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

Abstract

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)

Neuropeptide Y directly inhibits growth hormone secretion by human pituitary somatotropic tumours

“…increase in GH secretion over controls varied between 35 and 86%, depending on the tumour. This variability in response of different GH se¬ creting human pituitary tumours has been previ¬ ously described by a number of authors Oosterom et al 1984;Ishibashi & Yamaji 1985;White et al 1985). NPY (25 nmol/1) reduced the effect of GHRH in each experiment, although GH was still stimulated when compared with cul¬ tures treated with NPY alone, and the GH re¬ sponse curves to GHRH in the presence or ab¬ sence of NPY were parallel.…”

Influence of Coexisting Hypothalamic Messengers on Growth Hormone Secretion from Rat Anterior Pituitary Cells in vitro

“…However, more recent investigations indicate that DA and DA agonists reduce the rate of GH release from GH-secreting somatotrophinomas in vitro [1,31,35, 40,60,63]. The physiological relevance of these findings has however been questioned, since tumor cells might express ectopic DA receptors.…”

“…In contrast to these studies, we were not able to detect any significant alteration in basal GH release after the addition of DA. The same negative results have also been reported by Law et al [34], using ovine pituitary cells.An inhibitory effect on GRF-stimulated GH release has been demonstrated in long-term incubations of rat pituitary cells with the DA agonist bromocriptine [14], Inhibition of GRF-stimulated GH secretion by DA has recently been reported by Law et al [34] and White et al [63], which stud ied the effect of human pancreatic GRF forms and DA on GH release from ovine and human pituitary tumor cells, respectively. In the rat, however, no inhibitory effect of DA on GRF-stimulated GH secretion has been demonstrated in studies with a tumor medium containing human GRF [13].…”

Long-term effects of a gonadotrophin-releasing hormone agonist ([d-Ser(But)6]GnRH(1–9)nonapeptide-ethylamide) on gonadotrophin secretion from human pituitary gonadotroph cell adenomas in vitro

“…Human pituitary adenoma tissue was obtained from one male and two female patients (Table 1) at trans-sphenoidal hypophysectomy and dispersed as described previously (White, Daniels, Kendall-Taylor et al 1985). Erythrocytes were removed by centri¬ fugation of the cell suspension for 5 min at 400 g on a layer of 60% (v/v) Percoli (Sigma Chemical Com¬ pany, Poole, Dorset, U.K.) diluted in medium.…”

“…Between 12 500 and 39 300 viable cells (viability > 98%) per mg wet weight of tissue were obtained and cultures were established in glass tubes as before (White et al 1985) (tumours 1 and 2) or in plastic mul¬ tiwell dishes (Flow Laboratories, Irvine Strathyclyde, U.K.) (tumour 3) containing 40 105, 2-7 IO5 and 2-0 5 cells/culture respectively. All three tumours displayed positive immunohistochemical staining for, and complementary in-vitro secretion of, lutei¬ nizing hormone (LH), follicle-stimulating hormone (FSH) and subunit, but no other anterior pituitary hormones.…”