Sex Differences in the HPA Axis

Goel, Nirupa; Workman, Joanna L.; Lee, Tiffany T.; Innala, Leyla; Viau, Victor

doi:10.1002/cphy.c130054

Cited by 331 publications

(233 citation statements)

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“…It is well known that adrenocortical activity in the rat, like in other mammals, is sensitive to androgens and estrogens [1,24,25]. These hormones may affect adrenal cortex growth and function either via central pathways (hypothalamic CRH and adenohypophyseal ACTH) or -with great probability -directly, via specific receptors expressed in the cortex and/or by interfering with adrenocortical enzymes, among them those involved in steroidogenesis.…”

Section: Discussionmentioning

confidence: 99%

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Expression of estrogen, estrogen related and androgen receptors in adrenal cortex of intact adult male and female rats

Trejter

Jopek

Celichowski

et al. 2015

Folia Histochem Cytobiol.

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Introduction. Adrenocortical activity in various species is sensitive to androgens and estrogens. They may affect adrenal cortex growth and functioning either via central pathways (CRH and ACTH) or directly, via specific receptors expressed in the cortex and/or by interfering with adrenocortical enzymes, among them those involved in steroidogenesis. Only limited data on expression of androgen and estrogen receptors in adrenal glands are available. Therefore the present study aimed to characterize, at the level of mRNA, expression of these receptors in specific components of adrenal cortex of intact adult male and female rats. Material and methods. Studies were performed on adult male and female (estrus) Wistar rats. Total RNA was isolated from adrenal zona glomerulosa (ZG) and fasciculate/reticularis (ZF/R). Expression of genes were evaluated by means of Affymetrix ® Rat Gene 1.1 ST Array Strip and QPCR. Results. By means of Affymetrix ® Rat Gene 1.1 ST Array we examined adrenocortical sex differences in the expression of nearly 30,000 genes. All data were analyzed in relation to the adrenals of the male rats. 32 genes were differentially expressed in ZG, and 233 genes in ZF/R. In the ZG expression levels of 24 genes were lower and 8 higher in female rats. The more distinct sex differences were observed in the ZF/R, in which expression levels of 146 genes were lower and 87 genes higher in female rats. Performed analyses did not reveal sex differences in the expression levels of both androgen (AR) and estrogen (ER) receptor genes in the adrenal cortex of male and female rats. Therefore matrix data were validated by QPCR. QPCR revealed higher expression levels of AR gene both in ZG and ZF/R of male than female rats. On the other hand, QPCR did not reveal sex-related differences in the expression levels of ERa, ERb and non-genomic GPR30 (GPER-1) receptor. Of those genes expression levels of ERa genes were the highest. In studied adrenal samples the relative expression of ERa mRNA was higher than ERb mRNA. In adrenals of adult male and female rats expression levels of estrogen-related receptors ERRa and ERRb were similar, and only in the ZF/R of female rats ERRg expression levels were significantly higher than in males. We also analyzed expression profile of three isoforms of steroid 5a-reductase (Srd5a1, Srd5a2 and Srd5a3) and aromatase (Cyp19a1) and expression levels of all these genes were similar in ZG and ZF/R of male and female rats. Conclusions. In contrast to Affymetrix microarray data QPCR revealed higher expression levels of AR gene in adrenal glands of the male rats. In adrenals of both sexes expression levels of ERa, ERb, non-genomic GPR30 (GPER-1), ERRa and ERRb receptors were comparable. The obtained results suggest that acute steroidogenic effect of estrogens on corticosteroid secretion may be mediated by non-genomic GPR30.

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Section: Discussionmentioning

confidence: 99%

“…It is well documented that function of adrenal cortex in various species is modulated by androgens and estrogens [1,24,25]. In vivo their action is mainly indirect and involves modulation of the hypothalamo-pituitary-adrenocortical axis, affecting primarily CRH and ACTH synthesis and/or secretion.…”

Section: Discussionmentioning

confidence: 99%

Expression of estrogen, estrogen related and androgen receptors in adrenal cortex of intact adult male and female rats

Trejter

Jopek

Celichowski

et al. 2015

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

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“…In addition, given that sex hormones are implicated in the glucocorticoid response to acute stress, and that females generally produce greater stress hormones when in the luteal phase of the menstrual cycle [18], changes in hormonal output associated with aging suggest that sex difference in inflammatory stress responses may more consistently emerge in older participants. Heightened pro-inflammatory stress responses may therefore be a relevant sex-specific risk marker in middle-and older-aged individuals, but most previous studies have mainly included young subjects.…”

