Estradiol receptors mediate estradiol-induced inhibition of mitochondrial Ca2+ efflux in rat caudate nucleus and brain stem

Our earlier studies found that in vitro estradiol modulates mitochondrial Ca2+ transport in discrete brain regions. The present study examined the role of estradiol receptors (ERs) in estradiol-induced inhibition of Ca2+ efflux from synaptosomal mitochondria isolated from rat caudate nuclei and brain stems. Radioactively labeled CaCl2 (0.6-0.75 mu Ci (CaCl2)-Ca-45) was used for Ca2+ transport monitoring. The results revealed that in the presence of ER antagonist 7 alpha, 17 beta-[9[(4,4,5,5,5-pentafluoropentyl) sulfinyl] nonyl] estra-1,3,5( 10)-triene-3,17-diol (ICI 182,780) (1 mu mol/L), the inhibitory effect of estradiol on mitochondrial Ca2+ efflux was more than 60% decreased, suggesting the involvement of ER in this mode of estradiol neuromodulatory action. When particular contributions of ER alpha and ER beta were tested, it was found that ER beta agonist 2,3-bis(4-hydroxy phenyl)-propionitrile (10 nmol/L) inhibited Ca2+ efflux more than 20%, while the inhibition with ER alpha agonist 4,4', 4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (10 nmol/L) was about 10%, both compared to the control. Both agonists demonstrated attenuation of Ca2+ efflux decrease in the presence of mitochondrial Na+/Ca2+ exchanger antagonist 7-chloro-5-(2-chlorophenyl)-1,5-dihyhdro-4,1-benzothiazepin-2(3H)-one (10 mu mol/L), showing interference with the inhibitory action of that agent. Our results strongly indicate ERs as the mediators of estradiol-induced mitochondrial Ca2+ efflux inhibition in rat caudate nucleus and brain stem synaptosomes

Involvement of glucocorticoid prereceptor metabolism and signaling in rat visceral adipose tissue lipid metabolism after chronic stress combined with high-fructose diet

Both fructose overconsumption and increased glucocorticoids secondary to chronic stress may contribute to overall dyslipidemia. In this study we specifically assessed the effects and interactions of dietary fructose and chronic stress on lipid metabolism in the visceral adipose tissue (VAT) of male Wistar rats. We analyzed the effects of 9-week 20% high fructose diet and 4-week chronic unpredictable stress, separately and in combination, on VAT histology, glucocorticoid prereceptor metabolism, glucocorticoid receptor subcellular redistribution and expression of major metabolic genes. Blood triglycerides and fatty acid composition were also measured to assess hepatic Delta 9 desaturase activity. The results showed that fructose diet increased blood triglycerides and Delta 9 desaturase activity. On the other hand, stress led to corticosterone elevation, glucocorticoid receptor activation and decrease in adipocyte size, while phosphoenolpyruvate carboxykinase, adipose tissue triglyceride lipase, FAT/CD36 and sterol regulatory element binding protein-1c (SREBP-1c) were increased, pointing to VAT lipolysis and glyceroneogenesis. The combination of stress and fructose diet was associated with marked stimulation of fatty acid synthase and acetylCoA carboxylase mRNA level and with increased 11 beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase protein levels, suggesting a coordinated increase in hexose monophosphate shunt and de novo lipogenesis. It however did not influence the level of peroxisome proliferator-activated receptor-gamma, SREBP-1c and carbohydrate responsive element-binding protein. In conclusion, our results showed that only combination of dietary fructose and stress increase glucocorticoid prereceptor metabolism and stimulates lipogenic enzyme expression suggesting that interaction between stress and fructose may be instrumental in promoting VAT expansion and dysfunction