Production Of Corticosterone In Rats Research Articles

Subchronic Noise and Metabolism: Rodent Model Identifies Potential Mechanistic Links.

Vol. 128, No. 3 Science SelectionOpen AccessSubchronic Noise and Metabolism: Rodent Model Identifies Potential Mechanistic Linksis accompanied byImpacts of Subchronic, High-Level Noise Exposure on Sleep and Metabolic Parameters: A Juvenile Rodent Model Silke Schmidt Silke Schmidt Search for more papers by this author Published:13 March 2020CID: 034004https://doi.org/10.1289/EHP6304View Article in:中文版AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail AbstractMultiple epidemiologic studies1,2,3 have linked chronic exposure to environmental noise with an increased risk of metabolic disorders, including obesity and diabetes. An experimental study published recently in Environmental Health Perspectives found consistent results in rodents, with gene expression and tissue analyses suggesting potential underlying mechanisms.4Epidemiological evidence has associated chronic noise exposure with metabolic changes, potentially stemming from sleep disturbances. A rat study of noise exposures during regular sleeping hours sought to tease out a mechanism that might explain these observations. Image: © iStockphoto/unoL.Researchers at Université de Picardie Jules Verne in Amiens, France, exposed 12 male Wistar rats to subchronic noise, meaning intermittent noisy periods of relatively long duration. For 37 days, starting at 3 weeks of age, the rats were exposed during their 12-hour sleep period to different sounds at levels comparable to the threshold commonly used in human studies of urban traffic noise. The noise exposure was followed by a noise-free 12-hour active period. Another 12 rats made up the control group.In the two groups of rats, the researchers compared physiologic parameters, sleep patterns, sleep apnea symptoms, post-sacrifice organ weights, and tissue mRNA expression levels of genes that regulate food intake and appetite. The noise-exposed rats consumed more food and water and gained 6% more body weight than the control animals. They also had heavier thymus and adrenal glands. Forebrain (hypothalamus) mRNA expression levels were higher for one gene (the cocaine- and amphetamine-regulated transcript gene, or CART) and lower for another (leptin receptor). Differences in sleep parameters between exposed and nonexposed animals, such as the duration of REM and non-REM sleep, were subtle, and there was no evidence of an effect on apnea during sleep.“Our study’s main finding is that noise exposure during the rest period increased food and water consumption, resulting in body and organ weight gain,” says senior author Amandine Pelletier, a lecturer in physiology. “Similar effects have been observed in human studies.”1,2,3An association between chronic noise exposure and greater thymus weight was previously reported in female adult rats.5 That finding suggested that noise-induced stress may influence metabolic function.6 Another study found that noise exposure increased the adrenal gland production of corticosterone in rats,7 which may lead to hypertrophy of the organ.8 Measuring blood levels of corticosterone and other hormones under a similar exposure protocol would be an interesting next step, says Pelletier.The noise-associated changes in mRNA expression levels may partially explain the observed body weight gain. Leptin is a hormone that inhibits hunger.9,10 The CART gene codes for neuropeptides involved in stress and reward pathways, whose expression is partially regulated by leptin.11 It is plausible that the leptin receptor and CART mRNAs may jointly influence circulating levels of leptin and other hormones, contributing to an increased appetite.Jennifer Teske, an associate professor of nutritional sciences at the University of Arizona in Tucson, who was not involved in the project, notes that an earlier study of rodents12 reported similar associations between noise exposure and weight gain. Recent work in Teske’s lab using female rats also found similar results.13 The current study’s gene expression analysis adds to the body of evidence by suggesting potential underlying mechanisms, she says.Zorana Jovanovic Andersen, a professor of environmental epidemiology at the University of Copenhagen, notes that, given the rat’s life span, the 36-day exposure period mimics long-term exposures that are relevant for human chronic disease development. For Andersen, who also was not involved in the study, the rodent findings are consistent with associations between chronic noise, sleep disturbances, and human diabetes. “The researchers also identified interesting and plausible explanations for these associations,” she says, “pointing at noise-related increased appetite and weight gain as the most relevant pathway.”Silke Schmidt, PhD, writes about science, health, and the environment from Madison, Wisconsin.

Inhibitory effects of bromocriptine on corticosterone secretion in male rats

Bromocriptine, a dopamine D2 receptor agonist, is widely used for treating prolactinoma, Parkinson's disease and galactorrhea. However, the influence of bromocriptine on the endocrine system, especially adrenal function, is not clear. The present study was aimed to investigate the effects of bromocriptine on corticosterone production in rats. Male rats were treated or not treated by bromocriptine (5 mg/kg, s.c.) twice per day for 2 days before decapitation. The adrenal zona fasciculata–reticularis cells were prepared and incubated with adrenocorticotropic hormone (ACTH), forskolin (an adenylyl cyclase activator), 8-bromo-adenosine 3′:5′ cyclic monophosphate (8-Br-cAMP, a membrane-permeable analogue of cAMP), and steroidogenic precursors including 25-OH-cholesterol and pregnenolone. The concentrations of prolactin, corticosterone and pregnenolone in the plasma and/or medium were measured by radioimmunoassay (RIA). The protein expression of cytochrome P450 side-chain cleavage (P450scc) enzyme and steroidogenic acute regulatory protein (StAR) was analyzed by Western blotting. Administration of bromocriptine in vivo resulted in a decrease in the levels of plasma prolactin and corticosterone. Basal—and ACTH—as well as forskolin-stimulated corticosterone secretion by zona fasciculata–reticularis cells was also lower in bromocriptine-treated rats than in control animals. The decreased production of corticosterone in zona fasciculata–reticularis cells could be reversed by administration of 8-Br-cAMP. The corticosterone and pregnenolone release induced by 25-OH-cholesterol in zona fasciculata–reticularis cells was reduced by administration of bromocriptine. The protein expression of both StAR protein and P450scc in zona fasciculata–reticularis cells was inhibited in the bromocriptine-treated group. Administration of bromocriptine in vitro reduced the release of corticosterone stimulated by ACTH and forskolin in rat zona fasciculata–reticularis cells. These results suggested that bromocriptine caused adrenal dysfunction through inhibition of ACTH action and of the activity of adenylyl cyclase, and impaired the early steps of corticosterone biosynthesis.

Effects of early experience on the metabolism and production of corticosterone in rats

Rats were handled for 3 min daily for 3 weeks before or after weaning or were left totally undisturbed. At 80 days of age, animals from each group were selected for corticosterone half-life determination. Adrenal tissue from thr remaining animals was incubated in vitro in the presence or absence of ACTH. Handled and unmanipulated animals did nto differ in half-life or in adrenocortical output. These data do not support the hypothesis that the reduced adrenocortical reactivity that results from manipulating animals is due to either the metabolsim of corticosterone or the response of the adrenal cortex to ACTH.

Effect of rubidium on aldosterone and corticosterone production in rats.

Rubidium was added to the food of male rats for 2 weeks and the aldosterone and corticosterone production of the adrenal glands was subsequently determined in vitro. The aldosterone production of Rb-treated rats was significantly higher than that of control animalsbut corticosterone production was not significantly altered. These findings indicate that the effects of Rb and K on the stimulation of aldosterone production in rats are similar. (Endocrinology81: 913,1967)