GHRP-6 STIMULATES CALCIUM INCREASE AND GROWTH-HORMONE RELEASE IN HUMAN SOMATOTROPHS IN-VITRO

The present study investigated the in vitro effects of His-D-Trp-Ala-T rp-D-Phe-Lys-NH2 (GHRP-6) and Growth hormone (GH) releasing Factor (GR F) on the intracellular Ca2+ concentration ([Ca2+]i) and hormone secre tion in human pituitary tumor cells cultured from acromegalic patients . We found that the two peptides triggered Ca2+ and secretory response s in all seven adenoma cell populations. Both GHRP-6 and CRF were effi cient in inducing GH secretion in adenomas. Three different types of C a2+ responses to GHRP-6 were observed:monophasic, plateau phase and a combination of both resulting in a biphasic response. Our results sugg est that the monophasic responses and the first part of the biphasic r esponses were due to mobilization of inositol triphosphate (IP3)-sensi tive intracellular Ca2+ stores. The plateau phase and the second part of the biphasic responses resulted from activation of an influx of ext racellular Ca2+ via voltage sensitive Ca2+ channels by a protein kinas e C (PKC) dependent mechanism. Thus, in human somatotrophs, GHRP-6 act ivates a transduction pathway similar to that described for thyrotropi n-releasing hormone (TRH) in lactotrophs. This pathway involves IP3 an d diacyl glycerol (DG) production resulting in mobilization of intrace llular Ca2+ and PKC activation respectively. Our observations suggest that the relative involvement of the two phases of this dual mechanism differs from one adenoma to another.