The fetal placental hypothalamic–pituitary–adrenal (HPA) axis, parturition and post natal health

Challis, John; Sloboda, Deborah M.; Matthews, Stephen G.; Holloway, A.; Alfaidy, Nadia; Patel, Falguni A.; Whittle, WL; Fraser, Mhoyra; Moss, Timothy; Newnham, John P.

doi:10.1016/s0303-7207(01)00624-4

Cited by 282 publications

(172 citation statements)

References 32 publications

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“…Therefore, factors that induce miscarriages might regulate activities of those enzymes. Although not all the etiologies nor mechanisms of a miscarriage are well defined, all the causes might be linked to endogenous glucocorticoids, key steroid hormones, involved in stress responses and essential for the maturation of fetal organs, growth, and preparation of the fetus for birth (34,35). This study found that dexamethasone negatively regulated lipoxygenases in LPS-induced murine miscarriages, a finding consistent and in line with previous reports (18)(19)(20).…”

Section: Discussionsupporting

confidence: 91%

Spontaneous Miscarriages Are Explained by the Stress/Glucocorticoid/Lipoxin A4 Axis

Xu¹,

Zhao

Zhang

et al. 2013

The Journal of Immunology

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Despite various suspected causes, ranging from endocrine and genetic to infectious and immunological aspects, the molecular mechanisms of miscarriage still remain enigmatic. This work provides evidence that downregulation of 11β-hydroxysteroid dehydrogenase (HSD) type 2, the key enzyme inactivating glucocorticoid activities, insults the pregnant inflammatory milieu by inhibiting the biosynthesis of lipoxin A4 (LXA4), a metabolite of arachidonic acid, leading to an early loss of the pregnancy. Both LXA4 and its biosynthetic enzymes were found to be decreased in women with spontaneous miscarriages and in the murine miscarriage model. Replenishing LXA4 reversed LPS-induced miscarriages in mouse models, whereas blocking LXA4 signaling resulted in miscarriages in the pregnant mice. The protective effect of LXA4 might be explained by LXA4’s role in regulating uterine and placental inflammatory factors and mast cells. The underlying molecular mechanism involved miscarriage-inducing infections or stresses that downregulate the expression of 11β-HSD2, but not 11β-HSD1, resulting in increases in glucocorticoid activity and decreases in LXA4. Together, these findings suggest that the stress/glucocorticoid/LXA4 axis might be a common pathway through which miscarriages occur.

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Section: Discussionsupporting

confidence: 91%

Spontaneous Miscarriages Are Explained by the Stress/Glucocorticoid/Lipoxin A4 Axis

Xu¹,

Zhao

Zhang

et al. 2013

The Journal of Immunology

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“…Research into the interplay between the HPA axis and metabolism suggests that the relationship between these systems is established during the prenatal and early postnatal period (3,10,39,53), and maternal stress experienced by the fetus during gestation has proven developmental and metabolic effects (26,34,37,38). Persistent stress also influences bone function, with chronic elevations of cortisol leading to low bone mineral in humans (12).…”

Section: Discussionmentioning

confidence: 99%

Short-term voluntary exercise in the rat causes bone modeling without initiating a physiological stress response

