In obesity the somatotrope response to either growth hormone-releasing hormone or arginine is inhibited by somatostatin or pirenzepine but not by glucose.

Abstract

It is known that spontaneous and stimulated GH secretion is reduced in obesity. On the other hand, it has been recently reported that, in obese subjects, plasma GH levels did not change during a hyperglycemic clamp. To further study the sensitivity of somatotrope cells to inhibitory influences in obesity, we studied the effect of somatostatin, pirenzepine, or glucose on the GH response to GHRH or arginine in 32 obese patients and 30 controls. Basal GH levels were lower in obese than in normal subjects (1.0 +/- 0.6 vs. 4.8 +/- 0.7 micrograms/L, P < 0.05), while insulin-like growth factor-I levels were similar in both groups (137.3 +/- 13.2 vs. 138.8 +/- 12.2 micrograms/L). In obese as well as in control subjects pirenzepine abolished the GH response to either GHRH (AUC0-120: 43.7 +/- 9.6 vs. 258.3 +/- 59.9 micrograms/L/h, P < 0.04 and 113.0 +/- 75.0 vs. 870.5 +/- 255 micrograms/L.h, P < 0.01, respectively) or arginine (6.5 +/- 2.5 vs. 118.7 +/- 55.9 micrograms/L.h, P < 0.05 and 47.7 +/- 7.3 vs. 334.0 +/- 157.5 micrograms/L.h, P < 0.01, respectively). Differently from pirenzepine, glucose blunted the GH response to either GHRH or arginine in control subjects (260.8 +/- 38.3 vs. 479.5 +/- 83.9 micrograms/L.h, P < 0.03 and 294.8 +/- 46.3 vs. 625.1 +/- 139.1 micrograms/L.h, P < 0.05, respectively), but failed to modify it in obese patients (193.7 +/- 39.4 vs. 172.4 +/- 33.6 micrograms/L.h and 121.1 +/- 43.4 vs. 155.1 +/- 39.7 micrograms/L.h, respectively). On the other hand, somatostatin deeply blunted the GHRH-induced GH release in obese patients (58.5 +/- 25.4 vs. 548.7 +/- 196.6 micrograms/L.h, P < 0.05) as well as in controls (181.4 +/- 44.4 vs. 759.7 +/- 46.6 micrograms/L.h, P < 0.04). In conclusion, our results show that, in obesity, the stimulated GH release is refractory to the inhibitory effect of glucose but not of pirenzepine, in spite of their likely common mechanism of action, i.e. increase of hypothalamic somatostatin release. Exogenous somatostatin is able to abolish GH secretion both in normal and obese subjects. These data suggest the existence of a peculiar inhability of hyperglycemia to trigger somatostatinergic release in obesity.

Energy homeostasis targets chromosomal reconfiguration of the human GH1 locus

“…Our findings indicate that hGH production is extremely sensitive to increased caloric intake within the continuum of obesity progression. Impaired spontaneous secretion of hGH and declined somatotroph responsiveness to all known pharmacological provocative stimuli in obese humans has been previously reported (1,(45)(46)(47)(48). This suppression of hGH can occur as a result of impaired GH secretagogue signaling at the level of the somatotroph; however, it can also be explained in terms of decreased hGH synthesis and insufficient reserves for secretion in response to treatment with the GH secretagogue.…”

Growth hormone in obesity

“…On the contrary, the somatotropin response to GHRH and arginine is physiologically blunted by administration of SRIH and of the cholinergic antagonist pirenzepine. 84 These observations suggest an inability of hyper-glycaemia to trigger hypothalamic SRIH release in obesity. …”

Effects of arginine, growth hormone-releasing hormone (GHRH) and neostigmine administered singly or in paired combinations on growth hormone (GH) release in pigs

“…Cholinesterase inhibitors, such as neostigmine (NEO) and pyridostigmine, which are known to decrease somatostatin release (Richardson et al, 1980;Muller, 1987) do not further increase GH response to ARG in human (Massara et al, 1986;Ghigo et al, 1990aGhigo et al, , 1994Procopio et al, 1995). On the contrary, the effect of ARG on GH secretion is blunted or abolished by cholinergic antagonists such as atropine (Casanueva et al, 1984) and pirenzepine (Delitala et al, 1982;Maccario et al, 1995), an acute increase in free fatty acids (Maccario et al, 1994) and an administration of a somatostatin analog (Masuda et al, 1990). …”