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 c ycling women with increasing age. Design: Controlled clinical study. P atients: Nine younger (18 to 33 years) and nine older (41 to 46 years) healthy women. Setting: Tests were performed on the 22nd day of regul ar cycles. Intervention: All subjects were tested with GH-releasing ho rmone (GH-RH) (1 mg/kg body weight), the acetylcholinesterase inhibito r pyridostigmine (120 mg by mouth), the somatostatin inhibitor arginin e (30 g infused IV over a 30-minute period) alone, and the combination of GHRH plus arginine or GH-RR plus pyridostigmine. Main Outcome Meas ures: Glucose, cortisol, androgens, estrogens, thyroid hormones, and i nsulin growth-like factor (IGF-I) were measured in basal samples. Seru m GH levels were measured in samples taken before and over a 2-hour pe riod after drug administration. Results: All basal hormonal values wer e similar in younger and older women. Insulin growth-like factor-I lev els were lower in older women. The GH responses to GH-RH alone, pyrido stigmine alone, or the combination were lower in the older than in the younger group and were correlated negatively with age. In contrast, e ither arginine alone or GH-RH plus arginine produced similar GH respon ses in the two groups. Conclusion: These data indicate that the cholin ergic stimulatory regulation of GH release is reduced in older cycling women. Because acetylcholine inhibits hypothalamic somatostatin relea se, the reduced cholinergic tone in older subjects may result in an in creased somatostatinergic tone. Normalization in older women of the re duced GH response to GH-RH by arginine supports this hypothesis.