Antenatal Treatment with Glucocorticoids and the Hypotalamic-Pituitary-Adrenal Axis

Abstract

SummaryFetal development is a critical period in the life cycle which is why the placenta provides a structural and physiological barrier that protects the fetus from the outer fluctuations and inner disturbances. A variety of influences from the environment, however, might induce fetal overexposure to glucocorticoids that target the fetal hypothalamic-pituitaryadrenal (HPA) axis and influence the fetal growth trajectory. Development of the HPA axis starts in the early stages of pregnancy, but the timing of HPA axis maturation and the glucocorticoid receptor (GR) expression in relation to birth is highly species-specific. The functional state of the fetal HPA axis plays a key role in the maturation of many organs necessary for intrauterine development and existence after birth. A functional HPA axis in near-term fetuses provides an adequate response to stress and also affects the timing of parturition. Due to their potent effect on the maturation of fetal tissues, synthetic glucocorticoids are used in human pregnancy at risk of preterm delivery. Dexamethasone and betamethasone, as the ones most commonly used, cross the placental enzymatic barrier (11b-hydroxysteroid dehydrogenase type 2 -11b-HSD2) and have 25-fold higher affinity to the GR than endogenous glucocorticoids, stimulating many aspects of fetal maturation. Despite the numerous positive effects, exposure to synthetic glucocorticoids during fetal development may result in intrauterine growth retardation and fetal programming of the HPA axis function which is associated with cardiovascular, metabolic and psychiatric disorders manifested later in life. Long-term consequences indicate the need for the implementation of new studies that will pro- Kratak sadr`ajFetalni razvoj predstavlja kriti~an period tokom `ivotnog ci klusa, zbog ~ega placenta obezbe|uje strukturnu i fiziolo{ku barijeru koja {titi fetus od spolja{njih kolebanja i unutra{njih poreme}aja. Brojni uticaji iz okru`enja mogu dovesti do izlaganja fetusa povi{enoj koncentraciji glukokor tikoida koji deluju na fetalnu hipotalamo-hipofiznoadrenalnu (HPA) oso vinu i uti~u na rast. Razvoj HPA osovine po~inje veoma rano tokom gestacije, ali vreme njenog sazrevanja i ekspresije glukokortikoidnog receptora (GR) u odnosu na ro|enje je specifi~no za svaku vrstu. Fetalna HPA osovina ima klju~nu ulogu u sazrevanju brojnih organa tokom intrauterinog raz voja neophodnih za pre`ivljavanje nakon ro|enja, obezbe |uje adekvatan odgovor fetusa na stres, a uti~e i na vreme poro|aja. Usled sna`nog uticaja na sazrevanje fetalnih tkiva, sintetski glukokortikoidi se upotrebljavaju tokom rizi~nih trudno}a kod kojih postoji opasnost od prevremenog poro|aja. Deksametazon i betametazon, kao naj~e{}e kori{}eni lekovi u antenatalnoj terapiji, prolaze enzimsku placentalnu barijeru (11b-hidroksisteroid dehidrogenaza tip 2 -11b-HSD2) i imaju 25 puta ve}i afinitet vezivanja za GR u odnosu na endogene gluko kortikoide, stimuli{u}i mnoge procese sazrevanja fetusa. Uprkos brojnim pozitivnim efektima, izlaganje sintetskim glukokorti...

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