title: Hippocampal and hypothalamic type I corticosteroid receptor affinities are reduced in adult rats born by a caesarean procedure with or without an added period of anoxia.
abstract: Brief periods of hypoxia during labour and birth are a frequent occurrence. Within the CNS, the hippocampus is known to be particularly vulnerable to the damaging effects of hypoxia/ischaemia in both adult and immature animals. The hippocampus also contains the highest concentration of corticosteroid receptors of any brain region and both mineralocorticoid (type I) receptors and glucocorticoid (type II) receptors in the hippocampus play a role in the regulation of basal diurnal and stress-induced glucocorticoid secretion. Given this background, the aim of this study was to test whether an acute period of anoxia during the birth process may have lasting effects on CNS corticosteroid receptor levels and/or pituitary-adrenocortical function. Type I and type II corticosteroid receptor binding sites in the hippocampus and hypothalamus were compared in adult rats that had been born vaginally, born by a Caesarean procedure or born by a Caesarean procedure with 5, 10 or 15 min of added anoxia. Using 14 nM [3H]corticosterone as radioligand, mineralocorticoid receptor binding was reduced by approximately 50% in the hippocampus and hypothalamus of adult rats that had been born by the Caesarean procedure either with or without an added period of anoxia, in comparison to vaginally born controls. Saturation analysis revealed that these reductions resulted from decreases in affinity of the mineralocorticoid receptor for [3H]corticosterone, with no change in numbers of receptors. Birth condition had no effect on glucocorticoid receptor binding capacities in the hippocampus or hypothalamus. A small increase in basal corticosterone secretion during the diurnal trough was observed in adult animals that had been born by Caesarean section with 5 or 15 min of added anoxia. The plasma corticosterone response to a 20-min restraint stress was reduced in adult animals born by Caesarean section with or without an added period of anoxia, in comparison to vaginally born controls. However the adrenocorticotropin response to stress was largely unaffected by birth condition. The results indicate that an acute birth insult is sufficient to produce long-lasting alterations in hippocampal and hypothalamic mineralocorticoid receptor sites, accompanied by changes in basal and stress-induced glucocorticoid secretion.
authors.affiliation: Douglas Hospital Research Centre, Department of Psychiatry, McGill University, Montreal, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Boksa
authors.forename: A
authors.initials: A
authors.lastname: Krishnamurthy
authors.forename: S
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D036861:Delivery, Obstetric; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D000860:Hypoxia / Q000503:physiopathology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011987:Receptors, Steroid / Q000378:metabolism*
chemical_list: D011987:Receptors, Steroid; D000324:Adrenocorticotropic Hormone