scholarly journals Adrenal Corticosteroid Perturbation by the Endocrine Disruptor BDE-47 in a Human Adrenocortical Cell Line and Male Rats

Endocrinology ◽  
2021 ◽  
Author(s):  
Benjamin M Dungar ◽  
Chad D Schupbach ◽  
Jessie R Jacobson ◽  
Phillip G Kopf
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Polybrominated Diphenyl Ethers ◽  
Plasma Corticosterone ◽  
Male Rats ◽  
Cortisol Secretion ◽  
Adrenocortical Cell ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Corticosteroid Secretion

Abstract Polybrominated diphenyl ethers (PBDEs) have been previously shown to alter various endocrine biosynthetic pathways. Growing epidemiological evidence suggests that PBDEs alter cardiovascular function. The goal of this study was to examine the effects of BDE-47 on adrenal corticosteroid pathways that play vital roles in cardiovascular homeostasis and pathophysiology. The effect of BDE-47 on aldosterone and cortisol secretion was characterized in a human adrenocortical cell line. HAC15 cells were exposed to various concentrations of BDE-47 (1 nM-100 μM). Cell viability, corticosteroid secretion, gene expression of enzymes involved in corticosteroid synthesis, and metabolic activity was examined. Additionally, Sprague Dawley male rats were orally exposed to BDE-47 (10 or 100 µg/kg), 5 days per week for 16 weeks. Organ weights and plasma corticosteroid levels were measured. In HAC15 cells, basal and stimulated aldosterone and cortisol secretion was significantly increased by BDE-47. Gene expression of several enzymes involved in corticosteroid synthesis and mitochondrial metabolism were also increased. In Sprague Dawley rats, adrenal, but not heart, kidney, or liver weights, were significantly increased in BDE-47 treatment groups. Plasma corticosterone levels were significantly increased in the 100 µg BDE-47/kg treatment group. No change in plasma aldosterone levels were observed with BDE-47 exposure. These data indicate that BDE-47 disrupts the regulation of corticosteroid secretion and provides further evidence that PBDEs are potential endocrine disruptors. Future studies will determine the underlying molecular mechanism of altered corticosteroid production and examine whether these alterations result in underlying cardiovascular disease in our rodent model of 16 week BDE-47 exposure.

scholarly journals Effects of repeated doses and continuous infusions of the growth hormone-releasing peptide hexarelin in conscious male rats

1998 ◽  
Vol 158 (3) ◽  
pp. 367-375 ◽  
Author(s):  
LK Conley ◽  
RC Gaillard ◽  
A Giustina ◽  
RS Brogan ◽  
WB Wehrenberg
Keyword(s):  
Adult Male ◽  
Plasma Corticosterone ◽  
Male Rats ◽  
Continuous Exposure ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Sprague Dawley Rats ◽  
Repeated Doses ◽  
The Mean ◽  
Plasma Gh

We have previously shown that hexarelin, a novel GH-releasing peptide (GHRP), is able to elicit GH release when administered i.v., s.c. or by mouth and that it is a more potent GH secretagogue than GHRP-6. In the current study, we investigated the effects of hexarelin administered as repeated doses at 2 h intervals or as a continuous 6, 30 or 174 h infusion to conscious male rats. In the first experiment, adult male Sprague-Dawley rats were prepared with dual indwelling jugular catheters. On the day of experimentation, these animals received three 25 micrograms/kg i.v. boluses of hexarelin at 2 h intervals with blood sampling at 5, 10, 15, 30, 60, 90 and 120 min after each dose. The mean peak GH response and the mean area under the GH response curve (AUC) for the 30 min after each administration were calculated and are reported as the mean +/- S.E.M. For both the peak and AUC results there was a significant (P < 0.05) difference in the GH response noted between the first (peak 301 +/- 37 ng/ml; AUC 5585 +/- 700 ng/ml per 30 min) and second (peak 149 +/- 47 ng/ml; AUC 3056 +/- 908 ng/ml per 30 min) injections of hexarelin, but not between the first and third (peak 214 +/- 49 ng/ml; AUC 3862 +/- 844 ng/ml per 30 min). In a second series of experiments, adult male Sprague-Dawley rats received continuous infusions (100 micrograms/h) of hexarelin or saline (1 ml/h) for 6, 30 or 174 h. Blood samples were collected every 20 min for the duration of the 6 h infusion and for the last 6 h of the two longer hexarelin infusions. Plasma GH concentrations peaked within 40 min of the initiation of infusion, but soon returned to basal levels. Mean plasma GH concentrations did not differ between any of the treatment groups, nor did any of the parameters of pulsatile hormone release analyzed. No significant differences in plasma corticosterone concentrations were noted between any of the treatment groups. On the other hand, while neither the 6 h (941 +/- 70 ng/ml) nor the 30 h (954 +/- 70 ng/ml) hexarelin infusions resulted in a significant increase in the plasma IGF-I concentrations over those noted in the saline controls (935 +/- 65 ng/ml), a 174 h hexarelin infusion did elicit a significant increase (1289 +/- 42 ng/ml; P < 0.05). Thus it appears that, while continuous exposure to hexarelin does not disrupt normal GH cycling, it may (after up to 174 h of exposure) alter other components of the growth axis. In addition, since the character of pulsatile GH release remained unaltered in response to the hexarelin infusion, it appears that this GHRP may not act by suppression of functional somatostatin tone as has been suggested previously.

