scholarly journals Neonatal Gonadectomy and Adult Testosterone Replacement Suggest an Involvement of Limbic Arginine Vasopressin and Androgen Receptors in the Organization of the Hypothalamic-Pituitary-Adrenal Axis

Endocrinology ◽  
2008 ◽  
Vol 149 (7) ◽  
pp. 3581-3591 ◽  
Author(s):  
Brenda Bingham ◽  
Victor Viau
Keyword(s):  
Androgen Receptor ◽  
Hpa Axis ◽  
Paraventricular Nucleus ◽  
Arginine Vasopressin ◽  
Androgen Receptors ◽  
Male Rats ◽  
Testosterone Replacement ◽  
Testosterone Treatment ◽  
Hypothalamic Pituitary Adrenal ◽  
Hpa Response

Testosterone exposure during critical periods of development exerts major organizing effects on the hypothalamic-pituitary-adrenal (HPA) axis. Here we examined how neonatal gonadectomy (GDX) with or without testosterone treatment during the first week of life alters the HPA response to adult testosterone replacement in 65-d-old male rats. As adults, neonatal GDX rats showed higher levels of plasma corticosterone and Fos activation in medial parvocellular part of the paraventricular nucleus of the hypothalamus under basal conditions and during 30 min of restraint exposure. These responses were normalized with testosterone treatment on postnatal d 1–5 but were not restored with adult testosterone replacement. As adults, neonatal GDX rats also showed a decrease in the number of androgen receptor and arginine vasopressin-positive cells in the bed nucleus of the stria terminalis and in the medial nucleus of the amygdala, and both of these responses were reversed with postnatal testosterone treatment. In stressed and unstressed animals, the number of androgen receptors and arginine vasopressin-expressing neurons in both of these nuclei correlated negatively with corticosterone concentrations in plasma and Fos levels in the paraventricular nucleus. Taken together, our findings suggest that testosterone exposure during the neonatal period primes the adult HPA response to testosterone by altering androgen receptor levels and function within afferent mediators of basal and stress-related input to the HPA axis.

Consistent Reduction of ACTH responses to stimulation with CRH, Vasopressin and Hypoglycaemia in Patients with Major Depression

1989 ◽  
Vol 155 (4) ◽  
pp. 468-478 ◽  
Author(s):  
Roger G. Kathol ◽  
Richard S. Jaeckle ◽  
Juan F. Lopez ◽  
William H. Meller
Keyword(s):  
Major Depression ◽  
Hpa Axis ◽  
Negative Correlation ◽  
Arginine Vasopressin ◽  
Corticotropin Releasing Hormone ◽  
Hypothalamic Pituitary Adrenal ◽  
Releasing Hormone ◽  
Control Subjects ◽  
Basal Cortisol ◽  
Cortisol Responses

Eleven patients with major depression and 12 control subjects were administered corticotropin-releasing hormone (CRH), aqueous arginine vasopressin (AVP), and insulin hypoglycaemia (IH) to test for differences in hypothalamic–pituitary–adrenal (HPA) axis function. Patients with major depression demonstrated lower ACTH responses to CRH when compared with controls, and a trend toward such after administration of AVP. Despite lower ACTH responses in patients with depression, there were no differences in Cortisol responses to these stimuli. In the CRH and AVP tests, there was no correlation between the basal Cortisol and ACTH responses in either controls or patients, but in the IH test there was a negative correlation between these responses for both groups. The ACTH responses to CRH and AVP were positively correlated in controls and patients. Cortisol responses to all three provocative stimuli were positively correlated in both subject groups. These findings are consistent with the hypothesis that hypothalamic or supra-hypothalamic overactivity may be involved in the development of HPA-axis abnormalities in patients with depression.

scholarly journals Hypothalamic-pituitary-adrenal axis up-regulation in rats submitted to pituitary stalk compression

2004 ◽  
Vol 180 (2) ◽  
pp. 297-302 ◽  
Author(s):  
PC Elias ◽  
LL Elias ◽  
M Castro ◽  
J Antunes-Rodrigues ◽  
AC Moreira
Keyword(s):  
Hpa Axis ◽  
Water Intake ◽  
Immobilization Stress ◽  
Male Rats ◽  
Pituitary Stalk ◽  
Salt Loading ◽  
Hypothalamic Pituitary Adrenal ◽  
Salt Load ◽  
Post Surgery

