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  • 1
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    Effects of Recombinant Human Insulin-Like Growth Factor I Administration on Growth Hormone (GH) Secretion, Both Spontaneous and Stimulated by GH-Releasing Hormone or Hexarelin, a Peptidyl GH Secretagogue, in Humans1
    The Endocrine Society ; 1999
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 1 ( 1999-01-01), p. 285-290
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 84, No. 1 ( 1999-01-01), p. 285-290
    Abstract: The negative feedback exerted by insulin-like growth factor I (IGF-I) on GH secretion occurs at the pituitary, as well as the hypothalamic level, via stimulation of SS and/or inhibition of GHRH release. In fact, recombinant human IGF-I (rhIGF-I) administration inhibits basal GH secretion, at least in fasted humans, though its effect on the GH response to GHRH is still controversial. GH secretagogues (GHS) are peptidyl and nonpeptidyl molecules that act on specific receptors at the pituitary and/or the hypothalamic level. Contrary to GHRH, the GH-releasing activity of GHS is strong, reproducible, and even partially refractory to inhibitory influences such as exogenous somatostatin. We studied the effects of rhIGF-I administration (20μ g/kg sc at 0 min) on GH secretion, either spontaneous or stimulated by GHRH (2 μg/kg iv at +180 min) or Hexarelin (HEX, 2.0 μg/kg iv at+ 180 min), a GHS, in eight normal young women (age, mean ± sem, 28.3 ± 1.2 yr; body mass index, 20.1± 0.5 kg/m2). rhIGF-I administration increased IGF-I levels (peak vs. baseline: 420.3 ± 30.5 vs. 274.4 ± 25.3 μg/L, P & lt; 0.05) within the physiological range from +120 to +300 min. No variation in glucose or insulin levels was recorded. rhIGF-I did not reduce spontaneous GH secretion [areas under curves (AUC)0–300 min 140.6± 66.3 vs. 114.6 ± 32.1 μg/L·h], whereas it inhibited the GH response to both GHRH (AUC180–300 min 447.7 ± 159.4 vs. 715.9 ± 104.3 μg/L·h, P & lt; 0.05) and HEX (620.3 ± 110.4 vs. 1705.9 ± 328.9 μg/L·h, P & lt; 0.03). The percent inhibitory effect of rhIGF-I on the GH response to GHRH (41.7 ± 12.8%) was lower than that on the response to HEX (57.7 ± 11.0%). In fact, the GH response to GHRH alone was clearly lower than that to HEX alone (P & lt; 0.05), whereas the GH responses to GHRH and HEX were similar after rhIGF-I. Our findings show that the sc administration of low rhIGF-I doses inhibits the GH response to GHRH and, even more, that to HEX; whereas, at least in this experimental design in fed conditions, it does not modify the spontaneous GH secretion. Because GHS generally show partial refractoriness to inhibitory inputs, including exogenous somatostatin, the present results point toward a peculiar sensitivity of GHS to the negative feedback action of IGF-I.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/jcem.84.1.5386
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 1999
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  • 2
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    Reduction of the somatotrope responsiveness to GHRH and Hexarelin but not to arginine plus GHRH in hyperprolactinemic patients
    Springer Science and Business Media LLC ; 1997
    In:  Journal of Endocrinological Investigation Vol. 20, No. 10 ( 1997-11), p. 597-602
    Details
    In: Journal of Endocrinological Investigation, Springer Science and Business Media LLC, Vol. 20, No. 10 ( 1997-11), p. 597-602
    Type of Medium: Online Resource
    ISSN: 0391-4097 , 1720-8386
    URL: Article
    DOI: 10.1007/BF03346916
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1997
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    detail.hit.zdb_id: 432272-1
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  • 3
