Modulation of the tyrosine kinase receptor Ret/glial cell-derived neurotrophic factor (GDNF) signaling: a new player in reproduction induced anterior pituitary plasticity?

Endocrinology. 2011 Feb;152(2):515-25. doi: 10.1210/en.2010-0673. Epub 2011 Jan 14.


During gestation, parturition, and lactation, the endocrine axis of the dam must continually adapt to ensure the continual and healthy development of offspring. The anterior pituitary gland, which serves as the endocrine interface between the brain and periphery, undergoes adaptations that contribute to regulation of the reproductive axis. Growth factors and their receptors are potential candidates for intrapituitary and paracrine factors to participate in the functional and anatomical plasticity of the gland. We examined the involvement of the growth factor glial cell-derived neurotrophic factor (GDNF) and its receptor tyrosine kinase rearranged during transfection (Ret) in the physiological functional and anatomical plasticity of the anterior pituitary gland. We found that variations in both expression and subcellular localization of Ret during gestation and lactation are temporally correlated with changes in pituitary gland function. We showed that Ret/GDNF signaling could endorse two different functional roles depending on the physiological status. At the end of lactation and after weaning, Ret was colocalized with markers of apoptosis. We found that Ret could therefore act as a physiological dependence receptor capable of inducing apoptosis in the absence of GDNF. In addition, we identified the follicullostellate cell as a probable source for intrapituitary GDNF and proposed GDNF as a potential physiological modulator of endocrine cell function. During all stages studied, we showed that acute application of GDNF to pituitary slices was able to modulate both positively and negatively intracellular calcium activity. Altogether our results implicate Ret/GDNF as a potent pleiotropic factor able to influence pituitary physiology during a period of high plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Glial Cell Line-Derived Neurotrophic Factor / genetics
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism*
  • Immunohistochemistry
  • Lactation / genetics
  • Lactation / metabolism
  • Lactotrophs / metabolism
  • Mice
  • Microscopy, Electron
  • Pituitary Gland / cytology
  • Pituitary Gland / metabolism*
  • Pituitary Gland / ultrastructure
  • Polymerase Chain Reaction
  • Pregnancy / genetics
  • Pregnancy / metabolism
  • Proto-Oncogene Proteins c-ret / genetics
  • Proto-Oncogene Proteins c-ret / metabolism*
  • Reproduction / genetics
  • Reproduction / physiology*
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Somatotrophs / metabolism
  • Weaning


  • Glial Cell Line-Derived Neurotrophic Factor
  • Proto-Oncogene Proteins c-ret
  • Ret protein, mouse