Intravenous administration of recombinant IGF-I lowers serum GHRH and TSH

Laron, Zvi; Klinger, B.; Silbergeld, A.; Lewin, Ruben F.; Erster, B.; Gil-Ad, Irit

doi:10.1530/acta.0.1230378

Cited by 48 publications

(33 citation statements)

References 12 publications

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“…In humans, the inhibitory effect of rhIGF-I on somatotroph hypersecretion has been shown in Laron's syndrome, IDDM, malnutrition, and fasting (7,8,10,24,25). In healthy women, a low rhIGF-I dose inhibited the GHRH-and, more markedly, the GHRP-induced (but not the spontaneous) GH secretion (13).…”

Section: Discussionmentioning

confidence: 98%

“…GH hypersecretion in AN would rest on the reduction of the negative IGF-I feedback mechanism (19,(21)(22)(23), as also implied by evidence that recombinant human (rh)IGF-I, administered to subjects with GH hypersecretion, inhibits the secretion of GH (7,8,10,24,25).…”

mentioning

confidence: 95%

“…Moreover, the increased IGFBP-1 levels might curtail the negative IGF-I feedback in AN. I NSULIN-LIKE growth factor (IGF)-I exerts an inhibitory feedback action on GH secretion both in animals and in humans (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). The negative IGF-I feedback may occur directly at the pituitary, through activation of the IGF-I receptor, leading to inhibition of GH synthesis and release (1)(2)(3)(4)(5).…”

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confidence: 99%

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Effects of Recombinant Human Insulin-Like Growth Factor I Administration on Spontaneous and Growth Hormone (GH)-Releasing Hormone-Stimulated GH Secretion in Anorexia Nervosa

Gianotti¹

2000

Journal of Clinical Endocrinology & Metabolism

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Exaggerated GH and reduced insulin-like growth factor I (IGF-I) levels are common features in anorexia nervosa (AN). A reduction of the negative IGF-I feedback could account, in part, for GH hypersecretion. To ascertain this, we studied the effects of recombinant human (rh)IGF-I on spontaneous and GH-releasing hormone (GHRH)-stimulated GH secretion in nine women with AN [body mass index, 14.1 Ϯ 0.6 kg/m 2 ] and in weight matched controls (normal weight). Mean basal GH concentrations (mGHc) and GHRH (2.0 g/kg, iv) stimulation were significantly higher in AN. rhIGF-I administration (20 g/kg, sc) significantly reduced mGHc in AN (P Ͻ 0.01), but not normal weight, and inhibited peak GH response to GHRH in both groups; mGHc and peak GH, however, persisted at a significantly higher level in AN. Insulin, glucose, and IGFBP-1 basal levels were similar in both groups. rhIGF-I inhibited insulin in AN, whereas glucose remained unaffected in both groups. IGFBP-1 increased in both groups (P Ͻ 0.05), with significantly higher levels in AN. IGFBP-3 was under basal conditions at a lower level in AN (P Ͻ 0.05) and remained unaffected by rhIGF-I. This study demonstrates that a low rhIGF-I dose inhibits, but does not normalize, spontaneous and GHRH-stimulated GH secretion in AN, pointing also to the existence of a defective hypothalamic control of GH release. Moreover, the increased IGFBP-1 levels might curtail the negative IGF-I feedback in

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 95%

mentioning

confidence: 99%

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Effects of Recombinant Human Insulin-Like Growth Factor I Administration on Spontaneous and Growth Hormone (GH)-Releasing Hormone-Stimulated GH Secretion in Anorexia Nervosa

Gianotti¹

2000

Journal of Clinical Endocrinology & Metabolism

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“…The recent availability of biosynthetic IGF-I [8] made it possible to initiate therapeutic trials with this drug administered to LTD patients who so far had suffered from an untreatable disease [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Among the biological effects induced by IGF-I was suppression of circulating (serum) hGH and TSH [10,11]. It was therefore of interest to study the influence of acute and prolonged IGF-I administration on prolactin (PRL) secretion.…”

mentioning

confidence: 99%

Serum Prolactin in Patients with Laron-Type Dwarf ism: Effect of Insulin-Like Growth Factor I

Silbergeld

Klinger²,

Schwartz³

et al. 1992

Horm Res

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Prolactin (PRL) secretion was studied in Laron-type dwarfism (LTD) patients (8 children and 9 adults) in basal condition, after acute insulin-like growth factor (IGF-I) or TRH injections and during 2 months of daily IGF-I treatment. Basal PRL was repeatedly higher (12.6 ± 1.6 µg/l) than that in control subjects (7.6 ± 1.2 µg/l, p < 0.05). Acute IGF-I injection caused an immediate slight decrease in serum PRL and growth hormone (GH), followed by a progressive rise to mean peak levels of 33.3 ± 4.5 µg/l again parallel to serum hGH which rose to 86 ± 20 µg/l – a response to the IGF-I-induced hypoglycemia. Intravenous TRH in LTD children induced a marked response in serum PRL, similar to that registered in estrogenized adult females. Serum PRL did not show consistent changes during chronic IGF-I treatment. It is suggested that the higher-than-normal PRL levels and release in LTD patients are due to a drift phenomenon of the mammosomatotropes which produce large amounts of hGH.

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Model‐Informed Dose Selection for Xentuzumab, a Dual Insulin‐Like Growth Factor‐I/II—Neutralizing Antibody

Parra-Guillén

Schmid

Janda

et al. 2019

Clin Pharma and Therapeutics

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Over the past decade, the insulin‐like growth factor (IGF)‐signaling pathway has gained substantial interest as potential therapeutic target in oncology. Xentuzumab, a humanized IgG1 monoclonal antibody, binds to IGF‐I and IGF‐II thereby inhibiting the downstream signaling essential for survival and tumor growth. This pathway is further regulated by circulating IGF binding proteins (IGFBPs). In this work, a mechanistic model characterizing the dynamics and interactions of IGFs, IGFBPs, and Xentuzumab has been developed to guide dose selection. Therefore, in vitro and in vivo literature information was combined with temporal IGF‐I, IGF‐II, and IGFBP‐3 total plasma concentrations from two phase I studies. Based on the established quantitative framework, the time‐course of free IGFs as ultimate drug targets not measured in clinics was predicted. Finally, a dose of 1000 mg/week—predicted to reduce free IGF‐I and free IGF‐II at steady‐state by at least 90% and 64%, respectively—was suggested for phase II.

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Intravenous administration of recombinant IGF-I lowers serum GHRH and TSH

Cited by 48 publications

References 12 publications

Effects of Recombinant Human Insulin-Like Growth Factor I Administration on Spontaneous and Growth Hormone (GH)-Releasing Hormone-Stimulated GH Secretion in Anorexia Nervosa

Effects of Recombinant Human Insulin-Like Growth Factor I Administration on Spontaneous and Growth Hormone (GH)-Releasing Hormone-Stimulated GH Secretion in Anorexia Nervosa

Serum Prolactin in Patients with Laron-Type Dwarf ism: Effect of Insulin-Like Growth Factor I

Model‐Informed Dose Selection for Xentuzumab, a Dual Insulin‐Like Growth Factor‐I/II—Neutralizing Antibody

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