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ABSTRACT: Androgen influences the function of central and peripheral nervous system and plays a crucial role in maintaining reproductive behaviors and neuroendocrine regulation. Such action is mediated by interaction of androgen receptor (AR) promoter with nuclear proteins, which are involved in transcriptional regulation of androgen responsive genes. We have analyzed the binding of AR core promoter to nuclear proteins from the cerebral cortex of adult and old mice of both sexes by electrophoretic mobility shift assay (EMSA) and characterized the bound protein by Southwestern blotting. EMSA showed that the binding of nuclear proteins declined in the cerebral cortex of intact old mice as compared to adult. Following gonadectomy, the binding was reduced in old male and adult female but increased in old female. In contrast, estradiol supplementation increased the binding in old male and adult female but decreased in old female. Southwestern blotting analysis revealed that a 40 kDa nuclear protein bound to the promoter and the binding pattern was similar to that observed in EMSA. Further characterization of this protein may help to explore the intricate mechanism that underlies the transcriptional regulation of androgen responsive genes during aging.
Biogerontology 11/2007; 8(5):575-82. · 3.34 Impact Factor
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ABSTRACT: We have previously reported that androgen receptor (AR) expression is inversely correlated to its promoter methylation and is regulated by sex steroids. As chromatin structure plays an important role in transcriptional regulation, the effect of sex steroids on DNaseI accessibility of chromatin of AR promoter was examined in the brain cortex of adult and old mice of both sexes. Nuclei were digested with different concentrations of DNaseI and the extracted DNA was further cleaved by PstI and analyzed by Southern hybridization with DIG-labeled 695-bp AR promoter. With 50 U DNaseI, the intensity of PstI-specific 1.45-kb band was lower in intact female as compared to male groups, suggesting increased nuclease accessibility in female than male. Although gonadectomy increased DNaseI accessibility remarkably in male and female of both ages, testosterone decreased the accessibility in adult but increased in old male. Estradiol, on the other hand, decreased DNaseI accessibility in both adult male and old female but increased in old male and adult female. Thus, these findings suggest that the chromatin conformation of AR promoter varies with age and sex and its accessibility to DNaseI is reduced by testosterone and estradiol in the brain cortex of adult male mice.
Molecular Brain Research 12/2004; 131(1-2):1-7. · 2.00 Impact Factor
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ABSTRACT: Androgen receptor (AR) is expressed in different tissues including the brain and is under regulation by sex steroid hormones. It mediates the action of androgen which plays a key role in learning, memory, and other brain functions that deteriorate with increasing age. We have correlated the expression of AR mRNA with its promoter methylation and their regulation by testosterone and estradiol in the brain cortex of adult and old male and female mice. Results revealed that (i) AR mRNA expression was significantly higher in male than in female mice. (ii) In both sexes, AR mRNA level was down-regulated by testosterone in adult and old, but up-regulated by estradiol only in adult mice. (iii) Methylation of AR core promoter was increased by testosterone, but decreased by estradiol. These findings show that AR mRNA expression and its core promoter methylation are inversely regulated by testosterone and estradiol in the adult mice brain cortex. Such regulation of AR expression might influence androgen action during aging of the mice brain.
Neurobiology of Aging 09/2004; 25(7):925-33. · 6.19 Impact Factor
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ABSTRACT: Norbin is a novel neuron specific protein that extends the neurites of neuronal cells. It is expressed in neural tissues like brain cortex, hippocampus, spinal cord and cerebellum. In this paper, we have studied the expression of norbin mRNA and protein in the brain cortex of male and female mice of different ages. Northern blot analysis showed that the level of norbin mRNA increased in both sexes during aging. However, Western blotting revealed that the protein increased in male but decreased in female with advancing age. These findings suggest that norbin is involved in brain function which is dependent on age and sex.
Neuroscience Letters 08/2001; 308(1):57-9. · 2.11 Impact Factor
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ABSTRACT: We have previously reported that androgen receptor (AR) expression is inversely correlated to its promoter methylation and is regulated by sex steroids. As chromatin structure plays an important role in transcriptional regulation, the effect of sex steroids on DNaseI accessibility of chromatin of AR promoter was examined in the brain cortex of adult and old mice of both sexes. Nuclei were digested with different concentrations of DNaseI and the extracted DNA was further cleaved by PstI and analyzed by Southern hybridization with DIG-labeled 695-bp AR promoter. With 50 U DNaseI, the intensity of PstI-specific 1.45-kb band was lower in intact female as compared to male groups, suggesting increased nuclease accessibility in female than male. Although gonadectomy increased DNaseI accessibility remarkably in male and female of both ages, testosterone decreased the accessibility in adult but increased in old male. Estradiol, on the other hand, decreased DNaseI accessibility in both adult male and old female but increased in old male and adult female. Thus, these findings suggest that the chromatin conformation of AR promoter varies with age and sex and its accessibility to DNaseI is reduced by testosterone and estradiol in the brain cortex of adult male mice.
Molecular Brain Research.
