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ABSTRACT: Estrogen-like endocrine disrupting chemicals (EEDC) are exogenous, man-made chemicals that alter the functions of the endocrine system and cause various health defects by interfering with the synthesis, metabolism, binding or cellular responses of natural estrogens. EEDCs have been found in various plastic products, flame retardants, pesticides and many other products that are needed for daily use. Some of the greatest effects of EEDCs are on puberty, a period of rapid physiological changes like growth spurt, maturation of the gonads and the brain. Estrogen, one of the key hormones required in puberty is crucial for the sexual differentiation. The structural similarity of estrogen disruptors with estrogen allow them to bind and activate estrogen receptors and show a similar response even in the absence of estrogen that can lead to precocious puberty (PP). Major EEDCs found abundantly in our environment include; dichlorodiphenyltrichloroethane (DDT), dioxin, polychlorinated biphenyls (PCBs), bisphenol A (BPA), polybrominated biphenyls (PBB), phthalate esters, endosulfan, atrazine and zeranol. In girls, DDT has been linked to earlier menarche. Dioxin causes abnormal breast development in pre-pubertal girls. BPA has shown to cause PP in pubertal girls. PBB causes earlier menarche, thelarche and earlier pubic hair stage in pubertal girls. PCB's showed a significant delay in puberty in pubertal boys. De-feminization, thelarche, or early secondary breast development are shown in pubertal girls when exposed to phthalate esters. Endosulfan affects pubertal boys by slowing down the timing of reproductive maturation. This article provides a possible structure-function relation of the above mentioned EEDCs which interfere with sexual development during puberty.
Medical science monitor: international medical journal of experimental and clinical research 07/2009; 15(6):RA137-45. · 1.70 Impact Factor
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ABSTRACT: Circulating gonadal steroid levels affect metabolic homeostasis by regulating appetite and food intake. The actions of estrogen are mediated through its two receptors ERalpha and ERbeta. ERalpha expression is necessary to maintain normal food intake, body weight and adiposity. Leptin plays a central role in regulating feeding behavior, homeostasis and reproduction. It is known that there is an effect of estrogen and leptin on feeding behavior. The present study was undertaken 1) to assess the changes in the reproductive cycle in obese, infertile ob/ob mice with no circulating leptin and infertile, obese, agouti (Ay/a) mice with high circulating leptin levels, 2) to evaluate the hypothalamic distribution of ERalpha and ERbeta, and 3) to analyze the differences in expression of ERs related to leptin and beta-estradiol levels in these mouse lines. The results show that the ob/ob and Ay/a mice were acyclic and were at a persistent estrous phase. The beta-estradiol levels were similar between WT, ob/ob and Ay/a mice. Stereologic analysis showed that there were significantly higher numbers of ERalpha-immunoreactive cells in ob/ob mice irrespective of sex when compared to wild-type (WT) in arcuate nucleus (ARH) and no significant change in ERbeta immunoreactive cell numbers in ARH or paraventricular nucleus (PVN). Ovariectomy in female wild-type mice caused a 50% increase of ERalpha-immunoreactive cells. Results suggest that leptin and estrogen act via the same neuronal circuits to affect reproduction, neuroendocrine and behavioral processes. However, estrogen levels and acyclicity have more profound effect on the regulation of ERalpha cell numbers in the ARH than circulating leptin levels.
Brain Research 07/2008; 1217:86-95. · 2.73 Impact Factor
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ABSTRACT: Sequence analysis using the Promoser program predicted two promoter-like regions for rat mtGPAT: a distal promoter approximately 30kb upstream and a proximal promoter near the first translational codon. Rat liver cells transfected with pGL3-basic vector containing the distal and proximal promoter resulted in 10.8- and 4.8-fold increase in the luciferase activity, respectively. Results of electromobility shift assay and chromatin immunoprecipitation suggested binding of transcription factors to the distal and proximal promoter regions. 5' RACE PCR showed two transcripts with different transcriptional start sites. When transfected rat liver cells were starved and refed, there was about 2.7-fold increase in the luciferase activity with cells transfected with the distal promoter while the proximal promoter showed no change. Thus, the two promoters could be functionally distinguished. Taken together, the results suggest that there are two promoters for rat mtGPAT gene and that the transcriptional regulation is mediated through the distal promoter.
Archives of Biochemistry and Biophysics 03/2008; 470(1):35-43. · 2.93 Impact Factor
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ABSTRACT: We have previously shown rat liver mitochondrial glycerol-3-phosphate acyltransferase (mtGAT), which catalyzes the first step in de novo glycerolipid biosynthesis, is stimulated by casein kinase 2 (CK2) and that a phosphorylated protein of approximately 85 kDa is present in CK2-treated mitochondria. In this paper, we have identified the (32)P-labeled 85-kDa protein as mtGAT. We have also investigated whether the phosphorylation of mtGAT is because of CK2. Mitochondria were treated with CK2 and [gamma-(32)P]GTP as the phosphate donor. Autoradiography, Western blot, and immunoprecipitation results showed mtGAT was phosphorylated by CK2. Next, we incubated mitochondria with CK2 and either ATP or GTP, in the presence of heparin, a known inhibitor of CK2. Heparin inhibited CK2-induced stimulation of mtGAT activity; this inhibition resulted in decreased (32)P-labeling of mtGAT. Additionally, mitochondria were treated with CK2 and [gamma-(32)P]ATP in the presence of staurosporine (a serine/threonine protein kinase inhibitor), genistein (a tyrosine kinase inhibitor), and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB, a CK2 inhibitor). Only DRB, the CK2 inhibitor, greatly reduced the amount of (32)P-incorporation into mtGAT by CK2. Finally, isolated mitochondrial outer membrane was incubated with cytosol in the presence of [gamma-(32)P]GTP; (32)P-labeled mtGAT was detected. Collectively, these data suggest that CK2 phosphorylates mtGAT. The impact of our results in the regulation of mtGAT and other anabolic processes is discussed.
