Maternal prenatal licorice consumption alters hypothalamic-pituitary-adrenocortical axis function in children.
Overexposure to glucocorticoids has been proposed as a mechanism by which prenatal adversity 'programs' the function of the hypothalamic-pituitary-adrenocortical axis (HPAA), thereby increasing the risk of adult diseases. Glycyrrhizin, a natural constituent of licorice, potently inhibits 11β-hydroxysteroid dehydrogenase type 2, the feto-placental barrier to the higher maternal cortisol levels. We studied if maternal consumption of glycyrrhizin in licorice associates with HPAA function in children. Diurnal salivary cortisol and salivary cortisol during the Trier Social Stress Test for Children (TSST-C) were measured in children (n=321, mean age=8.1, SD=0.3 years) whose mothers consumed varying levels of glycyrrhizin in licorice during pregnancy; exposure-level groups were labeled high (≥500 mg/week), moderate (250-499 mg/week) and zero-low (0-249 mg/week). In comparison to the zero-low exposure group, children in the high exposure group had 19.2% higher salivary cortisol awakening peak, 33.1% higher salivary cortisol awakening slope, 15.4% higher salivary cortisol awakening area under the curve (AUC), 30.8% higher baseline TSST-C salivary cortisol levels, and their salivary cortisol levels remained high throughout the TSST-C protocol (P-values <0.05). These effects appeared dose-related. Our findings lend support to prenatal 'programming' of HPAA function by overexposure to glucocorticoids.
Räikkönen
Katri
K
Department of Psychology, University of Helsinki, P.O. Box 9 (Siltavuorenpenger 20 D), 00014 University of Helsinki, Finland. katri.raikkonen@helsinki.fi
Seckl
Jonathan R
JR
Heinonen
Kati
K
Pyhälä
Riikka
R
Feldt
Kimmo
K
Jones
Alexander
A
Pesonen
Anu-Katriina
AK
Phillips
David I W
DI
Lahti
Jari
J
Järvenpää
Anna-Liisa
AL
Eriksson
Johan G
JG
Matthews
Karen A
KA
Strandberg
Timo E
TE
Kajantie
Eero
E
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000037:antagonists & inhibitors; D000328:Adult; D019540:Area Under Curve; D002648:Child; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006035:Glycyrrhiza; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D012463:Saliva / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism
D019695:Glycyrrhizic Acid; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D006854:Hydrocortisone