Maternal-fetal glucocorticoid milieu programs hypothalamic-pituitary-thyroid function of adult offspring.
To assess the role of maternal glucocorticoid milieu on the hypothalamic-pituitary-thyroid function of the offspring, we adrenalectomized (ADX) pregnant dams on gestation d 8 and implanted a placebo pellet or a continuous release 50- or 75-mg corticosterone (CORT) pellet. Maternal ADX led to realignment of the balance between maternal and fetal plasma CORT levels, resulting in an increase in CORT of fetal origin in the maternal compartment. Maternal ADX and low levels of CORT replacement had no discernable effect on maternal pituitary-thyroid measures. In contrast, the increase in fetal CORT, as a consequence of the absence of maternal glucocorticoids, decreased birth weight in neonates, decreased adult hypothalamic TRH mRNA levels, and increased plasma TSH levels in both male and female adult offspring, all of which were reversed by administration of basal levels of CORT to the pregnant ADX dam. Decreased plasma T3 concentrations in female offspring were reversed by administration of the higher levels of CORT to the ADX dams. Our data indicate that maternal glucocorticoids modulate the developing hypothalamic-pituitary-thyroid axis.
Slone-Wilcoxon
Jennifer
J
303 East Chicago Avenue, Ward 9-198, Chicago, Illinois 60611, USA.
Redei
Eva E
EE
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000367:Age Factors; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology*; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000196:embryology / Q000502:physiology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000196:embryology / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000187:drug effects / Q000196:embryology / Q000502:physiology*; D013972:Thyrotropin / Q000097:blood / Q000235:genetics; D014284:Triiodothyronine / Q000097:blood
D000893:Anti-Inflammatory Agents; D012333:RNA, Messenger; D014284:Triiodothyronine; D000324:Adrenocorticotropic Hormone; D013972:Thyrotropin; D003345:Corticosterone