FURTHER EVIDENCE OF CHOLINERGIC IMPAIRMENT OF THE NEUROENDOCRINE CONTROL OF THE GH SECRETION IN DOWNS-SYNDROME

There are data indicating that cholinergic activity is precociously im paired in Down's syndrome (DS). On the other hand, acetylcholine as we ll as arginine (ARG) play a major stimulatory role in the neural contr ol of growth hormone (GH) secretion in humans, likely acting via the i nhibition of hypothalamic somatostatin release. The aim of the present study was to verify the effects of pyridostigmine (PD, 120 mg p.o.), a cholinesterase inhibitor, and ARG (0.5 g/kg i.v,) on the growth horm one-releasing hormone (GHRH) (1 mu g/kg i.v.)-induced GH rise in 15 ad ult patients with DS (M/F: 8/7; age 26.5 +/- 2.2 years, body mass inde x, BMI: 25.7 +/- 1.0 kg/m(2)) in which the potentiating effect of PD o n GH secretion has been reported to be reduced. The results in DS were compared to those in 15 normal subjects (NS) (M/F: 8/7; age: 30.0 +/- 1.3 years; BMI: 21.4 +/- 0.4 kg/m(2)). Basal GH and insulin growth fa ctor I (IGF-1) levels in DS (1.8 +/- 0.7 and 206.5 +/- 21.0 mu g/l) we re similar to those in NS (1.4 +/- 0.3 and 179.4 +/- 11.0 mu g/l). The GPI response to GHRH alone in DS (526.5 +/- 120.1 mu g/l/h) was lon e r (p < 0.05) than that recorded in NS (895.4 +/- 153.7 mu g/l/h). The GHRH-induced GH rise was potentiated by PD both in DS (1.138 +/- 184.2 mu g/l/h; p < 0.02 vs. GHRH alone) and in NS (2.213.8 +/- 212.8 mu g/ l/h p < 0.005 vs, GHRH alone), however, as the percent potentiating ef fect of PD was similar in both groups (215 and 247%, respectively) the GH response to GHRH+PD in DS was lower (p < 0.005) than that in NS. T he GHRH-induced GH rise was also potentiated by ARG in both DS (2,243 +/- 362.4 mu g/h: p < 0.001 vs, GHRH alone) and NS (2,764.3 +/- 325.7 mu g/l/h, p < 0.005 vs. GHRH alone), As the percent potentiating effec t of ARG in DS was more marked than in NS (425 vs, 308%, respectively) , the GH response to GHRH+ARG became similar in both groups, No sex-re lated difference was found in the GH response to various stimuli both in DS and NS, In conclusion, these data demonstrate that the potentiat ing effect of PD but not that of ARG is impaired in adults with DS in whom a reduced somato-trope responsiveness to GHRH is present. These f indings indicate that in DS the pituitary GPI releasable pool is fully preserved while an impairment of the tuberoinfundibular cholinergic p athways could lead to somatostatinergic hyperactivity and low somatotr ope responsiveness to GHRH.