Influence of growth and transcriptional factors, and signaling molecules on early human pituitary development.

Development and differentiation of the human pituitary gland was investigated in 6 human conceptuses 6-9 postovulatory weeks old, using immunohistochemical technique to investigate appearance of different developmental factors, and immunofluorescent double staining technique with Ki-67 to investigate proliferation. In the developing human pituitary gland, different developmental factors appeared in temporally and spatially restricted patterns, thus contributing to formation of different parts of the gland: adenohypophysis, neurohypophysis and associated mesenchyme. Some growth factors were not primarily involved in cell proliferation (TGF-ss, BMP-2/4 and GATA), but in differentiation of pituitary cells: TGF-ss, BMP-2/4 and GATA probably contributed to differentiation of cells in the mesenchyme at earlier stages, while their influence on differentiation of specific cell types in the adenohypophysis increased with development. At later developmental stages, those factors also influenced the differentiation of cells in the neurohypophysis. FGF-8 and FGF-10 probably participated both in the growth and differentiation of pituitary cells: while FGF-8 could act during early developmental stages, FGF-10 participated in the same processes at later stages of pituitary development. Expression of EGF and VEGF indicated their involvement in proliferation of initially differentiated pituitary cells, and in subsequent differentiation of some cell types in the adenohypophysis and neurohypophysis. In the mesenchyme, expression of VEGF might be related to formation of new blood vessels as well. Precise patterns of appearance of growth and transcription factors, and signaling molecules in developing human pituitary gland seem to be important for cell proliferation, differentiation, and normal morphogenesis of the gland.