Transient dwarfism and hypogonadism in mice lacking Otx1 reveal prepubescent stage-specific control of pituitary levels of GH, FSH and LH

Dario Acampora, Sylvie Mazan, Francesca Tuorto, Virginia Avantaggiato, Jacques J. Tremblay, Domenico Lazzaro, Angela Di Carlo, Angela Mariano, Paolo Emidio Macchia, Giorgio Corte, Vincenzo Macchia, Jacques Drouin, Philippe Brûlet, Antonio Simeone

Research output: Contribution to journalArticle

Abstract

Genetic and molecular approaches have enabled the identification of regulatory genes critically involved in determining cell types in the pituitary gland and/or in the hypothalamus. Here we report that Otx1, a homeobox-containing gene of the Otx gene family, is postnatally transcribed and translated in the pituitary gland. Cell culture experiments indicate that Otx1 may activate transcription of the growth hormone (GH), follicle-stimulating hormone (βFSH, luteinizing hormone (βLH) and α-glycoprotein subunit (αGSU) genes. Analysis of Otx1 null mice indicates that, at the prepubescent stage, they exhibit transient dwarfism and hypogonadism due to low levels of pituitary GH, FSH and LH hormones which, in turn, dramatically affect downstream molecular and organ targets. Nevertheless, Otx1(-/-) mice gradually recover from most of these abnormalities, showing normal levels of pituitary hormones with restored growth and gonadal function at 4 months of age. Expression patterns of related hypothalamic and pituitary cell type restricted genes, growth hormone releasing hormone (GRH), gonadotropin releasing hormone (GnRH) and their pituitary receptors (GRHR and GnRHR) suggest that, in Otx1(-/-) mice, hypothalamic and pituitary cells of the somatotropic and gonadotropic lineages appear unaltered and that the ability to synthesize GH, FSH and LH, rather than the number of cells producing these hormones, is affected. Our data indicate that Otx1 is a new pituitary transcription factor involved at the prepubescent stage in the control of GH, FSH and LH hormone levels and suggest that a complex regulatory mechanism might exist to control the physiological need for pituitary hormones at specific postnatal stages.

Original languageEnglish
Pages (from-to)1229-1239
Number of pages11
JournalDevelopment
Volume125
Issue number7
Publication statusPublished - 1998

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Keywords

  • Cell specificity
  • Dwarfism
  • Hypogonadism
  • Mouse
  • Otx1
  • Pituitary hormone
  • Spermiogenesis

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Acampora, D., Mazan, S., Tuorto, F., Avantaggiato, V., Tremblay, J. J., Lazzaro, D., Di Carlo, A., Mariano, A., Macchia, P. E., Corte, G., Macchia, V., Drouin, J., Brûlet, P., & Simeone, A. (1998). Transient dwarfism and hypogonadism in mice lacking Otx1 reveal prepubescent stage-specific control of pituitary levels of GH, FSH and LH. Development, 125(7), 1229-1239.