Expression and localization of aromatase P450AROM, estrogen receptor-α, and estrogen receptor-β in the developing fetal bovine frontal cortex
ABSTRACT The enzyme aromatase (P450(AROM)) converts testosterone (T) into 17-β estradiol (E(2)) and is crucial for the control of development of the central nervous system during ontogenesis. The effects of E(2) in various brain areas are mediated by the estrogen receptor alpha (ER-α) and the estrogen receptor beta (ER-β). During fetal development, steroids are responsible for the sexual differentiation of the hypothalamus. Estrogens are also able to exert effects in other brain areas of the fetus including the frontal cortex, where they act through estrogen receptors (ERs) modulating cognitive function and affective behaviors. In this study we have determined the expression profiles of P450(AROM) and ERs in the fetal bovine frontal cortex by quantitative Real-Time PCR (qRT-PCR) throughout the prenatal development. The data show that the patterns of expression of both ERs are strongly correlated during pregnancy and increase in the last stage of gestation. On the contrary, the expression of P450(AROM) has no correlation with ERs expression and is not developmentally regulated. Moreover, we performed immunochemical studies showing that fetal neurons express P450(AROM) and the ERs. P450(AROM) is localized in the cytoplasm and only seldom present in the fine extensions of the cells; ER-α is detected predominantly in the soma whereas ER-β is only present in the nucleus of a few cells. This study provides new data on the development of the frontal cortex in a long gestation mammal with a large convoluted brain.
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- "During the last decade, our laboratory used this species to study the role of sexual steroids in the regulation of brain differentiation and the expression of cytochrome P450 aromatase, the key enzyme of estrogen biosynthesis (12), in relation to specific estrogen receptor subtypes (ERs). We quantified the expression profiles and neural localization of aromatase P450 and estrogen receptors α and β during consecutive developmental stages in fetal bovine hypothalamus and cerebral cortex (13, 14). Quantitative data analysis on expression patterns of both ERs in different bovine fetal brain regions indicates a strong reciprocal correlation during pregnancy and an increase in the last stage of gestation (14). "
ABSTRACT: Animal models provide convenient and clinically relevant tools in the research on neurodegenerative diseases. Studies on developmental disorders extensively rely on the use of laboratory rodents. The present mini-review proposes an alternative translational model based on the use of fetal bovine brain tissue. The bovine (Bos taurus) possesses a large and highly gyrencephalic brain and the long gestation period (41 weeks) is comparable to human pregnancy (38-40 weeks). Primary cultures obtained from fetal bovine brain constitute a validated in vitro model that allows examinations of neurons and/or glial cells under controlled and reproducible conditions. Physiological processes can be also studied on cultured bovine neural cells incubated with specific substrates or by electrically coupled electrolyte-oxide-semiconductor capacitors that permit direct recording from neuronal cells. Bovine neural cells and specific in vitro cell culture could be an alternative in comparative neuroscience and in neurodegenerative research, useful for studying development of normal and altered circuitry in a long gestation mammalian species. Use of bovine tissues would promote a substantial reduction in the use of laboratory animals.Frontiers in Pediatrics 07/2014; 2:74. DOI:10.3389/fped.2014.00074
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ABSTRACT: Neurobiological mechanisms involved in sexual differentiation of the central nervous system will be presented with a comparative view across vertebrates. Women and men differ in a wide variety of behavioral traits and in the probabilities of developing certain mental disorders. A brief overview of sex-chromosome pathways underlying sexual dimorphisms will be provided. We will describe most common brain phenotypes derived in vivo with magnetic resonance imaging, discuss the challenges in interpreting these phenotypes vis-à-vis the underlying neurobiology and revise the known sex differences in brain structure from birth, through adolescence, to adulthood. Clinical and epidemiological data indicate important sex differences in the prevalence, course, and expression of psychopathologies such as schizophrenia, and mood disorders including major depression and bipolar illness. Recent evidence implies that mood disorders and psychosis share some common genetic predispositions, as well as some neurobiological basis. Therefore, modern research is emphasizing dimensional representation of mental disorders and conceptualization of schizophrenia, bipolar disorder and major depression as a continuum of cognitive deficits and neurobiological abnormalities. Herein, we have examined available evidence on cerebral sexual dimorphism in all three conditions to verify if sex differences vary quantitatively and/or qualitatively along the psychoses-depression continuum. Sex differences in posttraumatic disorders prevalence have also been described, thus data on differences at genomic and molecular levels will be considered. Finally, we will discuss the important contribution - advantages and limitations - of animal models in the investigation of underlying mechanisms of neurobehavioral sex differences in neuropsychiatric disorders, including drug dependence, with special emphasis in experimental models based on the neurodevelopmental and “three hits” hypotheses.Frontiers in Neuroscience 06/2012; 6:84. DOI:10.3389/fnins.2012.00084 · 3.70 Impact Factor
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ABSTRACT: With combined immunoperoxidase and immu-nofluorescence, we observed colocalization of cytochrome P450 aromatase with the posterior lobe peptide oxytocin and its associated neurophysin 1 in adult male rats. P450 was most abundant in the anterior hypothalamus. Colocalization of OT with P450 was observed in the preoptic region, the periventricular nucleus of the hypothalamus, the lateral subcommissural nucleus, and in the zona incerta. Magnocellular perikarya in the supraoptic and in the paraventricular nuclei contained only occasionally both antigens. P450 immunostaining overlapped to a great extent with known estrogen target regions. Oxytocinergic functions are controlled by estradiol while androgen receptors are mostly absent in neuroendocrine hypothalamic nuclei. Our findings suggest that systemic androgens may be aromatized to estrogens in male oxytocinergic neurons linked to the limbic system.Hormone and Metabolic Research 12/2012; 45(4). DOI:10.1055/s-0032-1327680 · 2.04 Impact Factor