A naturally hypersensitive glucocorticoid receptor elicits a compensatory reduction of hypothalamus-pituitary-adrenal axis activity early in ontogeny.

Repeated measures analysis across all four sampling time points confirmed an overall trend of the GR Ala610Val substitution to reduce plasma cortisol (genotype p < 0.001; electronic supplementary material, table S1) and ACTH levels (genotype p = 0.001; electronic supplementary material, table S1), which were approximately 40–50% lower in homozygous carriers of the Val variant compared with wild-type littermates. 2.3.

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The results revealed a similar marked, highly significant reduction in size of the adrenal cortex associated with the Val variant (genotype p < 0.001; figure 3 b ; electronic supplementary material, table S1), but only a slight and insignificant reduction in the size of the adrenal medulla (genotype p = 0.639; figure 3 c ; electronic supplementary material, table S1).

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Carriers of the Val variant also displayed lower ACTH levels compared with wild-type animals 1 day after weaning, but this difference did not reach statistical significance (genotype p = 0.111; figure 2 c ; electronic supplementary material, table S1).

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