Determinants of GH-releasing hormone and GH-releasing peptide synergy in men.

[dragonfire101]

So Dat given various determinants may vary results of using GHRP & GHRH


Am J Physiol Endocrinol Metab. 2009 May;296(5):E1085-92. Epub 2009 Feb 24.
Determinants of GH-releasing hormone and GH-releasing peptide synergy in men.

Veldhuis JD, Bowers CY.

Mayo School of Graduate Medical Education, Mayo Clinic, Rochester, MN 55905, USA. [email protected]

Age, sex steroids, and abdominal-visceral fat (AVF) jointly affect pulsatile growth hormone (GH) secretion. Pulsatile GH secretion in turn is controlled by GH-releasing hormone (GHRH), GH-releasing peptide (GHRP), and somatostatin. Marked stimulation of pulsatile GH secretion is achieved via GHRH-GHRP synergy. Nonetheless, how key modulators of GH secretion, such as age, sex steroids, and body mass index, modify GHRH-GHRP synergy is not known. The present strategy was to 1) infuse GHRH and GHRP-2 simultaneously to evoke synergy and 2) downregulate the gonadal axis with leuprolide and then restore placebo (Pl) or testosterone (T) to clamp the sex steroid milieu. Forty-seven men [18-74 yr of age, T = 7-1,950 ng/dl, estradiol (E(2)) = 5-79 pg/ml, insulin-like growth factor (IGF)-I = 115-817 microg/l, AVF = 11-349 cm(2)] were studied. GHRH-GHRP synergy correlated negatively with age and AVF (both P < 0.001) and positively with IGF-I (P < 0.001) and IGF-binding protein (IGFBP)-3 (P = 0.031). Unstimulated basal (nonpulsatile) GH secretion correlated positively with T (P = 0.015) and E(2) (P = 0.004) concentrations. Fasting pulsatile GH secretion varied negatively with age (P = 0.017) and positively with IGF-I (P = 0.002) and IGFBP-3 (P = 0.001). By stepwise forward-selection multivariate analyses, AVF, IGF-I, and IGFBP-3 together explained 60% of the variability in GHRH-GHRP synergy (P < 0.001), E(2) accounted for 17% of the variability in basal GH secretion (P = 0.007), and IGF-I explained 20% of the variability in fasting pulsatile GH secretion (P = 0.002). In conclusion, a paradigm examining GHRH-GHRP synergy under a sex steroid clamp reveals highly selective control of basal, pulsatile, and synergistic peptide-driven GH secretion by AVF, E(2), and IGF-I in healthy men.


J Clin Endocrinol Metab. 2009 Jun;94(6):2137-43. Epub 2009 Apr 7.
Novel relationships of age, visceral adiposity, insulin-like growth factor (IGF)-I and IGF binding protein concentrations to growth hormone (GH) releasing-hormone and GH releasing-peptide efficacies in men during experimental hypogonadal clamp.

Veldhuis JD, Keenan DM, Bailey JN, Adeniji AM, Miles JM, Bowers CY.

Endocrine Research Unit, Mayo School of Graduate Medical Education, Clinical Translational Science Center, Mayo Clinic, Rochester, Minnesota 55905, USA. [email protected]

