GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Adrenocorticotrophic hormone (ACTH) responsiveness to ghrelin increases after 6 months of ketoconazole use in patients with Cushing's disease: comparison with GH-releasing peptide-6 (GHRP-6).
Correa-Silva. Silvia R SR; Nascif. Sérgio O SO; Molica. Patrícia P; Sá. Larissa B P C LB; Vieira. José G H JG; Lengyel. Ana-Maria J AM
Key Findings
- Ketoconazole markedly reduced urinary and serum cortisol over 3‑6 months.
- Basal ACTH levels rose during ketoconazole therapy, likely as suppressed corticotrophs re‑activated.
- Ghrelin‑induced ACTH responses increased significantly after 6 months of ketoconazole; GHRP‑6‑induced ACTH rose modestly and was not statistically significant.
Practical Outcomes
- For biohackers or healthy individuals, the study offers little direct guidance on using GHRP‑6. It suggests that in a disease state with excess cortisol, reducing cortisol can change how the pituitary responds to ghrelin and possibly GHRP‑6, but the findings don’t translate into actionable dosing or protocol changes for normal users.
Summary
In people with Cushing's disease, taking the drug ketoconazole for six months lowered their cortisol levels and made their bodies release more ACTH hormone at rest. When they were given ghrelin, ACTH spikes were bigger after treatment, while the boost from GHRP‑6 grew a little but not enough to be statistically clear.
Abstract
In Cushing's disease (CD), adrenocorticotrophic hormone (ACTH)/cortisol responses to growth hormone secretagogues (GHS), such as ghrelin and GHRP-6, are exaggerated. The effect of clinical treatment of hypercortisolism with ketoconazole on ACTH secretion in CD is controversial. There are no studies evaluating ACTH/cortisol responses to GHS after prolonged ketoconazole use in these patients. To compare ghrelin- and GHRP-6-induced ACTH/cortisol release before and after ketoconazole treatment in patients with CD. Eight untreated patients with CD (BMI: 28.5 +/- 0.8 kg/m(2)) were evaluated before and after 3 and 6 months of ketoconazole treatment and compared with 11 controls (BMI: 25.0 +/- 0.8). After ketoconazole use, mean urinary free cortisol values decreased significantly (before: 613.6 +/- 95.2 nmol/24 h; 3rd month: 170.0 +/- 27.9; 6th month: 107.9 +/- 30.1). The same was observed with basal serum cortisol (before: 612.5 +/- 69.0 nmol/l; 3rd month: 463.5 +/- 44.1; 6th month: 402.8 +/- 44.1) and ghrelin- and GHRP-6-stimulated peak cortisol levels (before: 1183.6 +/- 137.9 and 1045.7 +/- 132.4; 3rd month: 637.3 +/- 69.0 and 767.0 +/- 91.0; 6th month: 689.8 +/- 74.5 and 571.1 +/- 71.7 respectively). An increase in basal ACTH (before: 11.2 +/- 1.6 pmol/l; 6th month: 19.4 +/- 2.7) and in ghrelin-stimulated peak ACTH values occurred after 6 months (before: 59.8 +/- 15.4; 6th month: 112.0 +/- 11.2). GHRP-6-induced ACTH release also increased (before: 60.7 +/- 17.2; 6th month: 78.5 +/- 12.1), although not significantly. The rise in basal ACTH levels during ketoconazole treatment in CD could be because of the activation of normal corticotrophs, which were earlier suppressed by hypercortisolism. The enhanced ACTH responses to ghrelin after ketoconazole in CD could also be due to activation of the hypothalamic-pituitary-adrenal axis and/or to an increase in GHS-receptors expression in the corticotroph adenoma, consequent to reductions in circulating glucocorticoids.
Study Information
pubmed
2009
2009-04-29T00:00:00.000Z
10.1111/j.1365-2265.2009.03618.x
7
30