The pituitary-adrenal axis of fetal rats after maternal dexamethasone treatment.
Elevated glucocorticoid level in the gravid female circulation affects number of endocrine functions in fetuses and offspring. In this research female rats were injected with dexamethasone (Dx) in three consecutive daily doses of 1.0, 0.5, 0.5 mg/kg body weight, starting from day 16 of pregnancy. The influence of this treatment on the pituitary adrenocorticotrophic (ACTH) cells and adrenal glands of 19-day-old fetuses was examined immunocytochemically and by morphometric analysis. Moreover, the proliferative activity of adrenocortical cells was estimated after application of the mitotic inhibitor Oncovine. Administration of Dx to pregnant rats induced a decline of fetal ACTH cell immunopositivity and significant decreases of ACTH cell volume (23%, p < 0.05), volume density (41%, p < 0.05), and its number per unit area (17%, p < 0.05) in comparison to the control 19-day-old fetuses. Reduced proliferative activity of adrenocortical cells (31%; p < 0.05) in zona glomerulosa, as well as the volume of this zone were detected. The volume and number of fetal adrenocortical cells in the inner zone and chromoblasts were not significantly reduced after Dx treatment of pregnant rats. These results show that maternal Dx administration in the period when the fetal hypothalamo-pituitary-adrenal (PA) axis begins its function inhibited the PA axis. Reduced ACTH cell function and mitotic activity led to suppression of adrenocortical cell multiplication in zona glomerulosa, the region of the adrenal cortex where most proliferating cells were found in control 19-day-old fetuses. Thus, increased glucocorticoid levels during late pregnancy caused developmental modifications involving the fetal PA axis, which could be the basis of the altered endocrine responsiveness in adult life.
Stojanoski
Milica Manojlović
MM
Institute for Biological Research, Sinisa Stanković, 29 Novembra 142, 11060, Belgrade, Serbia and Montenegro. manojlo@ibiss.bg.ac.yu
Nestorović
Natasa
N
Negić
Natasa
N
Filipović
Branko
B
Sosić-Jurjević
Branka
B
Milosević
Verica
V
Sekulić
Milka
M
D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008297:Male; D010913:Pituitary-Adrenal System / Q000166:cytology / Q000187:drug effects* / Q000196:embryology* / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D006131:Growth Inhibitors; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone