Estrogen potentiates adrenocortical responses to stress in female rats

Figueiredo, Helmer F.; Ulrich‐Lai, Yvonne M.; Choi, Dennis C.; Herman, James P.

doi:10.1152/ajpendo.00102.2006

Cited by 155 publications

(126 citation statements)

References 66 publications

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“…This apparent decoupling of circulating ACTH and corticosterone suggests that factors outside the conventional HPA axis influence plasma corticosterone in pregnancy. For example, enhanced adrenal responsiveness appears to drive increased maternal corticosterone levels after mid-gestation in the rat (Atkinson & Waddell 1995), an effect likely mediated via rising estrogen levels (Atkinson & Waddell 1997, Figueiredo et al 2007). Other 'non-HPA axis' factors that could enhance maternal levels of corticosterone include a fall in its metabolic clearance rate due to higher plasma corticosteroid-binding globulin (CBG) levels (Gala & Westphal 1967, Douglas et al 2003 or a contribution from the fetal adrenal.…”

Section: Discussionmentioning

confidence: 99%

Pregnancy-induced adaptations of the central circadian clock and maternal glucocorticoids

Wharfe¹,

Mark²,

Wyrwoll³

et al. 2015

Journal of Endocrinology

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Maternal physiological adaptations, such as changes to the hypothalamic-pituitary-adrenal (HPA) axis, are central to pregnancy success. Circadian variation of the HPA axis is dependent on clock gene rhythms in the hypothalamus, but it is not known whether pregnancy-induced changes in maternal glucocorticoid levels are mediated via this central clock. We hypothesized that hypothalamic expression of clock genes changes across mouse pregnancy and this is linked to altered HPA activity. The anterior hypothalamus and maternal plasma were collected from C57Bl/6J mice prior to pregnancy and on days 6, 10, 14 and 18 of gestation (termZd19), across a 24-h period (0800, 1200, 1600, 2000, 0000, 0400 h). Hypothalamic expression of clock genes and Crh was determined by qPCR, plasma ACTH concentration measured by Milliplex assay and plasma corticosterone concentration by LC-MS/MS. Expression of all clock genes varied markedly across gestation, most notably at mid-gestation when levels of each gene were elevated. The pregnancy-induced increase in maternal corticosterone levels (by up to 14-fold on day 14) was not accompanied by a parallel shift in plasma ACTH (28% lower on day 14 compared with non-pregnant levels). Moreover, while circadian rhythmicity in corticosterone was maintained up to day 14 of gestation, this was effectively lost by day 18. Overall, our data show that the central circadian clock undergoes marked adaptations throughout mouse pregnancy, changes that are likely to contribute to maternal physiological adaptations. Importantly, however, neither hypothalamic clock genes nor plasma ACTH levels appear to drive the marked increase in maternal corticosterone after mid-gestation.

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Section: Discussionmentioning

confidence: 99%

Pregnancy-induced adaptations of the central circadian clock and maternal glucocorticoids

Wharfe¹,

Mark²,

Wyrwoll³

et al. 2015

Journal of Endocrinology

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“…Estrous data collection was not incorporated into the present study, however, many studies have concluded that estrogen is a key factor for sex differences in response to stress [7,12,56]. For example, estradiol [57] or estrogen [56] treatment enhances corticosterone release in response to stress. While a previous study reported motor function to be more susceptible to arousal in women than in men [46], the physiological stress response usually seems to be greater in males [58,59].…”

Section: Discussionmentioning

confidence: 99%

Sex differences in skilled movement in response to restraint stress and recovery from stress

