Pituitary-adrenocortical responses to the chronic administration of granulocyte colony-stimulating factor in rats

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor, but it may play a role in the regulation of the neuroendocrine system activity. Only few data are available about its possible influence on the pituitary gland. We have recently reported an acute stimulatory effect of G-CSF (and of GM-CSF) on adrenocorticotropic hormone (ACTH) secretion in rats in vivo. The purpose of the present study was to evaluate whether chronic administration of G-CSF affects ACTH and corticosterone secretion and growth processes of the rat anterior pituitary gland and adrenal cortex in vivo. We have demonstrated that G-CSF (at a dose of 10.0 microg/kg body weight (BW)) injected s.c. once daily (for 7 days), stimulated both ACTH and corticosterone secretion. Simultaneously, G-CSF treatment did not change the total anterior pituitary cell proliferation as revealed by immunohistochemical staining of proliferating cell nuclear antigen (PCNA). On the other hand, proliferative activity of corticotrophs, detected in the sections of the anterior pituitary using double-labeling. was significantly increased after treatment with G-CSF. Moreover, this growth factor induced an increase in the proliferation ratio in the entire adrenal equatorial section. These findings suggest an involvement of G-CSF in the regulation of pituitary-adrenal axis and support the hypothesis of bidirectional associations between the immune system and the endocrine glands.