The present study investigated the hypothalamic-pituitary-adrenal (HPA) axis activity in response to stress in adult male rats submitted to pituitary stalk compression (PSC) or sham operation. Animals received water or oral salt loading (2% NaCl) for one or eight days before the day of the experiment. On the 14th day post-surgery rats were killed under basal conditions or after 15 min immobilization stress. In the PSC group urine output increased significantly and plasma vasopressin (AVP) levels failed to respond to osmotic stimuli. Short-term salt load induced a significant increase in AVP levels in the sham-operated group. The PSC group presented higher adrenocorticotrophin (ACTH) and corticosterone levels compared with sham-operated rats, both in water intake and salt load conditions. Immobilization stress induced a similar increase in plasma ACTH and corticosterone concentrations in sham-operated and PSC groups under water intake. However, long-term salt load blunted the ACTH and corticosterone responses to immobilization stress in sham-operated rats. PSC rats submitted to short- and long-term salt loading presented no changes in ACTH and corticosterone levels after immobilization. Immobilization stress caused neither AVP responses nor plasma osmolality changes in sham and PSC groups. There was no difference in median eminence AVP content among all groups. In conclusion, the high ACTH and corticosterone levels found in PSC rats under water intake and salt loading conditions suggest an up-regulation of the HPA axis, with a preserved adaptive mechanism to chronic stress.

scholarly journals Testosterone-dependent variations in plasma and intrapituitary corticosteroid binding globulin and stress hypothalamic-pituitary-adrenal activity in the male rat

2004 ◽  
Vol 181 (2) ◽  
pp. 223-231 ◽  
Author(s):  
V Viau ◽  
MJ Meaney
Keyword(s):  
Feedback Regulation ◽  
High Plasma ◽  
Male Rats ◽  
Testosterone Replacement ◽  
Male Rat ◽  
Plasma Testosterone ◽  
Hypothalamic Pituitary Adrenal ◽  
Corticosteroid Binding Globulin ◽  
Low Testosterone

Hypothalamic-pituitary-adrenal (HPA) activity is governed by glucocorticoid negative feedback and the magnitude of this signal is determined, in part, by variations in plasma corticosteroid-binding globulin (CBG) capacity. Here, in gonadectomized male rats we examine the extent to which different testosterone replacement levels impact on CBG and HPA function. Compared with gonadectomized rats with low testosterone replacement ( approximately 2 ng/ml), plasma adrenocorticotropin and beta-endorphin/beta-lipotropin responses to restraint stress were reduced in gonadectomized rats with high testosterone replacement ( approximately 5 ng/ml). Plasma CBG levels also varied negatively as a function of testosterone concentration. Moreover, glucocorticoid receptor binding in the liver was elevated by higher testosterone replacement, suggesting that testosterone acts to enhance glucocorticoid suppression of CBG synthesis. Since pituitary intracellular CBG (or transcortin) is derived from plasma, this prompted us to examine whether transcortin binding was similarly responsive to different testosterone replacement levels. Transcortin binding was lower in gonadectomized rats with high plasma testosterone replacement ( approximately 7 ng/ml) than in gonadectomized rats with low testosterone replacement ( approximately 2 ng/ml). This testosterone-dependent decrease in pituitary transcortin was associated, in vitro, with an enhanced nuclear uptake of corticosterone. These findings indicate that the inhibitory effects of testosterone on corticotrope responses to stress may be linked to decrements in plasma and intrapituitary CBG. This could permit greater access of corticosterone to its receptors and enhance glucocorticoid feedback regulation of ACTH release and/or proopiomelanocortin processing.

Sex-steroid receptors in the diethylnitrosamine model of hepatocarcinogenesis: modifications by gonadal ablation and steroid replacement therapy

1989 ◽  
Vol 3 (3) ◽  
pp. 229-237 ◽  
Author(s):  
S. Tejura ◽  
G. R. Rodgers ◽  
M. H. Dunion ◽  
M. A. Parsons ◽  
J. C. E. Underwood ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Androgen Receptors ◽  
Receptor Expression ◽  
Androgen Receptor Expression ◽  
Female Rats ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Sex Steroid ◽  
Oestrogen Receptors ◽  
Liver Tumours

ABSTRACT The results of this study confirm our previous report of increased androgen receptor expression in livers of female SUAH Wistar rats during development of liver tumours induced by diethylnitrosamine (DENA). In adult female rats not treated with DENA, removal of the ovary increased liver androgen receptor levels but testosterone did not further enhance the androgen receptor status of ovariectomized rats. In normal adult males the testis and/or testosterone maintained high levels of androgen receptors but oestrogen reduced them in castrated rats. Oestrogen receptor levels were not significantly changed in either males or females by gonadectomy. Treatment of female rats with DENA for 10 and 16 weeks increased liver androgen receptors but oestrogen receptors were only reduced by 16 weeks of DENA treatment, whether the rats were intact or ovariectomized. Concentrations of liver androgen receptors were increased in intact and castrated male rats by 10 and 16 weeks of DENA treatment, an increase not seen in the previous experiments. Oestrogen appeared to inhibit both the increases in liver androgen receptor expression and liver tumour development in rats treated with the weakly carcinogenic dose of 10 weeks of DENA. However, the full carcinogenic dose of 16 weeks of DENA increased liver androgen receptors and decreased oestrogen receptors in female rats regardless of sex-steroid status. Development of malignant hepatocellular carcinoma (HCC) was associated with both an increase in liver androgen receptors and a decrease in oestrogen receptors. Maintenance of relatively high levels of liver oestrogen receptors appeared to protect the liver against development of HCC.

