EFFECTS OF CORTICOTROPIN-RELEASING HORMONE, VASOPRESSIN AND INSULIN-LIKE GROWTH-FACTOR-I ON PROLIFERATION OF AND ADRENOCORTICOTROPIC HORMONE-SECRETION BY CANINE CORTICOTROPIC ADENOMA CELLS IN-VITRO

Extrinsic factors such as hypothalamic hormones or intrapituitary grow th factors may stimulate clonal expansion of a genomically altered cel l and therefore play a role in pituitary tumorigenesis, Here we report on the effects of the hypophysiotrophic hormones corticotrophin-relea sing hormone (CRH) and vasopressin (AVP) and the intrapituitary growth factor insulin-like growth factor-I (IGF-I) on the proliferation of, as measured by the bromodeoxyuridine labelling index, and ACTH secreti on by normal canine pituitary cells and corticotrophic adenoma cells o f dogs with pituitary-dependent hyperadrenocorticism. The sensitivity to inhibition by cortisol was analysed under various conditions. Under basal conditions, no significant differences were found in the bromod eoxyuridine labelling indices between control cells and tumour cells. CRH, AVP, IGF-I and cortisol had no effect on the proliferation of can ine pituitary cells or canine corticotrophic adenoma cells. In contras t with normal pituitary cells, the proliferation of corticotrophic ade noma cells was stimulated by fetal calf serum (FCS). This FCS-induced proliferation was not inhibited by cortisol. The CRH-induced ACTH secr etion by corticotrophic adenoma cells was significantly (P < 0.05) low er than that by normal pituitary cells after 4 h incubation with CRH, Incubation with cortisol for 24 h resulted in reduced ACTH secretion u nder basal and AVP- or IGF-I-stimulated conditions. The relative inhib ition was, however, significantly (P < 0.05) lower in ACTH-producing t umour cells than in normal pituitary cells. Cortisol did not inhibit t he CRH-induced ACTH secretion in normal pituitary cells after 24 h. In conclusions canine corticotrophic adenomas are less sensitive to stim ulation by CRH and less sensitive to inhibition by glucocorticoids. Th ese tumours have an aberrant sensitivity to a growth-promoting factor present in FCS, This factor may have an important role in the growth p romotion of canine corticotrophic tumours.