1. Physiol Genomics. 2006 Nov 27;27(3):362-9. Epub 2006 Aug 8.
Genetic analysis of the stress-responsive adrenocortical axis.
Solberg LC(1), Baum AE, Ahmadiyeh N, Shimomura K, Li R, Turek FW, Takahashi JS,
Churchill GA, Redei EE.
Author information:
(1)Department of Psychiatry and Behavioral Science, Northwestern University
Feinberg School of Medicine, Chicago, USA.
The underlying genetic components contributing to individual variability in
functions of the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis are
poorly understood. To determine genetic loci mediating three aspects of the
adrenocortical function, we conducted a quantitative trait locus (QTL) analysis
in the segregating F2 generation of a Wistar Kyoto (WKY) x Fischer 344 (F344)
cross, two inbred rat strains that differ in several HPA axis measures. The
following three components of adrenocortical function are known to be regulated
by different mechanisms that are mediated via suprahypothalamic, hypothalamic,
pituitary, and intra-adrenal influences: basal plasma corticosterone (Cort)
levels, plasma Cort response to a 10-min restraint stress, and adrenal weight.
Genome scans identified a complex genetic architecture for the basal Cort
phenotype, including sex and maternal lineage effects. Pairwise interactions were
also identified for this trait. We identified three significant and two
suggestive QTLs for stress Cort, along with two pairs of interacting loci for
this trait. Four highly significant and two suggestive loci were identified for
adrenal weight, with no interacting loci. In contrast to basal Cort, no sex- or
lineage-dependent QTL were identified for stress Cort or adrenal weight, despite
the large sex differences in these phenotypes. We identified three nucleotide
alterations in an obvious candidate gene mapped to the most significant QTL for
stress Cort, Cort-binding globulin (CBG), one of which is known to alter CBG
binding. This analysis confirms that three separate traits regulated by the HPA
axis are controlled by multiple, but mainly nonoverlapping, QTLs.
PMID: 16895972 [PubMed - indexed for MEDLINE]
PUBMED: 16895972
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