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    The GH, prolactin, ACTH and cortisol responses to Hexarelin, a synthetic hexapeptide, undergo different age-related variations
    Oxford University Press (OUP) ; 1997
    In:  European Journal of Endocrinology ( 1997-12-1), p. 635-642
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), ( 1997-12-1), p. 635-642
    Abstract: Hexarelin (HEX) is a synthetic growth hormone-releasing peptide (GHRP) which acts on specific receptors at both the pituitary and the hypothalamic level to stimulate GH release in an age-dependent manner. Like other GHRPs, HEX possesses also prolactin (PRL) and ACTH/cortisol-releasing activity. similar to that of human corticotropin-releasing hormone (hCRH). The mechanisms underlying the stimulatory effect of GHRPs on lactotrope and corticotrope secretion are even less clear and the influence of age on these endocrine activities of GHRPs is unknown. To clarify this point we studied the GH, PRL, ACTH and cortisol responses to the maximal effective dose of HEX (2.0 micrograms/kg i.v.) in: 12 prepubertal children (Pre-C, 8 male, 4 female, age 5.8-12.1 years); 12 pubertal normal short children (Pub-C, 5 male, 7 female, age 9.7-15.5 years, pubertal stage II-IV); 20 normal young adults (Young, 6 males, 14 females, age 23-32 years); and in 16 normal elderly people (Elderly, 5 male, 11 female, age 66-81 years). The GH response to HEX was clear in Pre-C (0-120 min area under curve, mean +/- S.E.M. 769.5 +/- 122.2 micrograms*min/l) but strikingly increased (P 〈 0.001) in Pub-C (1960.2 +/- 283.5 micrograms*min/l). The HEX-induced GH rise in Young (1829.7 +/- 243.1 micrograms*min/l) persisted similar to that in Pub-C, but decreased in Elderly (951.1 +/- 232.9 micrograms*min/I, P 〈 0.005); the latter was, in turn, similar to that in Pre-C. HEX induced a significant PRL increase which, however, showed no age-related variations, being similar in Pre-C (512.1 +/- 88.0 micrograms*min/l), Pub-C (584.0 +/- 106.0 micrograms*min/l), Young (554.9 +/- 56.0 micrograms*min/l) and Elderly (523.9 +/- 59.6 micrograms*min/l). The ACTH-releasing activity of HEX was present in Pre-C (1356.6 +/- 204.9 pg*min/ml) and was clearly enhanced (P 〈 0.02) in Pub-C (2253.5 +/- 242.8 pg*min/ml). The ACTH rise after HEX in Young (1258.1 +/- 141.2pg*min/ml) was lower (P 〈 0.02) than that in Pub-C and similar to that in Pre-C, while the ACTH response to HEX in Elderly (1786.5 +/- 340.1 pg*min/ml) showed a further trend toward increase, being similar to that in Pub-C. On the other hand, the cortisol response to HEX showed no significant age-related variations, being not different in Pre-C (7747.2 +/- 1031.6 micrograms*min/l), Pub-C (6106.0 +/- 862.9 micrograms*min/l), Young (6827.5 +/- 509.6 micrograms*min/I) and Elderly (7950.6 +/- 658.3 micrograms*min/l). In conclusion, our present data demonstrate that in humans the GH- and ACTH-releasing activities of HEX undergo different age-related variations, while its PRL-releasing activity is not dependent on age. These finding suggest that actions at different levels and/or on different receptor subtypes mediate the different age-related hormonal effects of GHRPs.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/eje.0.1370635
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 1997
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  • 4
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    Hexarelin, a synthetic GH-releasing peptide, is a powerful stimulus of GH secretion in pubertal children and in adults but not in prepubertal children and in elderly subjects
    Springer Science and Business Media LLC ; 1998
    In:  Journal of Endocrinological Investigation Vol. 21, No. 8 ( 1998-9), p. 494-500
    Details
    In: Journal of Endocrinological Investigation, Springer Science and Business Media LLC, Vol. 21, No. 8 ( 1998-9), p. 494-500
