Genetic analysis of the stress-responsive adrenocortical axis

Leah C. Solberg, Amber E. Baum, Nasim Ahmadiyeh, Kazuhiro Shimomura, Renhua Li, Fred W. Turek, Joseph S. Takahashi, Gary A. Churchill, Eva E. Redei

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)362-369
Number of pages8
JournalPhysiological Genomics
Volume27
Issue number3
DOIs
StatePublished - Nov 27 2006

Fingerprint

Corticosterone
Quantitative Trait Loci
Globulins
Weights and Measures
Inbred Strains Rats
Phenotype
Genetic Loci
Sex Characteristics
Nucleotides
Genome
Genes

Keywords

  • Corticosterone
  • Hypothalamic-pituitary-adrenal axis
  • Quantitative trait loci analysis
  • Wistar Kyoto rat

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Solberg, L. C., Baum, A. E., Ahmadiyeh, N., Shimomura, K., Li, R., Turek, F. W., ... Redei, E. E. (2006). Genetic analysis of the stress-responsive adrenocortical axis. Physiological Genomics, 27(3), 362-369. https://doi.org/10.1152/physiolgenomics.00052.2006

Genetic analysis of the stress-responsive adrenocortical axis. / Solberg, Leah C.; Baum, Amber E.; Ahmadiyeh, Nasim; Shimomura, Kazuhiro; Li, Renhua; Turek, Fred W.; Takahashi, Joseph S.; Churchill, Gary A.; Redei, Eva E.

In: Physiological Genomics, Vol. 27, No. 3, 27.11.2006, p. 362-369.

Research output: Contribution to journalArticle

Solberg, LC, Baum, AE, Ahmadiyeh, N, Shimomura, K, Li, R, Turek, FW, Takahashi, JS, Churchill, GA & Redei, EE 2006, 'Genetic analysis of the stress-responsive adrenocortical axis', Physiological Genomics, vol. 27, no. 3, pp. 362-369. https://doi.org/10.1152/physiolgenomics.00052.2006
Solberg LC, Baum AE, Ahmadiyeh N, Shimomura K, Li R, Turek FW et al. Genetic analysis of the stress-responsive adrenocortical axis. Physiological Genomics. 2006 Nov 27;27(3):362-369. https://doi.org/10.1152/physiolgenomics.00052.2006
Solberg, Leah C. ; Baum, Amber E. ; Ahmadiyeh, Nasim ; Shimomura, Kazuhiro ; Li, Renhua ; Turek, Fred W. ; Takahashi, Joseph S. ; Churchill, Gary A. ; Redei, Eva E. / Genetic analysis of the stress-responsive adrenocortical axis. In: Physiological Genomics. 2006 ; Vol. 27, No. 3. pp. 362-369.
@article{6ea2d27858244d2da0766f188fe27987,
title = "Genetic analysis of the stress-responsive adrenocortical axis",
abstract = "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.",
keywords = "Corticosterone, Hypothalamic-pituitary-adrenal axis, Quantitative trait loci analysis, Wistar Kyoto rat",
author = "Solberg, {Leah C.} and Baum, {Amber E.} and Nasim Ahmadiyeh and Kazuhiro Shimomura and Renhua Li and Turek, {Fred W.} and Takahashi, {Joseph S.} and Churchill, {Gary A.} and Redei, {Eva E.}",
year = "2006",
month = "11",
day = "27",
doi = "10.1152/physiolgenomics.00052.2006",
language = "English (US)",
volume = "27",
pages = "362--369",
journal = "Physiological Genomics",
issn = "1531-2267",
publisher = "American Physiological Society",
number = "3",

}

TY - JOUR

T1 - Genetic analysis of the stress-responsive adrenocortical axis

AU - Solberg, Leah C.

AU - Baum, Amber E.

AU - Ahmadiyeh, Nasim

AU - Shimomura, Kazuhiro

AU - Li, Renhua

AU - Turek, Fred W.

AU - Takahashi, Joseph S.

AU - Churchill, Gary A.

AU - Redei, Eva E.

PY - 2006/11/27

Y1 - 2006/11/27

N2 - 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.

AB - 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.

KW - Corticosterone

KW - Hypothalamic-pituitary-adrenal axis

KW - Quantitative trait loci analysis

KW - Wistar Kyoto rat

UR - http://www.scopus.com/inward/record.url?scp=34248145937&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34248145937&partnerID=8YFLogxK

U2 - 10.1152/physiolgenomics.00052.2006

DO - 10.1152/physiolgenomics.00052.2006

M3 - Article

C2 - 16895972

AN - SCOPUS:34248145937

VL - 27

SP - 362

EP - 369

JO - Physiological Genomics

JF - Physiological Genomics

SN - 1531-2267

IS - 3

ER -