Sex difference in resting pituitary-adrenal function in the rat

Critchlow, V.; Liebelt, Robert A.; Bar-Sela, Mildred Elwers; Mountcastle, W.; Lipscomb, H. S.

doi:10.1152/ajplegacy.1963.205.5.807

Cited by 503 publications

(229 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: 66%

“…To date, the focus has been on elements of the HPA axis. Although there is substantial evidence for such a sexual differentiation in HPA sensitivity in rats (Kitay, 1961;Critchlow et al, 1963;Le Mevel et al, 1979;Seale et al, 2004), this distinction is less clear in humans. Indeed, certain studies suggest that HPA drive is greater in males compared to females under certain conditions (Kirschbaum et al, 1999;Kudielka et al, 1998;Seeman et al, 2001;Traustadottir et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…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: 86%

“…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: 99%

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

Curtis

Bethea

Valentino

2005

Neuropsychopharmacol

192

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: 66%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 86%

Section: Sex Differences In Hpa Vs Lc Sensitivity To Stressmentioning

confidence: 99%

See 2 more Smart Citations

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

Curtis

Bethea

Valentino

2005

Neuropsychopharmacol

192

196

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“…Supportive data include observations of sex differences in hypothalamic-pituitaryadrenal (HPA) axis activity/responsivity (Kitay, 1961b;Brett et al, 1983;Horrocks et al, 1990;Kirschbaum et al, 1992;McCormick et al, 2002;Roelfsema et al, 1993;Greenspan et al, 1993) and demonstration of acute regulatory effects of gonadal steroids on the HPA axis in animal castration and replacement studies (Kitay, 1963;Burgess and Handa, 1992;Critchlow et al, 1963;Bingaman et al, 1994). As the first observations of sex differences showed increased HPA axis activity in female rodents, most attention has focused on the effects of estradiol, with little attention paid to the possible modulatory role of testosterone.…”

Section: Introductionmentioning

confidence: 99%

Testosterone Suppression of CRH-Stimulated Cortisol in Men

Rubinow

Roca

Schmidt

et al. 2005

Neuropsychopharmacol

134

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Despite observations of age-dependent sexual dimorphisms in hypothalamic-pituitary-adrenal (HPA) axis activity, the role of androgens in the regulation of HPA axis activity in men has not been examined. We assessed this role by performing CRH stimulation tests in 10 men (ages 18-45 years) during gonadal suppression with leuprolide acetate and during testosterone addition to leuprolide. CRHstimulated cortisol levels as well as peak cortisol and greatest cortisol excursion were significantly lower (po0.05, 0.005, and 0.01, respectively) during testosterone replacement compared with the induced hypogonadal condition (leuprolide plus placebo); cortisol area under the curve was lower at a trend level (po0.1). Paradoxically, CRH-stimulated corticotropin (ACTH) was increased significantly during testosterone replacement (po0.05). The cortisol : ACTH ratio, a measure of adrenal sensitivity, was lower during testosterone replacement (po0.1). A mixed effects regression model showed that testosterone but not estradiol or CBG significantly contributed to the variance of cortisol. These data demonstrate that testosterone regulates CRH-stimulated HPA axis activity in men, with the divergent effects on ACTH and cortisol suggesting a peripheral (adrenal) locus for the suppressive effects on cortisol. Our results further demonstrate that the enhanced stimulated HPA axis activity previously described in young men compared with young women cannot be ascribed to an activational upregulation of the axis by testosterone.

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Arcuate nucleus of the hypothalamus: Effects of age and sex

Leal¹,

Andrade²,

Paula‐Barbosa³

et al. 1998

J. Comp. Neurol.

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The arcuate nucleus of the hypothalamus (ARN) is involved in a variety of functions known to be sexually dimorphic and altered by aging. Although the effects of sex and age on the synaptic organization and neurochemistry of the ARN have been extensively analyzed, data regarding sex-related differences and age-induced effects on the total number of neurons and volume of the ARN in adult and aged male and female rats are controversial. To address this issue, we have quantitatively analyzed the ARN of male and female Wistar rats aged 6 and 24 months. The optical fractionator, the optical rotator, and the Principle of Cavalieri were used as the estimators of the total number of neurons, mean nuclear volume of ARN neurons, and volume of the ARN, respectively. In addition, a Golgi study was carried out to analyze the dendritic trees of its neurons. We found that in young adult rats, the volume of the ARN is 0.9 mm3 in males and 0.7 mm3 in females, whereas the total number of neurons is 100 x 10(3) in males and 86 x 10(3) in females. ARN neurons of males and females have identical mean nuclear volumes, which we estimated to be 300 microm3. No significant effects of age were found in these parameters, both in males and in females. In adult rats, no sex-related differences were detected in the number of dendritic segments and in the total dendritic length, but the dendritic branching density and the spine density were greater in females than in males. In aged rats there was a significant reduction in the number of dendritic segments, in the total dendritic length, and in the branching and spine densities that, although evident in both sexes, was more marked in females. Our results show that the total number of neurons and the volume of the ARN are sexually dimorphic in adult and aged rats and that neither of these parameters is altered by aging. Conversely, aging induces regressive changes in the dendritic arborizations of ARN neurons of males and females and abolishes the sexual dimorphic pattern of their organization.

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Sex difference in resting pituitary-adrenal function in the rat

Cited by 503 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

Testosterone Suppression of CRH-Stimulated Cortisol in Men

Arcuate nucleus of the hypothalamus: Effects of age and sex

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