    Type of Medium: Online Resource
    ISSN: 0391-4097 , 1720-8386
    URL: Article
    DOI: 10.1007/BF03347334
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1998
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    detail.hit.zdb_id: 432272-1
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  • 5
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    Low IGF-I levels are often uncoupled with elevated GH levels in catabolic conditions
    Springer Science and Business Media LLC ; 1998
    In:  Journal of Endocrinological Investigation Vol. 21, No. 2 ( 1998-2), p. 115-121
    Details
    In: Journal of Endocrinological Investigation, Springer Science and Business Media LLC, Vol. 21, No. 2 ( 1998-2), p. 115-121
    Type of Medium: Online Resource
    ISSN: 0391-4097 , 1720-8386
    URL: Article
    DOI: 10.1007/BF03350325
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1998
    detail.hit.zdb_id: 2119482-8
    detail.hit.zdb_id: 432272-1
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  • 6
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    Further Evidence of Cholinergic Impairment of the Neuroendocrine Control of the GH Secretion in Down’s Syndrome
    S. Karger AG ; 1998
    In:  Dementia and Geriatric Cognitive Disorders Vol. 9, No. 2 ( 1998), p. 78-81
    Details
    In: Dementia and Geriatric Cognitive Disorders, S. Karger AG, Vol. 9, No. 2 ( 1998), p. 78-81
    Abstract: There are data indicating that cholinergic activity is precociously impaired in Down’s syndrome (DS). On the other hand, acetylcholine as well as arginine (ARG) play a major stimulatory role in the neural control of growth hormone (GH) secretion in humans, likely acting via the inhibition of hypothalamic somatostatin release. The aim of the present study was to verify the effects of pyridostigmine (PD, 120 mg p.o.), a cholinesterase inhibitor, and ARG (0.5 g/kg i.v.) on the growth hormone-releasing hormone (GHRH) (1 µg/kg i.v.)-induced GH rise in 15 adult patients with DS (M/F: 8/7; age 26.5 ± 2.2 years; body mass index, BMI: 25.7 ± 1.0 kg/m 〈 sup 〉 2 〈 /sup 〉 ) in which the potentiating effect of PD on GH secretion has been reported to be reduced. The results in DS were compared to those in 15 normal subjects (NS) (M/F: 8/7; age: 30.0 ± 1.3 years; BMI: 21.4 ± 0.4 kg/m 〈 sup 〉 2 〈 /sup 〉 ). Basal GH and insulin growth factor I (IGF-1) levels in DS (1.8 ± 0.7 and 206.5 ± 21.0 µg/l) were similar to those in NS (1.4 ± 0.3 and 179.4 ± 11.0 µg/l). The GH response to GHRH alone in DS (526.5 ± 120.1 µg/l/h) was lower (p 〈 0.05) than that recorded in NS (895.4 ± 153.7 µg/l/h). The GHRH-induced GH rise was potentiated by PD both in DS (1,138 ± 184.2 µg/l/h; p 〈 0.02 vs. GHRH alone) and in NS (2,213.8 ± 212.8 µg/l/h; p 〈 0.005 vs. GHRH alone); however, as the percent potentiating effect of PD was similar in both groups (215 and 247%, respectively) the GH response to GHRH+PD in DS was lower (p 〈 0.005) than that in NS. The GHRH-induced GH rise was also potentiated by ARG in both DS (2,243 ± 362.4 µg/h; p 〈 0.001 vs. GHRH alone) and NS (2,764.3 ± 325.7 µg/l/h; p 〈 0.005 vs. GHRH alone). As the percent potentiating effect of ARG in DS was more marked than in NS (425 vs. 308%, respectively), the GH response to GHRH+ARG became similar in both groups. No sex-related difference was found in the GH response to various stimuli both in DS and NS. In conclusion, these data demonstrate that the potentiating effect of PD but not that of ARG is impaired in adults with DS in whom a reduced somatotrope responsiveness to GHRH is present. These findings indicate that in DS the pituitary GH releasable pool is fully preserved while an impairment of the tuberoinfundibular cholinergic pathways could lead to somatostatinergic hyperactivity and low somatotrope responsiveness to GHRH.