Regulation of ACTH-R gene expression by CREB, CREMt and ICER in the adrenocortical cell line Y1

2005 ◽  
Vol 113 (S 1) ◽  
Author(s):  
O Zwermann ◽  
A Braun ◽  
E Lalli ◽  
F Beuschlein ◽  
M Reincke
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
R Gene ◽  
Adrenocortical Cell

Regulation of Human MC2-R Gene Expression by CREB, CREM, and ICER in the Adrenocortical Cell Line Y1

2007 ◽  
Vol 39 (8) ◽  
pp. 560-566 ◽  
Author(s):  
O. Zwermann ◽  
A. Braun ◽  
E. Lalli ◽  
P. Sassone-Corsi ◽  
F. Beuschlein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
R Gene ◽  
Adrenocortical Cell

scholarly journals In Utero and Lactational Exposure to Flame Retardants Disrupts Rat Ovarian Follicular Development and Advances Puberty

2020 ◽  
Vol 175 (2) ◽  
pp. 197-209 ◽  
Author(s):  
Adélaïde Allais ◽  
Océane Albert ◽  
Pavine L C Lefèvre ◽  
Michael G Wade ◽  
Barbara F Hales ◽  
...  
Keyword(s):  
Gene Expression ◽  
Polybrominated Diphenyl Ethers ◽  
Flame Retardants ◽  
Ovarian Function ◽  
Expression Patterns ◽  
Follicular Development ◽  
In Utero ◽  
Consumer Products ◽  
Sprague Dawley ◽  
Lactational Exposure

Abstract Brominated flame retardants (BFRs), including polybrominated diphenyl ethers and hexabromocyclododecane, leach out from consumer products into the environment. Exposure to BFRs has been associated with effects on endocrine homeostasis. To test the hypothesis that in utero and lactational exposure to BFRs may affect the reproductive system of female offspring, adult female Sprague Dawley rats were fed diets formulated to deliver nominal doses (0, 0.06, 20, or 60 mg/kg/day) of a BFR dietary mixture mimicking the relative congener levels in house dust from prior to mating until weaning. Vaginal opening and the day of first estrus occurred at a significantly earlier age among offspring from the 20 mg/kg/day BFR group, indicating that the onset of puberty was advanced. Histological analysis of ovaries from postnatal day 46 offspring revealed an increase in the incidence of abnormal follicles. A toxicogenomic analysis of ovarian gene expression identified upstream regulators, including HIF1A, CREB1, EGF, the β-estradiol, and PPARA pathways, predicted to be downregulated in the 20 or 60 mg/kg/day group and to contribute to the gene expression patterns observed. Thus, perinatal exposure to BFRs dysregulated ovarian folliculogenesis and signaling pathways that are fundamental for ovarian function in the adult.

STUDIES ON THE BIOSYNTHESIS OF TESTOSTERONE IN THE RAT

1971 ◽  
Vol 68 (3) ◽  
pp. 614-624 ◽  
Author(s):  
Z. Kniewald ◽  
M. Zanisi ◽  
L. Martini
Keyword(s):  
Adrenal Gland ◽  
Sharp Decrease ◽  
Plasma Corticosterone ◽  
Male Rats ◽  
Plasma Testosterone ◽  
Normal Male ◽  
Sprague Dawley ◽  
Unilateral Adrenalectomy ◽  
Sprague Dawley Rats ◽  
Chromatographic Procedure

