Effect of maternal administration of the antiestrogen ethamoxy triphetol throughout the last third of baboon gestation upon neonatal corticoid production

Abstract

The present study determined in baboon neonates whether corticoid production, which is markedly different in preterm baboon neonates, newborns and adult baboons is regulated by estrogen, and therefore, altered by maternal administration of the antiestrogen ethamoxytriphetol (MER-25) throughout the final third of baboon gestation. The metabolic clearance rate (MCR), transfer constant (ρ), production (PR) and secretion (SR) rates of cortisol (F) and cortisone (E) were determined by continuous infusion of [3H] F and[14C]E in baboon neonates delivered spontaneously to untreated mothers and to mothers, which had received MER-25 p.o. (15 mg/kg BW) daily throughout the final third of baboon gestation.MCR-E exceeded (P < 0.05) MCR-F in both groups. The ρ F→E was greater than ρ E→F in neonates of untreated (3.5 fold, P < 0.005) and MER-25-treated (1.8 fold, P < 0.025) mothers. Mean (±SE) ρ F→E was lower (P < 0.01) in neonates delivered to mothers, which had received antiestrogen (29.2±4.4%) than in untreated mothers (59.7±8.9%). Mean (±SE) conversion ratio of F→E (F→E — E→F) was lower (P < 0.05) in neonates of antiestrogen-treated (13.7±5.5) than of untreated (41.9±10.9) mothers. Since ρ is the proportion of blood PR of precursor converted to product (i.e. F to E) it is evident that neonatal F and E production in baboons are influenced by maternal administration of antiestrogen. Thus, mean (±SE) PR-E was greater (P < 0.05) than PR-F in controls (6.79±1.23 (E), 3.69± 0.55 (F) μg/min/kg BW), but not in neonates of antiestrogen-treated mothers (4.51±1.12 (E), 3.56±0.98 (F) μg/min/kg BW).Assuming that MER-25 interfered with the action of estrogen in the fetus, our results suggest that estrogen, which is produced in increasing amounts into the maternal and fetal circulation with advancing baboon gestation, regulates the pattern of baboon fetal corticosteroidogenesis, a pattern which is distinct from that in newborns and adults and presumably represents maturational events leading to extrauterine self sufficiency.