Aromatase and 5alpha-reductase inhibition during an exogenous testosterone clamp unveils selective sex steroid modulation of somatostatin and growth hormone secretagogue actions in healthy older men.
Veldhuis. Johannes D JD; Mielke. Kristi L KL; Cosma. Mihaela M; Soares-Welch. Cacia C; Paulo. Remberto R; Miles. John M JM; Bowers. Cyril Y CY
Key Findings
- Testosterone directly raises both baseline and peak GH levels, especially when GHRP‑2 is given.
- Estradiol reduces the GH response to a combined stimulus (GHRH + GHRP‑2 + L‑arginine).
- DHT is positively linked to GH pulses during somatostatin infusion, indicating it supports GH release in certain contexts.
Practical Outcomes
- If you’re using GHRP‑2 to raise GH, keep your testosterone levels up – this will likely enhance the peptide’s effect. Be cautious with strong aromatase inhibitors, as lowering estradiol too much might blunt some GH‑boosting pathways. Manipulating DHT (e.g., with 5α‑reductase blockers) could affect GH responses depending on the other secretagogues you’re using, so consider the overall hormonal balance rather than targeting a single pathway.
Summary
In older men, higher testosterone levels boost the amount of growth hormone (GH) released when you use GHRP‑2, while the hormone estradiol can actually dampen the GH response. Dihydrotestosterone (DHT) also helps GH release in some situations. Changing how much testosterone is turned into DHT or estradiol (by using drugs that block those pathways) shifts how well GHRP‑2 works.
Abstract
How endogenous testosterone (Te), 5alpha-dihydrotestosterone (DHT), and estradiol (E(2)) regulate pulsatile GH secretion is not understood. Conversion of Te to androgenic (Te-->DHT) or estrogenic (Te-->E(2)) products directs GH secretion. SUBJECTS AND LOCATION: Healthy older men (N = 42, ages 50-79 yr) participated at an academic medical center. We inhibited 5alpha-reduction with dutasteride and aromatization with anastrozole during a pharmacological Te clamp and infused somatostatin (SS), GHRH, GH-releasing peptide-2 (GHRP-2), and L-arginine/GHRH/GHRP-2 (triple stimulus) to modulate GH secretion. Deconvolution-estimated basal and pulsatile GH secretion was assessed. Administration of Te/placebo elevated Te by 2.8-fold, DHT by 2.6-fold, and E(2) concentrations by 1.9-fold above placebo/placebo. Te/dutasteride and Te/anastrozole reduced stimulated DHT and E(2) by 89 and 86%, respectively. Stepwise forward-selection regression analysis revealed that 1) Te positively determines mean (P = 0.017) and peak (P < 0.001) GH concentrations, basal GH secretion (P = 0.015), and pulsatile GH secretion stimulated by GHRP-2 (P < 0.001); 2) Te and E(2) jointly predict GH responses to the triple stimulus (positively for Te, P = 0.006, and negatively for E(2), P = 0.031); and 3) DHT correlates positively with pulsatile GH secretion during SS infusion (P = 0.011). These effects persisted when abdominal visceral fat was included in the regression. The present outcomes suggest a tetrapartite model of GH regulation in men, in which systemic concentrations of Te, DHT, and E(2) along with abdominal visceral fat determine the selective actions of GH secretagogues and SS.
Study Information
pubmed
2008
2008-12-16T00:00:00.000Z
10.1210/jc.2008-2108
45
58