Contributions of gender and systemic estradiol and testosterone concentrations to maximal secretagogue drive of burst-like growth hormone secretion in healthy middle-aged and older adults.

To test whether concentrations of estradiol and testosterone predict GH responses to mechanistically distinct secretagogues in healthy older adults, we studied 16 volunteers (n = 10 men, n = 6 women, age 49-72 yr) in each of six randomly ordered sessions as follows: 1) saline; 2) l-arginine; 3) aerobic exercise; 4) GHRH; 5) GH-releasing peptide (GHRP)-2; and 6) somatostatin-induced rebound. Statistical comparisons disclosed that stimulus type (P < 0.001) and the interaction between gender and stimulus type (P = 0.023) determine GH secretion. In women, each secretagogue, except exercise and somatostatin-induced rebound, stimulated GH secretion by 2.6- to 6.4-fold over saline/rest (P < 0.023). In men, somatostatin-induced rebound drove GH secretion by 4.6-fold (P = 0.004), exercise by 16-fold (P < 0.001), and other secretagogues by 18- to 109-fold over saline/rest (each P < 0.001). Gender comparisons disclosed greater GH secretion in men than women after somatostatin-induced rebound (P = 0.008) and GHRP-2 injection (P < 0.001) and conversely greater GH secretion in women than men after saline (P = 0.013). Regression analysis showed that individual concentrations of estradiol (r = 0.80, P = 0.002) and testosterone (r = 0.63, P = 0.008) and their combination (r = 0.86, P < 0.001) strongly predict responses to GHRP-2 only. We conclude that among healthy middle-aged and older adults, the action of GHRP is uniquely determined by gender and physiological concentrations of testosterone and estradiol.

Single and combined effects of growth hormone and testosterone administration on measures of body composition, physical performance, mood, sexual function, bone turnover, and muscle gene expression in healthy older men.

We examined the effects of GH and/or testosterone (T) administration on body composition, performance, mood, sexual function, bone turnover, and muscle-gene expression in healthy older men. Ten men [mean (SEM) age, 68 (2.5) yr; height, 171.5 (2.4) cm; and weight, 80 (3.0) kg] completed each of the following 1-month, double-blind interventions after a baseline (B) study in randomized order with an intervening 3-month washout: transdermal T patch (5.0 mg/daily); recombinant human GH (6.25 micro g/kg sc daily); and combined hormones (GHT). ANOVA with repeated measures was used to evaluate interventional effects. Integrated serum GH concentrations [mean (SEM)] were elevated comparably by GH and GHT: [B = 363 (55), GH = 1107 (120), T = 459 (131), and GHT = 1189 (46) micro g/liter.min; P < 0.0001]. Serum IGF-I concentrations also increased commensurately after GH and GHT: [B = 168 (14), GH = 285 (16), T = 192 (25), and GHT = 294 (25) micro g/liter; P < 0.0001]. GHT administration increased total estradiol: [B = 110 (20), GH = 106 (13), T = 129 (13), and GHT = 153 (17) pmol/liter; P < 0.02], and both T and GHT elevated free T: [B = 12 (2.1), GH = 11 (1.5), T = 22 (2.8), and GHT = 24 (2.5) pg/ml; P < 0.0001]. No significant changes occurred in strength, flexibility, percentage body fat, or sexual function and mood. However, fat-free mass increased under combined GHT exposure: [B = 55 (1.3), GH = 56 (1.1), T = 55 (1.5), GHT = 57 (1.7) kg; P < 0.03]. Balance improved in response to GH intervention (P < 0.05), as did 30-m walk time during T and GHT interventions [B = 6.6 (0.3), GH = 6.2 (0.7), T = 5.9 (0.3), GHT = 5.5 (0.3) sec; P = 0.04] and stair climb time for all three interventions [B = 32.2 (1.4), GH = 29.8 (1.2), T = 30.5 (1.4), and GHT = 29.9 (1.2) sec (P = 0.0034), wherein the effects of GH, T, and GHT were different from that of B]. Muscle IGF-I gene expression increased by 1.9-fold during GH administration and by 2.3-fold during GHT administration (P < 0.05, compared with B). Myostatin and androgen receptor gene expression were not affected. Serum osteocalcin increased in response to the GH and GHT interventions: [B = 4.8 (0.52), GH = 5.7 (0.54), T = 4.7 (0.33), and GHT = 5.5 (0.39); P <0.009]. There were no significant adverse events during 30 patient-months of intervention. We conclude that 1 month of GH and/or T administration improves certain measures of balance and physical performance in older men and increases muscle IGF-I gene expression.