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.
Department of Psychology, University of Helsinki, P.O. Box 9 (Siltavuorenpenger 20 D), 00014 University of Helsinki, Finland. katri.raikkonen@helsinki.fi
Katri
K
Räikkönen
Jonathan R
JR
Seckl
Kati
K
Heinonen
Riikka
R
Pyhälä
Kimmo
K
Feldt
Alexander
A
Jones
Anu-Katriina
AK
Pesonen
David I W
DI
Phillips
Jari
J
Lahti
Anna-Liisa
AL
Järvenpää
Johan G
JG
Eriksson
Karen A
KA
Matthews
Timo E
TE
Strandberg
Eero
E
Kajantie
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