Interaction between Dax-1 and steroidogenic factor-1 in vivo: increased adrenal responsiveness to ACTH in the absence of Dax-1

Endocrinology. 2002 Feb;143(2):665-73. doi: 10.1210/endo.143.2.8658.


Two nuclear receptors, dosage-sensitive sex reversal adrenal hypoplasia congenita, critical region on the X chromosome gene-1 (Dax-1) and steroidogenic factor-1 (SF-1), are required for adrenal development and function. In vitro assays suggest that Dax-1 represses SF-1 mediated transcription. In this study, we generated SF-1(+/-): Dax-1(-/Y) mice to examine the role of Dax-1 in SF-1-dependent steroidogenesis in vivo. While the SF-1 expression was impaired in SF-1(+/-) mice, there was no change in Dax-1 expression in SF-1(+/-) mice and no change in SF-1 expression in Dax-1(-/Y) mice. SF-1(+/-) mice had small adrenal glands with adrenal hypoplasia and cellular hypertrophy. The loss of Dax-1 in SF-1(+/-): Dax-1(-/Y) mice reversed the decreased adrenal weight and histological abnormalities observed in SF-1(+/-) mice. SF-1(+/-) mice had elevated ACTH and the lowest corticosterone following restraint stress. In contrast, Dax-1(-/Y) mice had elevated corticosterone and decreased ACTH. Adrenal responsiveness (ACTH/corticosterone) was highest in Dax-1(-/Y) mice, intermediate in WT and SF-1(+/-): Dax-1(-/Y) mice, and lowest in SF-1(+/-) mice. In accordance with these findings, ACTH stimulation testing resulted in the highest levels of corticosterone in the Dax-1(-/Y) mice. Protein levels of P450c21 and the ACTH receptor were increased in Dax-1(-/Y) mice and intermediate in SF-1(+/-): Dax-1(-/Y) mice following chronic food deprivation. These results are consistent with a model in which Dax-1 functions to inhibit SF-1-mediated steroidogenesis in vivo.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Cortex / metabolism
  • Adrenal Cortex / physiology
  • Adrenal Glands / growth & development
  • Adrenal Glands / physiology*
  • Adrenocorticotropic Hormone / blood
  • Adrenocorticotropic Hormone / physiology*
  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Corticosterone / blood
  • DAX-1 Orphan Nuclear Receptor
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology*
  • Female
  • Food Deprivation / physiology
  • Fushi Tarazu Transcription Factors
  • Homeodomain Proteins
  • Male
  • Mice
  • Mice, Inbred DBA
  • Mice, Knockout
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid / biosynthesis
  • Receptors, Retinoic Acid / genetics*
  • Receptors, Retinoic Acid / physiology*
  • Repressor Proteins*
  • Restraint, Physical
  • Steroidogenic Factor 1
  • Stress, Psychological / physiopathology
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • Transcription Factors / physiology*
  • Transcription, Genetic / genetics


  • DAX-1 Orphan Nuclear Receptor
  • DNA-Binding Proteins
  • Fushi Tarazu Transcription Factors
  • Homeodomain Proteins
  • Nr0b1 protein, mouse
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid
  • Repressor Proteins
  • Steroidogenic Factor 1
  • Transcription Factors
  • steroidogenic factor 1, mouse
  • Adrenocorticotropic Hormone
  • Corticosterone