scholarly journals Regulation of the Hypothalamic-Pituitary-Adrenal Axis Circadian Rhythm by Endocannabinoids Is Sexually Diergic

Endocrinology ◽  
2010 ◽  
Vol 151 (8) ◽  
pp. 3720-3727 ◽  
Author(s):  
Helen C. Atkinson ◽  
James D. Leggett ◽  
Susan A. Wood ◽  
Emma S. Castrique ◽  
Yvonne M. Kershaw ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Cannabinoid Receptor ◽  
Time Of Day ◽  
Female Rats ◽  
Male Rats ◽  
Acute Administration ◽  
Sampling System ◽  
Hypothalamic Pituitary Adrenal ◽  
Male And Female Rats ◽  
Cb1 Antagonist

We have examined the effects of acute administration of the cannabinoid receptor type 1 (CB1) antagonist AM251 on the rat hypothalamic-pituitary-adrenal (HPA) axis with respect to both gender and time of day. Blood samples were collected from conscious male and female rats every 5 min using an automated blood sampling system, and corticosterone concentrations were determined. In male rats, there was a distinct diurnal effect of AM251 with a greater activation of the HPA axis in the morning (diurnal trough) compared with the evening (diurnal peak). At both times of the day, circulating corticosterone concentrations were elevated for approximately 4 h after AM251 administration. In female rats, there was also diurnal variation in the activation of the HPA axis; however, these effects were not as profound as those in males. Corticosterone concentrations were only slightly elevated at the diurnal trough and for a shorter time period than in males (2 compared with 4 h). Moreover, there was no effect of AM251 on corticosterone concentrations when administered at the diurnal peak. Subsequent studies, only in males, in which both ACTH and corticosterone were measured, confirmed that the effects of AM251 on corticosterone were mediated by ACTH. Moreover, the elevation of both ACTH and corticosterone could be replicated using another CB1 antagonist, AM281. These data demonstrate that the extent and duration of HPA axis activation after CB1 blockade are clearly dependent on both gender and time of day.

scholarly journals Neuropeptide S Stimulates the Hypothalamo-Pituitary-Adrenal Axis and Inhibits Food Intake

Endocrinology ◽  
2006 ◽  
Vol 147 (7) ◽  
pp. 3510-3518 ◽  
Author(s):  
Kirsty L. Smith ◽  
Michael Patterson ◽  
Waljit S. Dhillo ◽  
Sejal R. Patel ◽  
Nina M. Semjonous ◽  
...  
Keyword(s):  
Food Intake ◽  
Hpa Axis ◽  
Paraventricular Nucleus ◽  
Arginine Vasopressin ◽  
Lateral Ventricle ◽  
Neuropeptide S ◽  
Plasma Acth ◽  
Vasopressin Release ◽  
Pituitary Adrenal Axis ◽  
Stimulation Of

Neuropeptide S (NPS) is a recently discovered peptide shown to be involved in the modulation of arousal and fear responses. It has also been shown that lateral ventricle administration of NPS causes a significant decrease in food intake. Neuropeptides involved in the modulation of arousal have been shown to be involved in the regulation of the hypothalamo-pituitary adrenal (HPA) axis and food intake. In this study, we have examined the effect of intracerebroventricular (ICV) administration of NPS on behavior, regulation of the HPA axis, and food intake. ICV NPS significantly increased plasma ACTH and corticosterone 10 and 40 min after injection, respectively. A single ICV injection of NPS caused a significant increase in rearing activity as well as ambulatory movement for up to 45 min after injection. We then studied the effect of paraventricular nucleus (PVN) administration of NPS on the regulation of the HPA axis, behavior, and food intake. There was a significant increase in plasma ACTH and corticosterone after a single NPS PVN injection. Incubation of hypothalamic explants with increasing concentrations of NPS caused a significant increase in CRH and arginine vasopressin release. In addition, PVN administration of NPS dose-dependently inhibited food intake in the first hour after injection, although no effect on food intake was seen after this time. PVN administration of NPS caused a significant increase in rearing activity. These data demonstrate a novel role for NPS in the stimulation of the HPA axis.