ABSTRACT Plasma levels of testosterone have been measured in adult male Sprague-Dawley rats using a gas-chromatographic procedure. Immediately after castration, the concentrations of testosterone in the plasma increase to reach a maximum one hour after orchidectomy; after this time a progressive decrease in plasma testosterone is observed. The concentration of testosterone then returns to levels close to those found before the operation two hours after castration; four hours after orchidectomy plasma testosterone begins to decrease to values lower than in the intact controls. Adrenalectomized animals with their testes in situ show a sharp decrease in plasma testosterone which begins immediately after the operation; the plasma testosterone reaches levels significantly lower than those in the intact control one hour after adrenalectomy; a greater decrease is observed four hours after the operation. Twenty-four hours after unilateral adrenalectomy the remaining gland significantly increases in weight; at this time, the plasma corticosterone and plasma testosterone levels of unilaterally adrenalectomized rats are normal. These results are interpreted as indicating that the adrenal gland of normal male rats is capable of producing testosterone, and that the synthesis of testosterone at the adrenal level is increased immediately after castration. Moreover it is suggested that the adrenal gland also contributes to the biosynthesis of testosterone in an indirect fashion, i. e. by providing the testes with an essential precursor. It has been tentatively proposed that progesterone might be such a precursor.

scholarly journals Intestinal sepsis model of small animals

2020 ◽  
Vol 7 (3) ◽  
pp. 44-46
Author(s):  
Ramesh Reddy ◽  
Suman Rao
Keyword(s):  
Peritoneal Fluid ◽  
Male Rats ◽  
Histopathological Study ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
E Coli ◽  
Sepsis Model ◽  
Liver Surface ◽  
Intraperitoneal Infection ◽  
Fluid Culture

Objective: The goal of this paper was to develop a model of intestinal sepsis in the investigational animal. Material and methods. Sprague-Dawley male rats of 4 weeks (N = 42) were used. Initially, a pilot study (N = 12) was performed and distributed in groups with .8 cc inoculum of Escherichia coli ATCC intraperitoneally administered at concentrations of 9, 7, 6. Subsequently, concentrations of 9 CFU are used in two groups of rats with reductions of 11 cc.  Finally, a randomized trial of 28 rats was initiated in three treatment groups after intraperitoneal infection. Biological models of blood and peritoneal fluid were observed, and histopathological study of intraperitoneal tissues was done. Results. Demise of 95% of the rats infected with E. coli UFC concentration was observed. The blood culture and peritoneal fluid culture was positive for the same strain in all of them. The formation of blisters on the liver surface and polymorphonuclear infiltration in organs were detected. Conclusion. The fatal dose of E. coli should be diluted for intraperitoneal injection.

Castration attenuates prolactin response but potentiates ACTH response to conditioned stress in the rat

1995 ◽  
Vol 269 (4) ◽  
pp. R856-R863 ◽  
Author(s):  
E. W. Bingaman ◽  
L. D. Van de Kar ◽  
J. M. Yracheta ◽  
Q. Li ◽  
T. S. Gray
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Behavioral Responses ◽  
Plasma Renin ◽  
Plasma Corticosterone ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Sprague Dawley Rats ◽  
Response To Stress ◽  
Prolactin Response ◽  
Psychological Stressor

The purpose of this study was to examine the effect of circulating androgens on neuroendocrine, autonomic, and behavioral responses to stress. The effects of conditioned stress were studied in male Sprague-Dawley rats that were intact, gonadectomized, or gonadectomized and treated with dihydrotestosterone (DHT). Intact animals received sham surgeries. Animals were stressed 3 wk after surgery. The adrenocorticotropic hormone (ACTH) response to conditioned stress was significantly potentiated (P < 0.01) in gonadectomized males compared with sham-operated and gonadectomized DHT-treated animals. In stressed rats, plasma corticosterone levels were significantly higher (P < 0.05) in gonadectomized animals compared with DHT-treated castrates. The prolactin response to stress was decreased (P < 0.01) in gonadectomized males compared with sham-operated and gonadectomized DHT-treated rats. The stress-induced increases in plasma renin activity and concentration were not altered in gonadectomized or in gonadectomized DHT-treated animals. Nonstressed DHT-treated castrates exhibited more “fearlike” behavior compared with nonstressed sham-operated and gonadectomized animals. However, conditioned stress produced the same behavioral effects in all treatment groups. The results demonstrate that the ACTH/corticosterone, prolactin, and behavioral responses to a psychological stressor are differentially regulated by circulating androgens.

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