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

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth fac tor, 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 p ituitary 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 growt h processes of the rat anterior pituitary gland and adrenal cortex in vivo. We have demonstrated that G-CSF (at a dose of 10.0 mu g/kg body weight (BW )) injected s.c. once daily (for 7 days), stimulated both ACTH and corticos terone secretion. Simultaneously, G-CSF treatment did not change the total anterior pituitary cell proliferation as revealed by immunohistochemical st aining of proliferating cell nuclear antigen (PCNA). On the other hand, pro liferative activity of corticotrophs, detected in the sections of the anter ior pituitary using double-labeling, was significantly increased after trea tment with G-CSF. Moreover, this growth factor induced an increase in the p roliferation ratio in the entire adrenal equatorial section. These findings suggest an involvement of G-CSF in the regulation of pituitary-adrenal axi s and support the hypothesis of bidirectional associations between the immu ne system and the endocrine glands. (C) 2000 Published by Elsevier Science B.V. All rights reserved.