Abstract
Progesterone metabolites acting via GABAA receptors suppress central nervous system (CNS) activity. The aim of the present study was to examine binding characteristics of GABAA receptors in fetal, newborn and adult sheep brains using [35S]TBPS, and to determine the effects of allopregnanolone on this binding. Receptor affinity (KD) and density (BMAX) in the brainstem were not different in fetal, newborn (1–2 days old) and adult brains. In the hypothalamus KD and BMAX increased significantly in the fetus between 85 and 128 days gestation, and were then similar to postnatal and adult values. In the frontal cortex KD and BMAX increased progressively between 85 days and term (∼147 days gestation), and were then not different from postnatal and adult values. The Ki values for the GABAA receptor antagonist picrotoxin was similar at all ages. Allopregnanolone inhibited [35S]TBPS binding in the presence of 5 μM GABA, but enhanced binding in the absence of GABA. These results show that (i), functional GABAA receptors are present in the fetal brain from at least 85 days gestation; (ii), 3α-pregnane steroids modify receptor affinity in the late gestation fetal brain; and (iii) there are region-specific changes in GABAA receptor binding parameters. Steroid modulation of the GABAA receptor in the fetal brain is likely to influence fetal CNS activity in late gestation.
Published Version
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