Physiology and Pathophysiology of the HPA Axis

Castro, Margaret de; Elias, Lucila Leico Kagohara; Elias, Paula Condé Lamparelli; Moreira, Ayrton Custódio

doi:10.1007/978-1-60327-449-4_1

Cited by 12 publications

(11 citation statements)

References 181 publications

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“…Glucocorticoids or glucocorticosteroids are produced by the adrenal cortex in response to cues such as stress or illness under the control of the HPA-axis. The name glucocorticoid is derived from their ability to promote gluconeogenesis in the liver and their synthesis in the adrenal cortex ( Castro et al, 2011 ). The natural human glucocorticoid is cortisol ( Figure 7 ).…”

Section: Steroid Hormonesmentioning

confidence: 99%

Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta

2018

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The steroid hormones progestagens, estrogens, androgens, and glucocorticoids as well as their precursor cholesterol are required for successful establishment and maintenance of pregnancy and proper development of the fetus. The human placenta forms at the interface of maternal and fetal circulation. It participates in biosynthesis and metabolism of steroids as well as their regulated exchange between maternal and fetal compartment. This review outlines the mechanisms of human placental handling of steroid compounds. Cholesterol is transported from mother to offspring involving lipoprotein receptors such as low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SRB1) as well as ATP-binding cassette (ABC)-transporters, ABCA1 and ABCG1. Additionally, cholesterol is also a precursor for placental progesterone and estrogen synthesis. Hormone synthesis is predominantly performed by members of the cytochrome P-450 (CYP) enzyme family including CYP11A1 or CYP19A1 and hydroxysteroid dehydrogenases (HSDs) such as 3β-HSD and 17β-HSD. Placental estrogen synthesis requires delivery of sulfate-conjugated precursor molecules from fetal and maternal serum. Placental uptake of these precursors is mediated by members of the solute carrier (SLC) family including sodium-dependent organic anion transporter (SOAT), organic anion transporter 4 (OAT4), and organic anion transporting polypeptide 2B1 (OATP2B1). Maternal–fetal glucocorticoid transport has to be tightly regulated in order to ensure healthy fetal growth and development. For that purpose, the placenta expresses the enzymes 11β-HSD 1 and 2 as well as the transporter ABCB1. This article also summarizes the impact of diverse compounds and diseases on the expression level and activity of the involved transporters, receptors, and metabolizing enzymes and concludes that the regulatory mechanisms changing the physiological to a pathophysiological state are barely explored. The structure and the cellular composition of the human placental barrier are introduced. While steroid production, metabolism and transport in the placental syncytiotrophoblast have been explored for decades, few information is available for the role of placental-fetal endothelial cells in these processes. With regard to placental structure and function, significant differences exist between species. To further decipher physiologic pathways and their pathologic alterations in placental steroid handling, proper model systems are mandatory.

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Section: Steroid Hormonesmentioning

confidence: 99%

Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta

2018

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“…Individual differences in emotional response to life events are thought to affect levels of inflammation indirectly through health behaviors, and/or directly through biological pathways. The HPA axis is one established biological pathway that activates in response to psychological distress and is important for mobilization of adaptive metabolic resources, including modulation of inflammatory processes (Castro, Elias, Elias, & Moreira, 2011; Schoneveld & Cidlowski, 2007; Tsigos & Chrousos, 2002). A meta-analytic review of over 50 years of human research concluded that persistent psychological distress is accompanied by dysregulation of cortisol hormone secretion, with higher than normal levels of cortisol secreted over the course of the day (G.…”

Section: Introductionmentioning

confidence: 99%

Development of glucocorticoid resistance over one year among mothers of children newly diagnosed with cancer

Walsh

Ewing

Cleary

et al. 2018

Brain, Behavior, and Immunity

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Chronic distress associates with peripheral release of cortisol and a parallel upregulation of innate inflammation. Typically, cortisol functions to down-regulate inflammatory processes. However, in the context of chronic stress, it is hypothesized that glucocorticoid receptors within immune cells become less sensitive to the anti-inflammatory effects of cortisol, resulting in increased systemic inflammation. Caring for a child newly diagnosed with cancer is a particularly provocative chronic stressor. Here, we examine evidence for the development of cellular resistance to glucocorticoids among 120 mothers (Aged 18-56 years; 86% Caucasian) across the 12 months following their child's new diagnosis with cancer. Measures of psychological distress, interleukin (IL)-6, and glucocorticoid resistance (GCR) were assessed 1, 6, and 12 months after the diagnosis. A latent factor for distress was derived from the covariation among symptoms of anxiety, depression, and post-traumatic stress. Latent change score models revealed a significant positive association between change in distress and change in GCR from 0 to 6 months, and 6 months-1 year. This finding provides initial evidence for a longitudinal association between change in maternal distress and change in GCR from the onset of a chronic stressor through one year. Although levels of IL-6 increased during the first six months after the child's diagnosis, the magnitude of this change was not related to change in distress or change in GCR. Given the possible health consequences of reduced immune sensitivity to glucocorticoids, future work should further explore this stress response and its clinical significance.

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“…Simply put, corticotrophin releasing hormone (CRH) activates the anterior pituitary to produce adrenocorticotrophic hormone (ACTH) which then activates the adrenal cortex to produce glucocorticoids. 66 Glucocorticoids can affect the function of various components of the innate and adaptive immune system through gene modulation. 67 Exogenous glucocorticoids can suppress cellular immunity, promote humoral immunity, and induce tolerance against certain antigens through the alteration of Tand B cell function.…”

Section: Opioids and Hypothalamic-pituitaryadrenal Axismentioning

confidence: 99%

Opioids and immune modulation: more questions than answers

Al-Hashimi

Scott

Thompson

et al. 2013

British Journal of Anaesthesia

168

146

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Opioid addicts are more likely to present with infections suggesting opioids are immune modulators. The potential sites/mechanism(s) for this modulation are controversial and on close inspection not well supported by the current literature. It has long been assumed that opioid-induced immune modulation occurs via a combination of direct actions on the immune cell itself, via the hypothalamic-pituitary-adrenal (HPA) axis, or both. Opioid receptors are classified as MOP (μ, mu), DOP (δ, delta), and KOP (κ, kappa)--classical naloxone sensitive receptors--or NOP (the receptor for nociceptin/orphanin FQ), which is naloxone insensitive. Opioids currently used in clinical practice predominantly target the MOP receptor. There do not appear to be classical opioid receptors present on immune cells. The evidence for HPA activation is also poor and shows some species dependence. Most opioids used clinically or as drugs of abuse do not target the NOP receptor. Other possible target sites for immune modulation include the sympathetic nervous system and central sites. We are currently unable to accurately define the cellular target for immune modulation and suggest further investigation is required. Based on the differences observed when comparing studies in laboratory animals and those performed in humans we suggest that further studies in the clinical setting are needed.

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Physiology and Pathophysiology of the HPA Axis

Cited by 12 publications

References 181 publications

Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta

Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta

Development of glucocorticoid resistance over one year among mothers of children newly diagnosed with cancer

Opioids and immune modulation: more questions than answers

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