Maternal prenatal licorice consumption alters hypothalamic–pituitary–adrenocortical axis function in children

Räikkönen, Katri; Seckl, Jonathan R.; Heinonen, Kati; Pyhälä, Riikka; Feldt, Kimmo; Jones, Alexander; Pesonen, Anu‐Katriina; Phillips, David I. W.; Lahti, Jari; Järvenpää, Anna‐Liisa; Eriksson, Johan G.; Matthews, Karen A.; Strandberg, Timo; Kajantie, Eero

doi:10.1016/j.psyneuen.2010.04.010

Cited by 87 publications

(52 citation statements)

References 20 publications

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“…Furthermore, exposure to glycyrrhizin at these levels also altered diurnal and stress-induced hypothalamic-pituitary-adrenocortical axis function at the age of 8.1 years in a dose-associated manner (Räikkönen et al, 2009(Räikkönen et al, , 2010.…”

Section: Pregnancymentioning

confidence: 99%

Pharmacological Effects ofGlycyrrhizaspp. and Its Bioactive Constituents: Update and Review

2015

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The roots and rhizomes of various species of the perennial herb licorice (Glycyrrhiza) are used in traditional medicine for the treatment of several diseases. In experimental and clinical studies, licorice has been shown to have several pharmacological properties including antiinflammatory, antiviral, antimicrobial, antioxidative, antidiabetic, antiasthma, and anticancer activities as well as immunomodulatory, gastroprotective, hepatoprotective, neuroprotective, and cardioprotective effects. In recent years, several of the biochemical, molecular, and cellular mechanisms of licorice and its active components have also been demonstrated in experimental studies. In this review, we summarized the new phytochemical, pharmacological, and toxicological data from recent experimental and clinical studies of licorice and its bioactive constituents after our previous published review.

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Section: Pregnancymentioning

confidence: 99%

Pharmacological Effects ofGlycyrrhizaspp. and Its Bioactive Constituents: Update and Review

2015

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“…Similarly, 11␤-HSD2 knockout mice have decreased weight at birth (288). Furthermore, Finnish women who voluntarily eat larger amounts of licorice-containing foodstuffs in pregnancy have shorter gestations and their children show poorer cognitive function and behavioral disturbances (increases in attention seeking, rule breaking, and aggression) coupled with hyperactivity of their HPA axis (569,570). Licorice directly inhibits human placental 11␤-HSD2 immediately ex vivo (66), increasing passage of cortisol to the fetal circulation.…”

Section: Chapman Holmes and Secklmentioning

confidence: 99%

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Chapman

Holmes

Seckl

2013

Physiological Reviews

735

601

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Glucocorticoid action on target tissues is determined by the density of “nuclear” receptors and intracellular metabolism by the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) which catalyze interconversion of active cortisol and corticosterone with inert cortisone and 11-dehydrocorticosterone. 11β-HSD type 1, a predominant reductase in most intact cells, catalyzes the regeneration of active glucocorticoids, thus amplifying cellular action. 11β-HSD1 is widely expressed in liver, adipose tissue, muscle, pancreatic islets, adult brain, inflammatory cells, and gonads. 11β-HSD1 is selectively elevated in adipose tissue in obesity where it contributes to metabolic complications. Similarly, 11β-HSD1 is elevated in the ageing brain where it exacerbates glucocorticoid-associated cognitive decline. Deficiency or selective inhibition of 11β-HSD1 improves multiple metabolic syndrome parameters in rodent models and human clinical trials and similarly improves cognitive function with ageing. The efficacy of inhibitors in human therapy remains unclear. 11β-HSD2 is a high-affinity dehydrogenase that inactivates glucocorticoids. In the distal nephron, 11β-HSD2 ensures that only aldosterone is an agonist at mineralocorticoid receptors (MR). 11β-HSD2 inhibition or genetic deficiency causes apparent mineralocorticoid excess and hypertension due to inappropriate glucocorticoid activation of renal MR. The placenta and fetus also highly express 11β-HSD2 which, by inactivating glucocorticoids, prevents premature maturation of fetal tissues and consequent developmental “programming.” The role of 11β-HSD2 as a marker of programming is being explored. The 11β-HSDs thus illuminate the emerging biology of intracrine control, afford important insights into human pathogenesis, and offer new tissue-restricted therapeutic avenues.

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“…Regulation of cortisol exposure through activity of HSD11B2 appears critical as the offspring of women who consumed large quantities of liquorice had significantly impaired cognitive and behavioural development [111,112] . A recent study has attempted to dissect the mechanisms underlying the altered infant neurodevelopment showing higher maternal cortisol levels measured in earlier but not later gestation were associated with a larger right amygdala volume measured by MRI in girls at age 7 years [113] .…”

Section: Maternal Hpa Axis and Offspring Outcomesmentioning

confidence: 99%

Changes in the Maternal Hypothalamic-Pituitary-Adrenal Axis in Pregnancy and Postpartum: Influences on Maternal and Fetal Outcomes

Duthie¹,

Reynolds²

2013

Neuroendocrinology

274

221

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Overexposure of the developing fetus to glucocorticoids is hypothesised to be one of the key mechanisms linking early life development with later life disease. The maternal hypothalamic-pituitary-adrenal (HPA) axis undergoes dramatic changes during pregnancy and postpartum. Although cortisol levels rise threefold by the third trimester, the fetus is partially protected from high cortisol by activity of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2). Maternal HPA axis activity and activity of HSD11B2 may be modified by maternal stress and disease allowing greater transfer of glucocorticoids from mother to fetus. Here we review emerging data from human studies linking dysregulation of the maternal HPA axis to outcomes in both the mother and her offspring. For the offspring, greater glucocorticoid exposure is associated with lower birth weight and shorter gestation at delivery. In addition, evidence supports longer term consequences for the offspring including re-setting of the HPA axis and susceptibility to neurodevelopmental problems and cardiometabolic disease. For the mother, the changes in the HPA axis, particularly in the postpartum period, may increase vulnerability to mood disturbances. Further understanding of the changes in the HPA axis during pregnancy and the impact of these changes may ultimately allow early identification of those most at risk of future disease.

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Maternal prenatal licorice consumption alters hypothalamic–pituitary–adrenocortical axis function in children

Cited by 87 publications

References 20 publications

Pharmacological Effects ofGlycyrrhizaspp. and Its Bioactive Constituents: Update and Review

Pharmacological Effects ofGlycyrrhizaspp. and Its Bioactive Constituents: Update and Review

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Changes in the Maternal Hypothalamic-Pituitary-Adrenal Axis in Pregnancy and Postpartum: Influences on Maternal and Fetal Outcomes

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