Effects of the gp130 cytokines ciliary neurotropic factor (CNTF) and interleukin-11 on pituitary cells: CNTF receptors on human pituitary adenomas and stimulation of prolactin and GH secretion in normal rat anterior pituitary aggregate cultures

Two of the most potent cytokines regulating anterior pituitary cell functio n are leukemia inhibitor); factor (LIF) and interleukin (IL)-6, which belon g to the cytokine family using the common gp130 signal transducer. Recently , the expression and action of two other members of this family, IL-11 and ciliary neurotrophic factor (CNTF). on different cell lines has also been d emonstrated, We studied the expression of the specific receptor subunits fo r CNTF in mammotropic, non-functioning and somatotropic tumors and the acti on of CNTF and IL-11 in the regulation or hormone secretion in these and no rmal pituitary cells. The mRNA for the cr chain specific for the CNTF recep tor was detected by Northern blot in tumors secreting prolactin (PRL) and G H and in non-functioning tumors. We found that both IL-11 and CNTF exerted a similar stimulatory effect oil GH mRNA expression in somatotropic monolay er cell cultures from acromegalic tumors, but these cytokines had no signif icant influence oil GH secretion. CNTF stimulates prolactin secretion in la ctotropic monolayer cell cultures from patients with prolactinoma. In monol ayer cell cultures from normal rat anterior pituitary, IL-11 and CNTF had n o significant effect on the release of either CH or PRL, or on GH mRNA. How ever, when the cells were cultured in aggregate cultures, in which the thre e-dimensional structure of the cells is reconstituted, both cytokines, in d oses at which they had no effect on monolayer cultures, significantly stimu lated both PRL and GH secretion. These data show that IL-11 and CNTF may ac t as regulatory factors in anterior pituitary cells, in which the three-dim ensional structure of the gland is of critical importance.