Jadavji

Metz

2008

Behavioural Brain Research

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Sex differences exist in skilled movement, and skilled motor performance is also influenced by stress. As shown for cognitive function, the effects of stress are usually characterized by considerable sexual dimorphism. The purpose of this study was to investigate sex differences in skilled motor function in response to stress. Male and female Long-Evans rats were trained and tested in skilled reaching and skilled walking tasks. Both groups of animals were then exposed to daily restraint stress for 15 days. Recovery from daily stress was assessed by comparing reaching performance at 10 min versus 60 min after restraint stress, and recovery from chronic stress was tested for 21 days after cessation of stress. Animals were tested daily in skilled reaching for the entire period. Observations showed that females performed significantly better than males during the stress period in terms of reaching success and number of attempts needed to grasp a food pellet. No difference between testing at 10 or 60 min after daily stress was found. Analysis of movement patterns and recovery from stress indicated that males and females use different strategies to overcome stress-induced motor disturbance. While male rats preferred to use original movement patterns, females tended to modify these patterns in order to increase reaching success. Modification of movement patterns in female rats was accompanied by a faster recovery in success rate after the cessation of stress. These results indicate sex differences in skilled reaching in response to stress, and in the recovery period after stress.

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“…Finasteride and naloxone, alone or combined, fully restored the corticosterone profile but not the ACTH levels to the virgin values. Enhanced sensitivity to ACTH as a result of high estrogen levels in pregnancy can explain such lack of fidelity between the ACTH and corticosterone responses (Figueiredo et al, 2007). The capacity of the anterior pituitary to generate an ACTH response to stress is not reduced in late pregnancy , indicating that some central HPA elements remain hypoactive even after finasteride and naloxone treatment.…”

Section: Allopregnanolone-synthesizing Enzymesmentioning

confidence: 99%

Central Opioid Inhibition of Neuroendocrine Stress Responses in Pregnancy in the Rat Is Induced by the Neurosteroid Allopregnanolone

Brunton¹,

McKay²,

et al. 2009

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The hypothalamus-pituitary-adrenal (HPA) axis is the major neuroendocrine stress response system. Corticotropin-releasing hormone (CRH) neurons in the parvocellular paraventricular nucleus (pPVN) play a key role in coordinating responses of this system to stressors. The cytokine interleukin-1␤ (IL-1␤), mimicking infection, robustly activates these CRH neurons via a noradrenergic input arising from the nucleus tractus solitarii (NTS). In late pregnancy, HPA axis responses to stressors, including IL-1␤, are attenuated by a central opioid mechanism that auto-inhibits noradrenaline release in the PVN. Here we show that the neuroactive progesterone metabolite allopregnanolone induces these changes in HPA responsiveness to IL-1␤ in pregnancy. In late pregnancy, inhibition of 5␣-reductase (an allopregnanolone-synthesizing enzyme) with finasteride restored HPA axis responses (rapidly increased pPVN CRH mRNA expression, ACTH, and corticosterone secretion) to IL-1␤. Conversely, allopregnanolone reduced HPA responses in virgin rats. In late pregnancy, activity of the allopregnanolone-synthesizing enzymes (5␣-reductase and 3␣-hydroxysteroid dehydrogenase) was increased in the hypothalamus as was mRNA expression in the NTS and PVN. Naloxone, an opioid antagonist, restores HPA axis responses to IL-1␤ in pregnancy but had no additional effect after finasteride, indicating a causal connection between allopregnanolone and the endogenous opioid mechanism. Indeed, allopregnanolone induced opioid inhibition over HPA responses to IL-1␤ in virgin rats. Furthermore, in virgin rats, allopregnanolone treatment increased, whereas in pregnant rats finasteride decreased proenkephalin-A mRNA expression in the NTS. Thus, in pregnancy, allopregnanolone induces opioid inhibition over HPA axis responses to immune challenge. This novel opioid-mediated mechanism of allopregnanolone action may alter regulation of other brain systems in pregnancy.

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Estrogen potentiates adrenocortical responses to stress in female rats

Cited by 155 publications

References 66 publications

Pregnancy-induced adaptations of the central circadian clock and maternal glucocorticoids

Pregnancy-induced adaptations of the central circadian clock and maternal glucocorticoids

Sex differences in skilled movement in response to restraint stress and recovery from stress

Central Opioid Inhibition of Neuroendocrine Stress Responses in Pregnancy in the Rat Is Induced by the Neurosteroid Allopregnanolone

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