Long-term effects of neonatal maternal deprivation and ACTH on hippocampal mineralocorticoid and glucocorticoid receptors.
In the brain, corticosteroids bind to two types of receptors, the classical glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). The effects of different manipulations taking place during early ontogeny on GR and MR binding properties were examined in the adult hippocampus. Infant rats at postnatal day (pnd) 3 were deprived of maternal contact for 24 h and injected with saline or ACTH1-24 at the end of the deprivation period. They were then returned to their dams and weaned on pnd 21. At pnd 48, they were sacrificed (24 h post adrenalectomy) and the hippocampal MR and GR measured using an in vitro cytosol binding assay. In the male rats, deprivation and deprivation + ACTH resulted in a reduction of GRs. MRs were also significantly down regulated in the deprived males. In the female rats, saline injections in deprived female rats resulted in increased GR capacity and ACTH injections led to a further up-regulation of the GRs. None of the early manipulations influenced the regulation of the MRs in females. The binding affinity for corticosteroid receptors was also altered by some of the early manipulations. These results in adult (7-week-old) rats indicate that the receptor systems for corticosteroids in the brain are sensitive to brief manipulations occurring early in development. These changes in receptor capacity and/or affinity may affect corticosteroid-mediated processes in the adult rat.
Sutanto
W
W
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Sylvius Laboratories, University of Leiden, The Netherlands.
Rosenfeld
P
P
de Kloet
E R
ER
Levine
S
S
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008426:Maternal Deprivation; D009473:Neuronal Plasticity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000378:metabolism*; D012727:Sex Characteristics; D015854:Up-Regulation / Q000187:drug effects
D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D000324:Adrenocorticotropic Hormone