Effect of Potentiation of Cholinergic Tone by Pyridostigmine on the GH Response to GHRH in Elderly Men

Abstract

The plasma GH response to GHRH (100 μg i.v.) was evaluated either alone or after pretreatment with pyridostigmine (120 mg orally 1 h prior to GHRH) in 9 younger men (age range: 22–39 years) and in 9 healthy elderly men (age range: 63–77 years). On a different occasion, subjects were tested with pyridostigmine alone. Basal concentrations of glucose, cortisol, androgens, estrogens, thyroid hormones and GH were similar in all subjects, whereas insulin-like growth factor was lower in elderly men. The GH response to GHRH was significantly lower in the older (mean peak was 6 times higher than baseline) than in the younger group (mean peak was 11.3 times higher than baseline). The pretreatment with pyridostigmine induced a striking increase in the GH response to GHRH in the younger subjects (mean peak was 26 times higher than baseline), whereas it produced only a slight increase in the GHRH-induced GH response in elderly men (mean peak was 8.7 times higher than baseline). When pyridostigmine was given alone, plasma GH levels rose significantly in both groups; however, the pyridostigmine-stimulated GH response was significantly higher in younger (mean peak was 6 times higher than baseline) than in older subjects (mean peak was 2.5 times higher than baseline). These data indicate that the cholinergic stimulatory regulation of GH release is reduced in elderly subjects. Since acetylcholine inhibits hypo-thalamic somatostatin release, the reduced cholinergic tone in elderly subjects may result in an increased somatostatinergic tone.

Growth Hormone Responses to Low-Dose Physostigmine in Elderly vs. Young Women and Men

“…It will therefore be of interest to test postmenopausal women with the same low-dose PHYSO challenge before and during estrogen replacement therapy, as van Amelsvoort et al [13] did with PYRIDO. Elderly men with reduced circulating androgens before and during testosterone replacement therapy also should be studied, because decreased GH responses to both PHYSO and PYRIDO have been reported in elderly vs. young men [6,45] . Our future studies in elderly and young subjects also will address specifi c muscarinic and nicotinic components of cholinergic stimulation of GH and HPA axis hormones, based on our fi ndings in female and male laboratory animals [46,47] .…”