Prenatal exposure to dexamethasone alters hippocampal drive on hypothalamic-pituitary-adrenal axis activity in adult male rats

2006 ◽  
Vol 290 (5) ◽  
pp. R1366-R1373 ◽  
Author(s):  
Jennifer A. Shoener ◽  
Romana Baig ◽  
Kathleen C. Page
Keyword(s):  
Hpa Axis ◽  
Adult Male ◽  
Restraint Stress ◽  
Exposed Group ◽  
Late Gestation ◽  
Male Rats ◽  
Mrna Levels ◽  
Hypothalamic Pituitary Adrenal ◽  
Hpa Axis Activity ◽  
Circulating Levels

Glucocorticoids are essential for normal hypothalamic-pituitary-adrenal (HPA) axis activity; however, recent studies warn that exposure to excess endogenous or synthetic glucocorticoid during a specific period of prenatal development adversely affects HPA axis stability. We administered dexamethasone (DEX) to pregnant rats during the last week of gestation and investigated subsequent HPA axis regulation in adult male offspring in unrestrained and restraint-stressed conditions. With the use of real-time PCR and RIA, we examined the expression of regulatory genes in the hippocampus, hypothalamus, and pituitary, including corticotropin-releasing hormone (CRH), arginine vasopressin (AVP), glucocorticoid receptors (GR), mineralcorticoid receptors (MR), and 11-β-hydroxysteroid dehydrogenase-1 (11β-HSD-1), as well as the main HPA axis hormones, adrenal corticotropic hormone (ACTH) and corticosterone (CORT). Our results demonstrate that the DEX-exposed group exhibited an overall change in the pattern of gene expression and hormone levels in the unrestrained animals. These changes included an upregulation of CRH in the hypothalamus, a downregulation of MR with a concomitant upregulation of 11β-HSD-1 in the hippocampus, and an increase in circulating levels of both ACTH and CORT relative to unrestrained control animals. Interestingly, both DEX-exposed and control rats exhibited an increase in pituitary GR mRNA levels following a 1-h recovery from restraint stress; however, the increased expression in DEX-exposed rats was significantly less and was associated with a slower return to baseline CORT compared with controls. In addition, circulating levels of ACTH and CORT as well as hypothalamic CRH and hippocampal 11β-HSD-1 expression levels were significantly higher in the DEX-exposed group compared with controls following restraint stress. Taken together, these data demonstrate that late-gestation DEX exposure in rats is associated with persistent changes in both the modulation of HPA axis activity and the HPA axis-mediated response to stress.

scholarly journals Effect of vasopressin 1b receptor blockade on the hypothalamic–pituitary–adrenal response of chronically stressed rats to a heterotypic stressor

2008 ◽  
Vol 200 (3) ◽  
pp. 285-291 ◽  
Author(s):  
Francesca Spiga ◽  
Louise R Harrison ◽  
Cliona P MacSweeney ◽  
Fiona J Thomson ◽  
Mark Craighead ◽  
...  
Keyword(s):  
White Noise ◽  
Chronic Stress ◽  
Hpa Axis ◽  
Home Cage ◽  
Male Rats ◽  
Receptor Blockade ◽  
Hypothalamic Pituitary Adrenal ◽  
Corticosterone Secretion ◽  
Corticosterone Response ◽  
Adrenal Response

Exposure to chronic restraint (CR) modifies the hypothalamic–pituitary–adrenal (HPA) axis response to subsequent acute stressors with adaptation of the response to a homotypic and sensitization of the response to a heterotypic stressor. Since vasopressin (AVP) activity has been reported to change during chronic stress, we investigated whether this was an important factor in HPA facilitation. We therefore tested whether vasopressin 1b receptor (AVPR1B) blockade altered the ACTH and corticosterone response to heterotypic stressors following CR stress. Adult male rats were exposed to CR, single restraint, or were left undisturbed in the home cage. Twenty-four hours after the last restraint, rats were injected with either a AVPR1B antagonist (Org, 30 mg/kg, s.c.) or vehicle (5% mulgofen in saline, 0.2/kg, s.c.) and then exposed to either restraint, lipopolysaccharide (LPS) or white noise. CR resulted in the adaptation of the ACTH and corticosterone response to restraint and this effect was not prevented by pretreatment with Org. Although we found no effect of CR on LPS-induced ACTH and corticosterone secretion, both repeated and single episodes of restraint induced the sensitization of the ACTH, but not corticosterone response to acute noise. Pretreatment with Org reduced the exaggerated ACTH response to noise after both single and repeated exposure to restraint.

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