BACKGROUND: Sex steroids influence GH secretion in complex ways. HYPOTHESIS: Analyses in a low sex-steroid milieu will help unveil the effects of age and other nonsteroidal regulators on GH secretion. CONTEXT: The study was conducted in a tertiary medical center. Subjects: The study group included 13 healthy young men and 12 healthy older men. METHODS: We used GnRH agonist-induced down-regulation of testosterone and estradiol secretion, followed by consecutive infusion of l-arginine and GHRH or GHRP-2, to test secretagogue efficacies. OUTCOMES: We measured basal and pulsatile GH secretion. RESULTS: During experimental testosterone/estradiol deprivation, older (57 +/- 1.7 yr) men maintained: 1) 6.8-fold less pulsatile GH secretion (P < 0.001); and 2) 2-fold lower maximal GH responses to GHRH (P = 0.0065) and GHRP-2 (P = 0.022) than young (23 +/- 1.1 yr old) individuals. Stepwise forward-selection regression analyses identified: 1) abdominal visceral fat as a dominant negative predictor of both GHRH (R(2) = 0.49; P = 0.001) and GHRP-2 (R(2) = 0.38; P = 0.005) efficacies; and 2) fasting IGF-I concentration as a major positive correlate of GHRH (R(2) = 0.52; P < 0.001) and GHRP-2 (R(2) = 0.31; P = 0.018) efficacies. Unstimulated pulsatile GH secretion was jointly correlated with IGF-I and IGFBP-3 (P = 0.039). CONCLUSION: Measures of body composition (abdominal visceral fat) and pulsatile GH action (IGF-I) explain up to one half of interindividual variability in the efficacies of GHRH and GHRP-2 in sex steroid-depleted men. Accordingly, normative ranges for maximal single peptide-stimulated GH secretion in short-term hypogonadal states should incorporate the influence of these determinants as well as age.

 

[DatBtrue]

You are a member of my private forum... but I'll cut and paste for you.

You said "So Dat given various determinants may vary results of using GHRP & GHRH"?

Yes the GH release result will vary between people. Being fat is a negative...age will play a part as well as sex and then the hormonal environment one finds one's self in can all play a part.

Someone posted a study on my board Testosterone inhibition of growth hormone release stimulated by a growth hormone secretagogue: studies in the rat and dog, Rigamonti and I responded as follows:

The following 2009 study was authored by two of the giants in this fields, Johannes D. Veldhuis and Cyril Y. Bowers.

Aromatase and 5-Reductase Inhibition during an Exogenous Testosterone Clamp Unveils Selective Sex Steroid Modulation of Somatostatin and Growth Hormone Secretagogue Actions in Healthy Older Men, Johannes D. Veldhuis, Kristi L. Mielke, Mihaela Cosma, Cacia Soares-Welch, Remberto Paulo, John M. Miles and Cyril Y. Bowers, The Journal of Clinical Endocrinology & Metabolism Vol. 94, No. 3 973-981 2009


Background: How endogenous testosterone (Te), 5-dihydrotestosterone (DHT), and estradiol (E2) regulate pulsatile GH secretion is not understood.

Hypothesis: Conversion of Te to androgenic (Te->DHT) or estrogenic (Te->E2) products directs GH secretion.

Subjects and Location: Healthy older men (N = 42, ages 50–79 yr) participated at an academic medical center.

Methods: We inhibited 5-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.

Endpoints: Deconvolution-estimated basal and pulsatile GH secretion was assessed.

Results: Administration of Te/placebo elevated Te by 2.8-fold, DHT by 2.6-fold, and E2 concentrations by 1.9-fold above placebo/placebo. Te/dutasteride and Te/anastrozole reduced stimulated DHT and E2 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 E2 jointly predict GH responses to the triple stimulus (positively for Te, P = 0.006, and negatively for E2, 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.

Conclusion: The present outcomes suggest a tetrapartite model of GH regulation in men, in which systemic concentrations of Te, DHT, and E2 along with abdominal visceral fat determine the selective actions of GH secretagogues and SS.​

So injecting testosterone and measuring GH is not very valuable.

In the study I posted note that administration of Te elevated Te by 2.8-fold, DHT by 2.6-fold, and E2 concentrations by 1.9-fold above placebo/placebo.

That GH responses are positive to Te and negative to E2. That DHT correlates positively with pulsatile GH secretion during SS infusion.

There are three hormones that testosterone injection will increase. Each with a distinct effect on GH.

To change the mix of hormones the study noted, that Te/dutasteride and Te/anastrozole reduced stimulated DHT and E2 by 89 and 86%, respectively.

This sort of study is far more instructive then the one you posted (Rigamonti). Your study starts with "Anabolic steroids are frequently taken by athletes and bodybuilders..." so I am sad to say that type of phrasing has revealed to me throughout the years to be on guard when I read the study.

The study I posted could lead one to understand that testosterone w/ an AI such as anastrozole to reduce the negative influence of E2 would have a positive effect on GH and that the rise in DHT would help in the formation of
pulsatile release.