The Insulin-Like Growth Factor I Generation Test: Resistance to Growth Hormone With Aging and Estrogen Replacement Therapy

Abstract

Circulating IGF-I is primarily regulated by growth hormone, but other factors such as nutritional status may also influence IGF-I secretion. The effects of age, gender, and estrogen replacement on responsiveness of serum IGF-I to GH administration have not been directly studied. The high-affinity circulating GH-binding protein (GHBP) has the same structure as the extracellular domain of the GH receptor and may reflect the sensitivity to GH in humans. To examine these issues, we employed an IGF-I generation test in which a single dose of GH (0.1 mg/kg SQ) was administered to 31 healthy adults comprising five groups: young (20-29 years) males (YM), young females in the follicular phase of the menstrual cycle (YF), older (60-69 years) males (OM), older females not on estrogen replacement (OFN), and older females on oral estrogen replacement (OFE). Blood was sampled for IGF-I and GHBP over 72 hours following GH administration. OM had lower peak IGF-I levels (323 +/- 38 vs. 497 +/- 85 micrograms/l, p = 0.0015) and a lower IGF-I response to GH (delta IGF-I: 187 +/- 33 vs. 293 +/- 57 micrograms/l, p = 0.0085) than YM. OFE had lower basal IGF-I (63 +/- 11 vs. 133 +/- 19 micrograms/l, p = 0.0046), peak IGF-I (174 +/- 28 vs. 400 +/- 40 micrograms/l, p = 0.0015), and delta IGF-I (111 +/- 21 vs. 268 +/- 27 micrograms/l, p = 0.0085) than OFN. IGFBP-3 levels were unchanged 24 hours after GH administration.(ABSTRACT TRUNCATED AT 250 WORDS)