Ontogeny of steroid receptor coactivators in the hippocampus and their role in regulating postnatal HPA axis function.
The function and regulation of the hypothalamic-pituitary-adrenal (HPA) axis during ontogeny differs markedly from the situation in adult animals. Postnatally mice undergo a so-called stress hypo-responsive period, which is characterized by a relative inability of mild stressors to induce a marked corticosterone response. Steroid receptor coactivators (SRCs) have been shown to influence the function of the HPA axis in adult animals by interacting with steroid receptors as the mineralocorticoid and the glucocorticoid receptor. Here we test the hypothesis that expression changes of the three identified SRC genes (SRC1, SRC2 and SRC3) correlate with differences in HPA axis activity during postnatal development. First, we mapped the ontogeny of the three SRCs during postnatal development in the hippocampus. We found a time- and region-specific regulation of gene expression, which was specific for each SRC. However, there was no relation between the age-dependent stress system activity and the expression levels of the SRCs. Further, we studied the acute regulation of the three SRCs following maternal deprivation in 9-day-old wild-type or CRH receptor type 1 (CRHr1) knockout mice. Under these conditions, no differential expression of any of the tested SRCs could be detected. Thus, while it seems likely that their varying abundance throughout postnatal life affects steroid receptor function in the different hippocampal subregions, acute changes of HPA axis activity or reactivity are not mediated by hippocampal changes in expression of this coactivator family.
Schmidt
Mathias V
MV
Leiden-Amsterdam Center for Drug Research/Leiden University Medical Center, Leiden University, The Netherlands. mschmidt@mpipsykl.mpg.de
Oitzl
Melly
M
Steenbergen
Peter
P
Lachize
Servane
S
Wurst
Wolfgang
W
Müller
Marianne B
MB
de Kloet
E Ronald
ER
Meijer
Onno C
OC
D000818:Animals; D000831:Animals, Newborn; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000502:physiology*; D051548:Histone Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics* / Q000378:metabolism; D056921:Nuclear Receptor Coactivator 3; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011247:Pregnancy; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
C498002:Ncoa2 protein, mouse; D051958:Nuclear Receptor Coactivator 2; D015534:Trans-Activators; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C538861:Ncoa1 protein, mouse; C538867:Ncoa3 protein, mouse; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3