Direct action of growth hormone-releasing hormone agonist JI-38 on normal human fibroblasts: evidence from studies on cell proliferation and c-myc proto-oncogene expression.

Growth hormone-releasing hormone (GHRH) is secreted by the hypothalamus and stimulates the release of growth hormone from the pituitary. Recent studies also indicate that in addition to its neuroendocrine function, GHRH may play a direct role in the proliferation of cancer cells, acting as growth factor for various human tumors. In the present study we investigated the effects of JI-38, an agonistic analog of GHRH, on the rate of proliferation of normal human diploid dermal fibroblasts (NHF) cultured in vitro. The effects of JI-38 on the levels of mRNA for c-myc proto-oncogene were also tested. Exposure to 10(-7) M JI-38 stimulated the rate of proliferation of early passage NHF by about 100%. Exposure of NHF cells to 10(-8)-5x10(-6) M JI-38 for 24 h resulted in about 0.5-3.5 fold increase in the levels of mRNA for c-myc proto-oncogene. The ability of JI-38 to stimulate the proliferation of NHF cells was abolished in cells cultured at late passage. Continuous exposure to 10(-7) M JI-38, over 6-7 passages (15-20 population doublings), progressively reduced the rate of proliferation of NHF compared with cells exposed to medium alone, indicating that GHRH agonist acted as a growth inhibitor. Our results suggest that at certain developmental stages, GHRH may act on various tissues, stimulating cell proliferation.