Age-dependent decrease in the growth hormone response to growth hormone-releasing hormone in normally cycling women.
OBJECTIVE: To establish possible changes in GH secretion in normally cycling women with increasing age. DESIGN: Controlled clinical study. PATIENTS: Nine younger (18 to 33 years) and nine older (41 to 46 years) healthy women. SETTING: Tests were performed on the 22d day of regular cycles. INTERVENTION: All subjects were tested with GH-releasing hormone (GH-RH) (1 mg/kg body weight), the acetylcholinesterase inhibitor pyridostigmine (120 mg by mouth), the somatostatin inhibitor arginine (30 g infused IV over a 30-minute period) alone, and the combination of GH-RH plus arginine or GH-RH plus pyridostigmine. MAIN OUTCOME MEASURES: Glucose, cortisol, androgens, estrogens, thyroid hormones, and insulin growth-like factor (IGF-I) were measured in basal samples. Serum GH levels were measured in samples taken before and over a 2-hour period after drug administration. RESULTS: All basal hormonal values were similar in younger and older women. Insulin growth like factor-I levels were lower in older women. The GH responses to GH-RH alone, pyridostigmine alone, or the combination were lower in the older than in the younger group and were correlated negatively with age. In contrast, either arginine alone or GH-RH plus arginine produced similar GH responses in the two groups. CONCLUSION: These data indicate that the cholinergic stimulatory regulation of GH release is reduced in the older cycling women. Because acetylcholine inhibits hypothalamic somatostatin release, the reduced cholinergic tone in other subjects may result in an increased somatostatinergic tone. Normalization in older women of the reduced GH response to GH-RH by arginine supports this hypothesis.