GH Shutdown - Mechanisms

J Clin Endocrinol Metab. 2003 Nov;88(11):5221-6.

High dose growth hormone exerts an anabolic effect at rest and during exercise in endurance-trained athletes.

Healy ML, Gibney J, Russell-Jones DL, Pentecost C, Croos P, Sönksen PH, Umpleby AM.

------------------ Baseline --------- 1Wk-----------4 Wk--------- <>Placebo-

IGF-I (nmol/liter) 24.6 ± 3.0 / 89.6 ± 12.21/ 106.3 ± 16.41<> 25.8 ± 2.7-- 25.4 ± 2.7-- 25.2 ± 2.6

ft3 (pmol/liter) 5.1 ± 0.3 6.0 ± 0.12 6.1 ± 0.22 4.8 ± 0.2 4.9 ± 0.2 4.8 ± 0.1

fT4 (pmol/liter) 15.5 ± 1.5 11.5 ± 1.02 10.6 ± 0.92 15.8 ± 1.6 15.6 ± 1.7 15.8 ± 1.5

Testosterone(nmol/liter) 18.3 ± 3.2 18.5 ± 3.4 18.5 ± 3.3 16.7 ± 2.6 16.3 ± 2.6 16.4 ± 2.2

Glucose (mmol/liter) 4.7 ± 0.3 5.5 ± 0.5 5.3 ± 0.2 4.5 ± 0.4 4.2 ± 0.2 4.4 ± 0.3

Insulin (mU/liter) 7.9 ± 1.6 22.6 ± 3.92 16.0 ± 9.32 6.0 ± 0.3 5.6 ± 1.9 9.3 ± 2.4

HOMA IR 1.4 ± 0.2 5.1 ± 1.02 3.3 ± 0.62 1.1 ± 0.4 1.0 ± 0.3 1.6 ± 0.5

Total cholesterol (mmol/liter) 4.3 ± 0.3 4.0 ± 0.5 4.1 ± 0.3 3.4 ± 0.3 3.3 ± 0.3 3.5 ± 0.6

Triglyceride 1.1 ± 0.2 2.0 ± 0.5 1.3 ± 0.1 0.6 ± 0.1 0.7 ± 0.1 0.5 ± 0.1

LDL cholesterol (mmol/liter) 2.6 ± 0.3 2.2 ± 0.3 2.3 ± 0.3 1.6 ± 0.4 1.6 ± 0.3 1.6 ± 0.5

HDL cholesterol (mmol/liter) 1.2 ± 0.1 1.0 ± 0.1 1.1 ± 0.1 1.5 ± 0.1 1.5 ± 0.1 1.7 ± 0.2

Body weight (kg) 74.4 ± 1.1 76.5 ± 1.72 77.9 ± 1.62 74.9 ± 3.4 74.9 ± 3.4 74.7 ± 3.3

Lean body mass (kg) 57.6 ± 1.1 61.0 ± 1.22 61.6 ± 2.5 61.8 ± 2.4

Total body fat (kg) 11.4 ± 1.4 11.6 ± 1.7 9.8 ± 1.9 10.1 ± 2.0

Trunk fat (kg) 4.7 ± 0.7 4.5 ± 0.9 2.8 ± 0.9 2.8 ± 0.9

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Reichlin S.

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Hindmarsh PC, Matthews DR, Brain CE, Pringle PJ, di Silvio L, Kurtz AB, Brook CG.

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VanKalpaL, Thorner MO.

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Berelowitz M, Szabo M, Frohman LA, Firestone S, Chu L, Hintz RL.

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Yamashita S, Melmed S.

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Tannenbaum GS, Ling N.

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Insulin-like growth factor I disparately regulates prolactin and growth hormone synthesis and secretion: studies using the teleost pituitary model.

Fruchtman S, Jackson L, Borski R.

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Fruchtman S, McVey DC, Borski RJ.

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Fruchtman S, Gift B, Howes B, Borski R.

Gen Comp Endocrinol. 2002 Jul;127(3):223-31.

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Kajimura S, Uchida K, Yada T, Hirano T, Aida K, Gordon Grau E.

Domest Anim Endocrinol. 2004 Apr;26(3):177-88.

Rapid suppressing action of insulin-like growth factor-I (IGF-I) on GH release from anterior pituitary cells of goats.

Katoh K, Shimoguchi R, Ishiwata H, Obara Y.

.

Eur J Endocrinol. 2007 Jun;156(6):647-53.

Pharmacokinetics and pharmacodynamics of GH: dependence on route and dosage of administration.

Keller A, Wu Z, Kratzsch J, Keller E, Blum WF, Kniess A, Preiss R, Teichert J, Strasburger CJ, Bidlingmaier M.

Hospital for Children and Adolescents, University of Leipzig, Oststr. 21-25, D-04317 Leipzig, Germany.

OBJECTIVE: Pharmacokinetic and pharmacodynamic data after recombinant human GH (rhGH) administration in adults are scarce, but necessary to optimize replaKalpaent therapy and to detect doping. We examined pharmacokinetics, pharmacodynamics, and 20 kDa GH after injection of rhGH at different doses and routes of administration. DESIGN: Open-label crossover study with single boluses of rhGH. METHODS: Healthy trained subjects (10 males, 10 females) received bolus injections of rhGH on three occasions: 0.033 mg/kg s.c., 0.083 mg/kg s.c., and 0.033 mg/kg i.m. Concentrations of 22 and 20 kDa GH, IGF-I, and IGF-binding proteins (IGFBP)-3 were measured repeatedly before and up to 36 h after injection. RESULTS: Serum GH maximal concentration (C(max)) and area under the time-concentration curve (AUC) were higher after i.m. than s.c. administration of 0.033 mg/kg (C(max) 35.5 and 12.0 mu g/l; AUC 196.2 and 123.8). C(max) and AUC were higher in males than in females (P < 0.01) and pharmacodynamic changes were more pronounced. IGFBP-3 concentrations showed no dose dependency. In response to rhGH administration, 20 kDa GH decreased in females and remained suppressed for 14-18 h (low dose) and 30 h (high dose). In males, 20 kDa GH was undetectable at baseline and throughout the study. CONCLUSIONS: After rhGH administration, pharmacokinetic parameters are mainly influenced by route of administration, whereas pharmacodynamic variables and 20 kDa GH concentrations are determined mainly by gender. These differences need to be considered for therapeutic use and for detection of rhGH doping.