Rosa¹,

Firth²,

Blair³

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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research has revealed a neuroendocrine connection between the skeleton and metabolism. Exercise alters both bone modeling and energy balance and may be useful in further developing our understanding of this complex interplay. However, research in this field requires an animal model of exercise that does not cause a physiological stress response in the exercised subjects. In this study, we develop a model of short-term voluntary exercise in the female rat that causes bone modeling without causing stress. Rats were randomly assigned to one of three age-matched groups: control, tower climbing, and squat exercise (rising to an erect bipedal stance). Exercise for 21 days resulted in bone modeling as assessed by peripheral quantitative computed tomography. Fecal corticosterone output was used to assess physiological stress at three time points during the study (preexercise, early exercise, and late in the exercise period). There were no differences in fecal corticosterone levels between groups or time points. This model of voluntary exercise in the rat will be useful for future studies of the influence of exercise on the relationship between skeletal and metabolic health and may be appropriate for investigation of the developmental origins of those effects. computed tomography; corticosterone; exercise; metabolism; stress RECENT ADVANCES IN OUR UNDERSTANDING of the dynamic relationship between body structure and metabolism have revealed a neuroendocrine connection between bone remodeling and energy balance, with both bone and fat acting as endocrine organs (14). The osteoblast-specific protein osteocalcin regulates glucose handling through effects on insulin secretion and sensitivity (33). This action is in turn mediated by the adipokine leptin, which inhibits insulin secretion through direct effects on pancreatic ␤-cells (18) and through inhibition of osteocalcin activity (25). The interplay between bone and metabolism has recently been further elucidated by the discovery that the Forkhead family transcription factor FoxO1, a key regulator of insulin handling in multiple tissues, also acts within the osteoblast to control osteocalcin expression and bioactivity (46).Exercise stimulates modeling of the musculoskeletal system (19, 55, 65), alters metabolism (40), and enhances brain function (17), and thus exercise provides an excellent means of exploring the neuroendocrine connection between bone, fat, and energy balance. The rat model of exercise has been used extensively to study the physiological effects of physical activity using such exercise modalities as swimming (24, 32), running (20,29,41,49,52), jumping (57), tower climbing (43), rising to an erect bipedal stance (11, 64), and weight lifting (62). The effects of exercise on bone have been widely characterized in the rat. Ovariectomized rats undergo changes in bone structure that are nearly identical to those seen in human osteoporosis (28,42), and these animals have proven useful for the study of exercise interventions in osteoporosis treatment (36).In examini...

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“…It has been shown that the hypothalamo-pituitary adrenal axis in sheep becomes functional during fetal life (Brooks et al 1992, McMillen et al 1995, Matthews & Challis 1996, Reperant & Durand 1997, Challis et al 2001. A steady increase in circulating concentrations of cortisol towards the end of gestation has an important role in the maturation of the fetal organ systems and in triggering parturition (Matthews & Challis 1996, Reperant & Durand 1997, Challis et al 2001.…”

Section: Introductionmentioning

confidence: 99%

“…A steady increase in circulating concentrations of cortisol towards the end of gestation has an important role in the maturation of the fetal organ systems and in triggering parturition (Matthews & Challis 1996, Reperant & Durand 1997, Challis et al 2001. It is also clear that the fetal hypothalamo-pituitary adrenal axis is capable of responding to acute stress during late gestation.…”

Section: Introductionmentioning

confidence: 99%

A sex difference in the cortisol response to tail docking and ACTH develops between 1 and 8 weeks of age in lambs

Turner

Hosking²,

Parr³

et al. 2006

Journal of Endocrinology

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It is important to understand factors that may influence responses to stress, as these factors may also influence vulnerability to pathologies that can develop when stress responses are excessive or prolonged. It is clear that, in adults, the sex of an individual can influence the cortisol response to stress in a stressor specific manner. Nevertheless, the stage of development at which these sex differences emerge is unknown. We tested the hypothesis that there are sex differences in the cortisol response to tail docking and ACTH in lambs of 1 and 8 weeks of age. We also established cortisol responses in males when tail docking was imposed alone and in combination with castration at these ages. In experiment 1, 1 and 8 week old male and female lambs were subjected to sham handling, tail docking or, in males, a combination of tail docking and castration. In experiment 2, we administered ACTH (1·0 IU/kg) to male and female lambs at 1 and 8 weeks of age. There were significant cortisol responses to all treatments at both ages. Sex differences in the cortisol responses to tail docking and ACTH developed between 1 and 8 weeks of age, with females having greater responses than males. The data suggest that the mechanism for the sex difference in response to tail docking may involve the adrenal glands. At both ages, in males, the cortisol response to the combined treatment of tail docking and castration was significantly greater than that for tail docking alone.

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The fetal placental hypothalamic–pituitary–adrenal (HPA) axis, parturition and post natal health

Cited by 282 publications

References 32 publications

Spontaneous Miscarriages Are Explained by the Stress/Glucocorticoid/Lipoxin A4 Axis

Spontaneous Miscarriages Are Explained by the Stress/Glucocorticoid/Lipoxin A4 Axis

Short-term voluntary exercise in the rat causes bone modeling without initiating a physiological stress response

A sex difference in the cortisol response to tail docking and ACTH develops between 1 and 8 weeks of age in lambs

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