SEX DIFFERENCES IN ADRENAL CORTICAL SECRETION IN THE RAT<sup>1</sup>

Kitay, Julian I.

doi:10.1210/endo-68-5-818

Cited by 535 publications

(234 citation statements)

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“…Previous studies documented an increased responsiveness of the HPA axis in female vs male rats (Kitay, 1961;Critchlow et al, 1963;Le Mevel et al, 1979;Seale et al, 2004). The present study is the first to demonstrate that, in parallel with the HPA axis, the brain NE system of female rats is more responsive to certain stressors.…”

Section: Discussionsupporting

confidence: 67%

“…The higher incidence of depression in females has led to speculation that hormonal influences on components of the HPA axis may contribute to dysfunctions. In support of this, rodent studies have demonstrated elevated basal and stressinduced corticosterone secretion in female rats (Kitay, 1961;Critchlow et al, 1963;Le Mevel et al, 1979;Seale et al, 2004). Moreover, estrogen has been demonstrated to impair glucocorticoid negative feedback (Burgess and Handa, 1992).…”

Section: Introductionmentioning

confidence: 85%

“…Although sex differences in HPA sensitivity appear to be hormone-dependent (Kitay, 1961;Critchlow et al, 1963;Le Mevel et al, 1979;Seale et al, 2004), sex differences in LC sensitivity to stress are independent of adult hormonal status. Sex differences in the LC response could arise from direct organizational actions of hormones on expression of CRF-R or components of the CRF-R signaling pathway in LC neurons during development.…”

Section: Sex Differences In Hpa Vs Lc Sensitivity To Stressmentioning

confidence: 98%

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Sexually Dimorphic Responses of the Brain Norepinephrine System to Stress and Corticotropin-Releasing Factor

Curtis

Bethea

Valentino

2005

Neuropsychopharmacol

193

196

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Stress-related psychiatric disorders are more prevalent in females than males, and this has been attributed to differences in stress sensitivity. As activation of the locus coeruleus (LC)-norepinephrine (NE) system is an important component of the stress response, this study compared LC responses to stress in female and male rats under different hormonal conditions in the halothane-anesthetized state. The mean basal LC discharge rate was similar between groups. However, the magnitude of LC activation elicited by hypotensive stress was substantially greater in females, regardless of hormonal status. The difference in stress sensitivity could be attributed to the differential postsynaptic sensitivity of LC neurons to corticotropin-releasing factor (CRF), which mediates LC activation by hypotension. CRF was 10-30 times more potent in activating LC neurons in female vs male rats. Interestingly, previous exposure to swim stress differentially regulated LC responses to CRF by sensitizing LC neurons of male, but not female, rats to CRF. The net effect of this was to abolish sex differences in LC sensitivity. Finally, CRF receptor (CRF-R) protein levels in the LC were greater in ovarectomized female vs male rats. This is the first study to demonstrate sex differences in the stress responsiveness of the brain noradrenergic system. Substantial sex differences were apparent in postsynaptic sensitivity to CRF and stress-induced regulation of postsynaptic sensitivity to CRF. These sex differences in the CRF regulation of the LC-NE system translate to a differential response to stress and may play a role in the increased vulnerability of females to stress-related psychiatric disorders.

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Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 85%

Section: Sex Differences In Hpa Vs Lc Sensitivity To Stressmentioning

confidence: 98%

See 1 more Smart Citation

Sexually Dimorphic Responses of the Brain Norepinephrine System to Stress and Corticotropin-Releasing Factor

Curtis

Bethea

Valentino

2005

Neuropsychopharmacol

193

196

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“…However, thymus weight did not change in response to estrogen in Experiment 5 or in response to tamoxifen treatment in Experiment 1. Since basal total corticosterone levels were not changed by estradiol or estradiol antagonists, and estradiol can raise corticosterone binding globulin (Kitay 1961), it is possible that estrogen treatment reduced free corticosterone levels. However, a reduction in free corticosterone would reduce, not enhance, glucocorticoid feedback, so it is unlikely that changes in corticosterone binding globulin contributed to our findings.…”

Section: Discussionmentioning

confidence: 99%

Effects of Estrogen Antagonists and Agonists on the ACTH Response to Restraint Stress in Female Rats

Young

Altemus

Parkison

et al. 2001

Neuropsychopharmacology

159

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Previous studies have found that female rats are less sensitive than males to hypothalamic-pituitary-adrenal axis feedback inhibition by exogenous glucocorticoid administration. To determine whether estrogen contributesSex differences in HPA axis regulation in rodents have been demonstrated by a number of investigators, and these differences are generally attributed to activational effects of gonadal steroids on elements of the hypothalamic-pituitary-adrenal axis in females, although there is also evidence that testosterone inhibits HPA axis activity in males (Handa et al. 1994). Female rats have higher levels of total plasma corticosterone (Kitay 1963). Female rats also have higher plasma corticosterone binding globulin levels, which likely contributes to findings of similar free corticosterone levels in male and female rats. Compared with male rats, female rats also have a greater ACTH response to stress, faster onset of corticosterone secretion after stress, and a faster rate of rise of corticosterone (Le Mevel et al. 1979;Jones et al. 1972; Young 1996). Several studies suggest that estradiol plays a role in enhanced stress responses in female

