Effects of growth hormone and/or sex steroid administration on whole-body protein turnover in healthy aged women and men

Abstract

Aging is associated with reduced activities of the growth hormone (GH), insulin-like growth factor I (IGF-I), and sex steroid axes, and with decreased lean body mass and protein synthesis. Using a randomized, double-blinded, placebo-controlled design, we studied the effects of 6 months of administration of GH alone, sex hormone alone (hormone replacement therapy in women, testosterone enanthate [T] in men), or GH plus sex hormone on protein turnover in healthy men (n = 60) and women (n = 43), aged 65 to 88 years (mean, 71 ± 4.4 years). Growth hormone administration significantly increased IGF-I levels in both sexes, more markedly in men. Sex steroid administration increased the levels of estrogen and testosterone in women and men, respectively ( P = .05). Protein turnover was measured before and after the 26-week treatment period by means of a primed, constant l-[1- 13C]leucine infusion. In men, GH plus T administration increased leucine flux from 80.2 ± 2.8 to 93.6 ± 4.2 μmol · h −1 · kg −1 ( P = .02). Leucine oxidation did not change significantly after hormone treatment in either sex. Growth hormone treatment led to nonsignificant upward trends in nonoxidative leucine disposal in men (9.1 ± 5.2 mol · h −1 · kg −1) and women (7.6 ± 7.1 mol · h −1 · kg −1). Among all groups combined, changes in nonoxidative leucine disposal were directly related to those of serum IGF-I level ( r = 0.248, P < .02). Whole-body protein turnover increased in GH plus T–treated men (0.6 ± 0.2 g protein · kg −1 · d −1; P < .01). These data suggest that low-dose GH administration increases protein synthesis in healthy aged women and men, and that the coadministration of testosterone plus GH enhances this effect in elderly men.