Endocrine regulation of HOX genes

Endocr Rev. 2006 Jun;27(4):331-55. doi: 10.1210/er.2005-0018. Epub 2006 Apr 21.


Hox genes have a well-characterized role in embryonic development, where they determine identity along the anteroposterior body axis. Hox genes are expressed not only during embryogenesis but also in the adult, where they are necessary for functional differentiation. Despite the known function of these genes as transcription factors, few regulatory mechanisms that drive Hox expression are known. Recently, several hormones and their cognate receptors have been shown to regulate Hox gene expression and thereby mediate development in the embryo as well as functional differentiation in the adult organism. Estradiol, progesterone, testosterone, retinoic acid, and vitamin D have been shown to regulate Hox gene expression. In the embryo, the endocrine system directs axial Hox gene expression; aberrant Hox gene expression due to exposure to endocrine disruptors contributes to the teratogenicity of these compounds. In the adult, endocrine regulation of Hox genes is necessary to enable such diverse functions as hematopoiesis and reproduction; endocrinopathies can result in dysregulated HOX gene expression affecting physiology. By regulating HOX genes, hormonal signals utilize a conserved mechanism that allows generation of structural and functional diversity in both developing and adult tissues. This review discusses endocrine Hox regulation and its impact on physiology and human pathology.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Benzhydryl Compounds
  • Diethylstilbestrol / adverse effects
  • Endometrium / metabolism
  • Female
  • Gene Expression Regulation, Developmental*
  • Genes, Homeobox*
  • Gonadal Steroid Hormones / physiology*
  • Hematopoiesis / physiology
  • Homeobox A10 Proteins
  • Homeodomain Proteins / metabolism
  • Humans
  • Insulin-Like Growth Factor Binding Protein 1 / metabolism
  • Integrin beta3 / metabolism
  • Methoxychlor / toxicity
  • Phenols / toxicity
  • Phytoestrogens / adverse effects
  • Pregnancy / metabolism
  • Receptors, Prostaglandin E / metabolism
  • Transcription Factors
  • Tretinoin / physiology
  • Vitamin D / physiology


  • Benzhydryl Compounds
  • Gonadal Steroid Hormones
  • Homeobox A10 Proteins
  • Homeodomain Proteins
  • Insulin-Like Growth Factor Binding Protein 1
  • Integrin beta3
  • Phenols
  • Phytoestrogens
  • Receptors, Prostaglandin E
  • Transcription Factors
  • empty spiracles homeobox proteins
  • HOXA10 protein, human
  • Vitamin D
  • Tretinoin
  • Diethylstilbestrol
  • bisphenol A
  • Methoxychlor