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“…Consistent with these findings, it could also be demonstrated in human studies that gender profoundly affects DEX/CRH test outcome (Heuser et al 1994;Zobel et al 2001). It has been reported that the activity of the HPA system varies with the level of sexual steroids during the estrous cycle (Viau and Meaney 1991) and during female reproduction (Lightman and Young 1989;Walker 1995; Neumann et al 1998a,b), and that there are differences between males and females (Kitay 1961;Rivier 1999;Neumann et al 2000). Interestingly, prenatal (Weinstock 1997) and postnatal (Wigger and Neumann 1999) stress altered HPA system responsiveness in adult male, but not female, offspring demonstrating a greater vulnerability in males than in females.…”

mentioning

confidence: 99%

Vasopressin Mediates the Response of the Combined Dexamethasone/CRH Test in Hyper-anxious Rats Implications for Pathogenesis of Affective Disorders

Keck

Wigger

Welt

et al. 2002

Neuropsychopharmacology

158

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To investigate the neuroendocrine alterations linked to inborn emotionality in two Wistar rat lines selectively bred for either high (HAB) or low (LAB) anxiety-related behavior, we administered the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH)testNeuroendocrine studies provide strong indications that hyperactivity of central corticotropin-releasing hormone (CRH) circuits, resulting in a characteristic dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system, plays a causal role in the symptomatology of affective and anxiety disorders (review: Keck and Holsboer 2001). The effects of CRH are modulated by vasopressin (AVP), which, after prolonged stress and in senescence, is increasingly coexpressed and secreted from hypothalamic CRH neurons in both humans and rodents (Antoni 1993;Tilders et al. 1993;Hatzinger et al. 2000;Keck et al. 2000). Similarly, increased numbers of CRH neurons that coexpress AVP mRNA have been found in the hypothalamus of depressed patients (Raadsheer et al. 1993;Purba et al. 1996). The excessive release of CRH and AVP into hypophysial portal blood is thought to increase the secretion of corticotropin (ACTH) from pituitary corticotrope cells, and this in turn to increase the release of corticosteroids from the adrenal gland. In this context, a variety of changes in HPA system regulation have been demonstrated in psychiatric disorders such as major depression, among them defective negative feedback of the HPA system, basal hypercortisolemia, inappropriate HPA suppression by the synthetic corticosteroid dexamethasone (DEX) and a paradoxical stimulation of ACTH secretion by CRH after DEX pretreatment (review: Holsboer and Barden 1996;Holsboer 2000). In depression, the combined DEX/CRH test, in which DEX-pretreated subjects receive a single dose of CRH, has proven to be the most sensitive tool for the detection of altered HPA regulation. Depending on age and gender, up to 90% of patients with depression show this neuroendocrine phenomenon (Heuser et al. 1994). Moreover, studies using the DEX/CRH test not only agree that normalization of an initial aberrance is predictive of a favorable treatment response but also corroborate other evidence that a persistent HPA abnormality correlates with chronicity or relapse (Heuser et al. 1996;Zobel et al. 1999). Since activation of corticosteroid receptors suppresses the synthesis and release of CRH and AVP from the hypothalamic paraventricular nucleus (PVN) , these findings are consistent with the hypothesis of functionally impaired corticosteroid receptor signaling in both depressed patients (Modell et al. 1997) and healthy subjects at genetic risk for depression Modell et al. 1998).As the mechanisms underlying the abnormal HPA reactivity in patients with certain psychiatric disorders are not fully understood, animal models are needed to further investigate the hypothesized linkage between these disorders and changes in the regulation of the HPA system. After several generations of selective breeding, we could establish ...

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SEX DIFFERENCES IN ADRENAL CORTICAL SECRETION IN THE RAT¹

Cited by 535 publications

References 0 publications

Sexually Dimorphic Responses of the Brain Norepinephrine System to Stress and Corticotropin-Releasing Factor

Sexually Dimorphic Responses of the Brain Norepinephrine System to Stress and Corticotropin-Releasing Factor

Effects of Estrogen Antagonists and Agonists on the ACTH Response to Restraint Stress in Female Rats

Vasopressin Mediates the Response of the Combined Dexamethasone/CRH Test in Hyper-anxious Rats Implications for Pathogenesis of Affective Disorders

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SEX DIFFERENCES IN ADRENAL CORTICAL SECRETION IN THE RAT1

Cited by 535 publications

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Sexually Dimorphic Responses of the Brain Norepinephrine System to Stress and Corticotropin-Releasing Factor

Sexually Dimorphic Responses of the Brain Norepinephrine System to Stress and Corticotropin-Releasing Factor

Effects of Estrogen Antagonists and Agonists on the ACTH Response to Restraint Stress in Female Rats

Vasopressin Mediates the Response of the Combined Dexamethasone/CRH Test in Hyper-anxious Rats Implications for Pathogenesis of Affective Disorders

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SEX DIFFERENCES IN ADRENAL CORTICAL SECRETION IN THE RAT¹