Effects of growth hormone-releasing factor (1-44) on growth hormone release from human somatotrophinomas in vitro: interaction with somatostatin, dopamine, vasoactive intestinal peptide and cycloheximide.
The effect of GH-releasing factor(1-44)(GRF) alone, or together with somatostatin (SRIF), dopamine (DA), vasoactive intestinal peptide (VIP) or cycloheximide was studied in a total of ten human somatotrophinomas using a static cell culture system. Growth hormone-releasing factor (2.0 X 10(-8) mol/l) significantly (P less than 0.05) stimulated GH release from nine out of ten tumours over 4-h incubations, and a dose-related effect (2.0 X 10(-10) -2.0 X 10(-8) mol/l) was observed in five tumours thus studied. Repeated GRF (2.0 X 10(-8) mol/l)-mediated GH release was seen during 96% (n = 25) of experiments performed on six tumours over 4 h and up to 27 days in culture. Growth hormone-releasing factor (2.0 X 10(-8) mol/l) also stimulated GH release from five out of seven somatotrophinomas during 60-min incubations. Somatostatin (6.1 X 10(-9) mol/l) completely inhibited GRF-induced GH secretion from four tumours studied over 4 h, but in each case there was significant (P less than 0.05) 'rebound' of GH release from cultures exposed to both GRF and SRIF during a subsequent recovery period. Dopamine suppressed basal GH release from two out of four tumours, but in each case had a greater inhibitory effect on GRF-mediated GH release. Vasoactive intestinal peptide directly stimulated GH release from two out of three tumours, and the effects were additive to maximal stimulatory doses of GRF. Cycloheximide significantly (P less than 0.01) enhanced GRF-stimulated release of GH during a 60-min incubation, but inhibited both basal and GRF-stimulated release over 4 and 8 h.(ABSTRACT TRUNCATED AT 250 WORDS)
White
M C
MC
Daniels
M
M
Kendall-Taylor
P
P
Turner
S J
SJ
Mathias
D
D
Teasdale
G
G
D002478:Cells, Cultured; D003513:Cycloheximide / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects; D010911:Pituitary Neoplasms / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D010446:Peptide Fragments; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D003513:Cycloheximide; D004298:Dopamine