Wnt signalling in oestrogen-induced lactotroph proliferation
J. Davis & G. Brabant
The anterior pituitary gland displays considerable plasticity with a proliferative response to oestrogen in a number of different situations including pregnancy. The nature of pituitary remodelling to this physiological demand is not clear.
Using microarray analysis we found that oestrogen treatment of the rat in vivo increased expression of Wnt4 mRNA in adult rat pituitary tissue. Dual immunofluorescence analysis showed that this Wnt4 expression was not confined to lactotrophs but was expressed in all anterior pituitary cell types. Reporter gene assays for canonical Wnt signalling action on transcription showed no effect of Wnt4 or other activators in pituitary lactotrophic GH3 cells, suggesting that an alternative pathway might be in operation. No nuclear localisation of beta-catenin was detected under any conditions in either GH3 cells or normal rat anterior pituitary cells. On the other hand Wnt4 did inhibit calcium oscillations in GH3 cells, indicating that a non-canonical pathway may be activated in the mature lactotrophic cell. Immunocytochemical studies showed that Wnt4 was particularly strongly expressed in the marginal zone, a region of the pituitary containing progenitor cells expressing Sox9. Studies in normal human pituitary tissue showed higher expression of Wnt4 staining in the lateral aspects of the pituitary but no counterpart to this marginal zone expression was clearly identifiable. Wnt4 immunostaining was seen in all types of pituitary adenoma including prolactinomas and somatotroph adenomas, and was weakest in corticotroph adenomas.
In summary Wnt4, a known developmental regulator in the fetal pituitary, is increased during oestrogen-induced pituitary proliferation. It acts through non-canonical signalling pathways in the mature pituitary lactotroph. Wnt4 is expressed in a variety of different human pituitary adenomas, though its role in their pathogenesis remains unclear.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details are unavailable.