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confidence: 99%

Post-menopausal Women Exhibit Greater Interleukin-6 Responses to Mental Stress Than Older Men

2016

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Background Acute stress triggers innate immune responses and elevation in circulating cytokines including interleukin-6 (IL-6). The effect of sex on IL-6 responses remains unclear due to important limitations of previous studies. Purpose The purpose of this study was to examine sex differences in IL-6 responses to mental stress in a healthy, older (postmenopausal) sample accounting for several moderating factors. Methods Five hundred six participants (62.9 ± 5.60 years, 55 % male) underwent 10 min of mental stress consisting of mirror tracing and Stroop task. Blood was sampled at baseline, after stress, and 45 and 75 min post-stress, and assayed using a high sensitivity kit. IL-6 reactivity was computed as the mean difference between baseline and 45 min and between baseline and 75 min post-stress. Main effects and interactions were examined using ANCOVA models. Results There was a main effect of time for the IL-6 response (F 3,1512 = 201.57, p = <.0001) and a sex by time interaction (F 3,1512 = 17.07, p = <.001). In multivariate adjusted analyses, IL-6 reactivity was significantly greater in females at 45 min (M = 0.37 ± 0.04 vs. 0.20 ± 0.03 pg/mL, p = .01) and at 75 min (M = 0.57 ± 0.05 vs. 0.31 ± 0.05 pg/mL, p = .004) post-stress compared to males. Results were independent of age, adiposity, socioeconomic position, depression, smoking and alcohol consumption, physical activity, statin use, testing time, task appraisals, hormone replacement, and baseline IL-6. Other significant predictors of IL-6 reactivity were lower household wealth, afternoon testing, and baseline IL-6. Conclusions Healthy, post-menopausal females exhibit substantially greater IL-6 responses to acute stress. Inflammatory responses if sustained over time may have clinical implications for the development and maintenance of inflammatoryrelated conditions prevalent in older women.

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“…This is not surprising, given that sex differences in the development of HPA axis functioning have been well described previously [41,42] . Earlier analyses of the data used in the present study have revealed differential development of HPA axis functioning, with a tendency for attenuation among females during adolescence [29] .…”

Section: Discussionmentioning

confidence: 94%

The Interaction of Childhood Maltreatment, Sex, and Borderline Personality Features in the Prediction of the Cortisol Awakening Response in Adolescents

et al. 2017

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Aims: The study aimed to investigate childhood maltreatment, sex, and borderline personality disorder (BPD) symptoms as prospective predictors of adolescent hypothalamic-pituitary-adrenal (HPA) axis reactivity. Method: A sample of 69 adolescents (30 female and 39 male) were selected from a larger longitudinal study of adolescent development and assessed at 3 time points. BPD symptoms were assessed at T1 (approx. 12.5 years), childhood maltreatment was assessed at T2 (approx. 14.9 years), and multiple assessments of salivary cortisol (cortisol awakening response; CAR) were undertaken at T3 (approx. 15.5 years). Results: Multivariate linear regression analysis revealed a significant main effect for childhood maltreatment but not for early BPD symptoms as a predictor of lower CAR in adolescence (p = 0.047). The association between childhood maltreatment and attenuated CAR was moderated by both early BPD symptoms (p = 0.024; no childhood maltreatment-dependent attenuation of CAR in the presence of BPD symptoms) and sex (p = 0.012; childhood maltreatment-dependent attenuation of CAR in females only). Furthermore, a 3-way BPD × childhood maltreatment × sex interaction (p = 0.041) indicated that the moderating effect of BPD symptoms was present in females only. Conclusion: These findings indicate that attenuation of the HPA axis occurs as a response to early maltreatment rather than being related to the early occurrence of BPD pathology. Traumatized female individuals with BPD symptoms might bypass adaptive HPA axis attenuation.

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Sex Differences in the HPA Axis

Cited by 331 publications

References 405 publications

Expression of estrogen, estrogen related and androgen receptors in adrenal cortex of intact adult male and female rats

Expression of estrogen, estrogen related and androgen receptors in adrenal cortex of intact adult male and female rats

Post-menopausal Women Exhibit Greater Interleukin-6 Responses to Mental Stress Than Older Men

The Interaction of Childhood Maltreatment, Sex, and Borderline Personality Features in the Prediction of the Cortisol Awakening Response in Adolescents

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