CORTISOL INHIBITION OF GROWTH HORMONE-RELEASING HORMONE-STIMULATED GROWTH-HORMONE RELEASE FROM CULTURED SHEEP PITUITARY-CELLS

Cortisol inhibits growth hormone (GH) release in short-term culture an d is stimulatory in long-term cultures of rat and human pituitary cell s. This study sought to determine the in vitro effects of cortisol on GH release and the signal transduction pathways mediating the effects of cortisol on GH release from cultured ovine somatotrophs. Pituitary cells were dispersed with collagenase and placed in culture medium for 4 days. The data indicate that cortisol inhibited growth hormone-rele asing hormone (GHRH)-stimulated GH release by at least 2 h. In short-t erm culture GHRH-, forskolin- and dibutyryl cyclic AMP-stimulated GH r elease were inhibited by cortisol, suggesting an effect distal to the membrane and involving a protein kinase A (PKA)-dependent pathway. GH release initiated by KCl was inhibited by cortisol, but GH release cau sed by the calcium ionophore A23187 was unaffected. This suggests a po ssible action of cortisol on the calcium channels. The inhibition by c ortisol of the calcium-dependent secretion of GH release appeared to p lay a smaller role in mediating cortisol inhibition of GH release than that seen with PKA. Attempts to overcome cortisol inhibition of GH re lease using puromycin, arachidonic acid or pertussis term were unsucce ssful Since cortisol inhibition of GH release does not occur via the m echanisms found in other cell types, cortisol inhibition of pituitary cell secretions appears to be cell-specific rather than utilizing a si ngle inhibitory mechanism. The majority of cortisol actions on the som atotroph appear to act at a site distal to the production of cyclic AM P. In contrast to man and the rat, the sheep somatotroph does not appe ar to increase GH release when treated with cortisol for 24 h, perhaps related to the lack of effect of cortisol on somatotroph content of G H.