus ectoderm into neurons by NeuroD, a basic helix-loop-helix protein.
1995,
Pubmed
,
Xenbase
Lephart,
A review of brain aromatase cytochrome P450.
1996,
Pubmed
Lin,
Regeneration of neural crest derivatives in the Xenopus tadpole tail.
2007,
Pubmed
,
Xenbase
MacLusky,
Sexual differentiation of the central nervous system.
1981,
Pubmed
Marsh,
Aromatase immunoreactivity in the bluehead wrasse brain, Thalassoma bifasciatum: immunolocalization and co-regionalization with arginine vasotocin and tyrosine hydroxylase.
2006,
Pubmed
Martínez-Cerdeño,
Estradiol stimulates progenitor cell division in the ventricular and subventricular zones of the embryonic neocortex.
2006,
Pubmed
März,
Heterogeneity in progenitor cell subtypes in the ventricular zone of the zebrafish adult telencephalon.
2010,
Pubmed
McCullough,
Aromatase cytochrome P450 and extragonadal estrogen play a role in ischemic neuroprotection.
2003,
Pubmed
Mensah-Nyagan,
Neurosteroids: expression of steroidogenic enzymes and regulation of steroid biosynthesis in the central nervous system.
1999,
Pubmed
Menuet,
Expression and estrogen-dependent regulation of the zebrafish brain aromatase gene.
2005,
Pubmed
Menuet,
Distribution of aromatase mRNA and protein in the brain and pituitary of female rainbow trout: Comparison with estrogen receptor alpha.
2003,
Pubmed
Metzdorf,
Distribution of aromatase, estrogen receptor, and androgen receptor mRNA in the forebrain of songbirds and nonsongbirds.
1999,
Pubmed
Mouriec,
Early regulation of brain aromatase (cyp19a1b) by estrogen receptors during zebrafish development.
2009,
Pubmed
Naftolin,
Brain aromatization of androgens.
1994,
Pubmed
Panzica,
The sexually dimorphic medial preoptic nucleus of quail: a key brain area mediating steroid action on male sexual behavior.
1996,
Pubmed
Pasmanik,
Aromatase and 5 alpha-reductase in the teleost brain, spinal cord, and pituitary gland.
1985,
Pubmed
Pellegrini,
Identification of aromatase-positive radial glial cells as progenitor cells in the ventricular layer of the forebrain in zebrafish.
2007,
Pubmed
Pérez,
Relationships between radial glial progenitors and 5-HT neurons in the paraventricular organ of adult zebrafish - potential effects of serotonin on adult neurogenesis.
2013,
Pubmed
Peterson,
Rapid upregulation of aromatase mRNA and protein following neural injury in the zebra finch (Taeniopygia guttata).
2001,
Pubmed
Peterson,
Radial glia express aromatase in the injured zebra finch brain.
2004,
Pubmed
Resko,
Prenatal hormones organize sex differences of the neuroendocrine reproductive system: observations on guinea pigs and nonhuman primates.
1997,
Pubmed
Roselli,
Brain aromatization: classic roles and new perspectives.
2009,
Pubmed
Roselli,
Distribution and regulation of aromatase activity in the rat hypothalamus and limbic system.
1985,
Pubmed
Roselli,
Brain aromatase: roles in reproduction and neuroprotection.
2007,
Pubmed
Rothenaigner,
Clonal analysis by distinct viral vectors identifies bona fide neural stem cells in the adult zebrafish telencephalon and characterizes their division properties and fate.
2011,
Pubmed
Saldanha,
Distribution and regulation of telencephalic aromatase expression in the zebra finch revealed with a specific antibody.
2000,
Pubmed
Schlinger,
The activity and expression of aromatase in songbirds.
1997,
Pubmed
Servili,
Organization of two independent kisspeptin systems derived from evolutionary-ancient kiss genes in the brain of zebrafish.
2011,
Pubmed
Simpson,
Aromatase--a brief overview.
2002,
Pubmed
Simpson,
Aromatase: biologic relevance of tissue-specific expression.
2004,
Pubmed
Strobl-Mazzulla,
Brain aromatase from pejerrey fish (Odontesthes bonariensis): cDNA cloning, tissue expression, and immunohistochemical localization.
2005,
Pubmed
Tanaka,
Considering the evolution of regeneration in the central nervous system.
2009,
Pubmed
Urbatzka,
Aromatase, steroid-5-alpha-reductase type 1 and type 2 mRNA expression in gonads and in brain of Xenopus laevis during ontogeny.
2007,
Pubmed
,
Xenbase
Villalpando,
Determination of the sensitive stages for gonadal sex-reversal in Xenopus laevis tadpoles.
1990,
Pubmed
,
Xenbase
Wagner,
Neuroanatomical distribution of aromatase MRNA in the rat brain: indications of regional regulation.
1997,
Pubmed
Wu,
Estrogen masculinizes neural pathways and sex-specific behaviors.
2009,
Pubmed
Yague,
Aromatase expression in the human temporal cortex.
2006,
Pubmed
Yague,
Aromatase distribution in the monkey temporal neocortex and hippocampus.
2008,
Pubmed
