Sim2 contributes to neuroendocrine hormone gene expression in the anterior hypothalamus

Mol Endocrinol. 2004 May;18(5):1251-62. doi: 10.1210/me.2003-0372. Epub 2004 Feb 26.


Paraventricular (PVN) and supraoptic nuclei of the hypothalamus maintain homeostasis by modulating pituitary hormonal output. PVN and supraoptic nuclei contain five major cell types: oxytocin-, vasopressin-, CRH-, somatostatin-, and TRH-secreting neurons. Sim1, Arnt2, and Otp genes are essential for terminal differentiation of these neurons. One of their common downstream genes, Brn2, is necessary for oxytocin, vasopressin, and CRH cell differentiation. Here we show that Sim2, a paralog of Sim1, contributes to the expression of Trh and Ss genes in the dorsal preoptic area, anterior-periventricular nucleus, and PVN. Sim2 expression overlaps with Trh- and Ss-expressing cells, and Sim2 mutants contain reduced numbers of Trh and Ss cells. Genetically, Sim1 acts upstream of Sim2 and partially compensates for the loss of Sim2. Comparative expression studies at the anterior hypothalamus at early stages reveal that there are separate pools of Trh cells with distinctive molecular codes defined by Sim1 and Sim2 expression. Together with previous reports, our results demonstrate that Sim1 and Otp utilize two common downstream genes, Brn2 and Sim2, to mediate distinctive sets of neuroendocrine hormone gene expression.

Publication types

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

MeSH terms

  • Animals
  • Anterior Hypothalamic Nucleus / metabolism*
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation / physiology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation / physiology*
  • Mice
  • Mice, Mutant Strains
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • Oxytocin / metabolism
  • POU Domain Factors
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Preoptic Area / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Somatostatin / metabolism
  • Supraoptic Nucleus / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Vasopressins / metabolism


  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Nerve Tissue Proteins
  • POU Domain Factors
  • Repressor Proteins
  • Sim1 protein, mouse
  • Sim2 protein, mouse
  • Transcription Factors
  • Vasopressins
  • Pou3f2 protein, mouse
  • Oxytocin
  • Somatostatin