Journal of Biological Chemistry 06/2005; 280(20):19527-34. · 4.77 Impact Factor
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ABSTRACT: The purpose of this investigation was to determine how polymyxin B stimulates the activity of mitochondrial glycerophosphate acyltransferase. Polymyxin B did not change the integrity of the mitochondrial outer membrane as judged by testing the latency (>80%) of cytochrome oxidase activity. The stimulation totally disappeared when polymyxin B-treated mitochondria were washed. The FA side chain in polymyxin B was unnecessary for stimulation, as the nonapeptide was as effective as the whole antibiotic. The stimulation by polymyxin B or the nonapeptide was observed only in the presence of BSA. Cytochrome c, when added to the incubation medium instead of albumin, did not stimulate the mitochondrial enzyme, but did produce a stimulatory effect of polymyxin B on the mitochondrial acyltransferase. As reported earlier for the bacterial and microsomal acyltransferase, other polycationic compounds such as spermine and spermidine stimulated mitochondrial glycerophosphate acyltransferase. The stimulation of the mitochondrial acyltransferase by spermine and spermidine also occurred only in the presence of BSA. The analysis of the products of esterification demonstrated the presence of more lysophosphatidic acid (LPA) in the polymyxin B- and polyamine-stimulated assays in comparison to their respective control. Furthermore, in comparison to the albumin-treated control, there was 60% more LPA present in the assay supernatant fractions of polymyxin B-treated samples. Our results suggest that polymyxin B stimulates the mitochondrial glycerophosphate acyltransferase activity by enhancing the extraction of more LPA from the mitochondria to the supernatant fraction.
Lipids 10/2003; 38(9):965-72. · 2.13 Impact Factor
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ABSTRACT: The purpose of this investigation was to determine how polymyxin B stimulates the activity of mitochondrial glycerophosphate
acyltransferase. Polymyxin B did not change the integrity of the mitochondrial outer membrane as judged by testing the latency
(>80%) of cytochrome oxidase activity. The stimulation totally disappeared when polymyxin B-treated mitochondria were washed.
The FA side chain in polymyxin B was unnecessary for stimulation, as the nonapeptide was as effective as the whole antibiotic.
The stimulation by polymyxin B or the nonapeptide was observed only in the presence of BSA. Cytochrome c, when added to the
incubation medium instead of albumin, did not stimulate the mitochondrial enzyme, but did produce a stimulatory effect of
polymyxin B on the mitochondrial acyltransferase. As reported earlier for the bacterial and microsomal acyltransferase, other
polycationic compounds such as spermine and spermidine stimulated mitochondrial glycerophosphate acyltransferase. The stimulation
of the mitochondrial acyltransferase by spermine and spermidine also occurred only in the presence of BSA. The analysis of
the products of esterification demonstrated the presence of more lysophosphatidic acid (LPA) in the polymyxin B-and polyamine-stimulated
assays in comparison to their respective control. Furthermore, in comparison to the albumin-treated control, there was 60%
more LPA present in the assay supernatant fractions of polymyxin B-treated samples. Our results suggest that polymyxin B stimulates
the mitochondrial glycerophosphate acyltransferase activity by enhancing the extraction of more LPA from the mitochondria
to the supernatant fraction.
Lipids 08/2003; 38(9):965-972. · 2.13 Impact Factor
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ABSTRACT: Circulating gonadal steroid levels affect metabolic homeostasis by regulating appetite and food intake. The actions of estrogen are mediated through its two receptors ERα and ERβ. ERα expression is necessary to maintain normal food intake, body weight and adiposity. Leptin plays a central role in regulating feeding behavior, homeostasis and reproduction. It is known that there is an effect of estrogen and leptin on feeding behavior. The present study was undertaken 1) to assess the changes in the reproductive cycle in obese, infertile ob/ob mice with no circulating leptin and infertile, obese, agouti (Ay/a) mice with high circulating leptin levels, 2) to evaluate the hypothalamic distribution of ERα and ERβ, and 3) to analyze the differences in expression of ERs related to leptin and β-estradiol levels in these mouse lines. The results show that the ob/ob and Ay/a mice were acyclic and were at a persistent estrous phase. The β-estradiol levels were similar between WT, ob/ob and Ay/a mice. Stereologic analysis showed that there were significantly higher numbers of ERα-immunoreactive cells in ob/ob mice irrespective of sex when compared to wild-type (WT) in arcuate nucleus (ARH) and no significant change in ERβ immunoreactive cell numbers in ARH or paraventricular nucleus (PVN). Ovariectomy in female wild-type mice caused a 50% increase of ERα-immunoreactive cells. Results suggest that leptin and estrogen act via the same neuronal circuits to affect reproduction, neuroendocrine and behavioral processes. However, estrogen levels and acyclicity have more profound effect on the regulation of ERα cell numbers in the ARH than circulating leptin levels.
Brain Research.