    Type of Medium: Online Resource
    ISSN: 1420-8008 , 1421-9824
    URL: Article
    DOI: 10.1159/000017027
    Language: English
    Publisher: S. Karger AG
    Publication Date: 1998
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  • 7
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    Hexarelin, a synthetic growth hormone releasing peptide, stimulates prolactin secretion in acromegalic but not in hyperprolactinaemic patients
    Wiley ; 1996
    In:  Clinical Endocrinology Vol. 44, No. 1 ( 1996-01), p. 67-71
    Details
    In: Clinical Endocrinology, Wiley, Vol. 44, No. 1 ( 1996-01), p. 67-71
    Abstract: OBJECTIVE In man, new synthetic peptides such as hexarelin have been shown to have a potent and dose dependent GH releasing activity. Furthermore, a significant PRL releasing activity has also been demonstrated, but this has been investigated in less detail. We have therefore evaluated the effect of hexarelin on PRL and GH secretion in patients with active acromegaly or pathological hyperprolactinaemia. DESIGN Hexarelin (2 μg/kg i.v.), a modified derivative of GHRP‐6 of the following structure: His‐2‐Me‐ D ‐Trp‐Ala‐Trp‐ D ‐Phe‐Lys‐NH 2 , or placebo, was administered in random order on two separate occasions. PATIENTS Eight patients with active acromegaly (ACRO, 6 F and 2 M, mean age 61.7 years, range 56–73), 6 with macroadenomas and 2 without radiological signs of tumour, and 6 female patients with pathological hyperprolactinaemia (HPRL, mean age 31.2 years, range 18–47) 5 with microadenomas and 1 with empty sella, were studied. Fourteen normal subjects (NS, 8 F and 6 M, 27.1 years, 24–30) were studied as controls. MEASUREMENTS GH and PRL levels were evaluated every 15 minutes for 2 hours after hexarelin or placebo. Both hormones were measured using commercial IRMA kits. Basal IGF‐I was measured in all subjects using an RIA following acid–ethanol extraction. RESULTS Hexarelin induced a significant increase in PRL levels in NS (median, range, Δ peak HEX vs placebo: 150 (−14–402) vs 10 (−34–24) mU/l; Δ AUC HEX vs placebo: 7710 (2 100–3 2540) vs 30 (−2 566–2 040) mU min/l, P   〈  0.01) and in ACRO (190 (−10–496) vs 6 (−100–34) mU/l; 10 170 (−5 310–51 436) vs −82 (−6 030–1 410) mU min/l, P   〈  0.02), but not in HPRL (10 (−180–80) vs 50 (−100–240) mU/l; −600 (−16 996–10 140) vs −1 950 (−8 540–14 160) mU min/l). Hexarelin also induced a lower increase of GH in HPRL (60 (30–82) vs 1.8 (−0.2–2.2) mU/l; 2 853 (1 477.6–4 372.6 vs 91.6 (−160.6–174) mU min/l, P   〈  0.05) than in NS (90.8 (50.6–181) vs 0.8 (−1.2–6.8) mU/l; 6642 (2 004–13 252.6 vs 42 (456–900) mU min/l, P   〈  0.01) or in ACRO (117.2 (21.2–420.6 vs 3.8 (−2.2–18) mU/l; 6645 (1 554–22 138.6 vs 334.6 (−324–1 065) mU min/l, P   〈  0.02). CONCLUSIONS Our data show that the PRL releasing effect of hexarelin is preserved in acromegaly but lost in pathological hyperprolactinaemia. In contrast with acromegaly, the GH releasing effect of hexarelin is also blunted in hyperprolactinaemic patients. These data demonstrate that patients with pathological hyperprolactinaemia are partially refractory to the activity of hexarelin.
    Type of Medium: Online Resource
    ISSN: 0300-0664 , 1365-2265
    URL: Article
    DOI: 10.1046/j.1365-2265.1996.626446.x
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 1996
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  • 8
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    The GH-Releasing Effect of Hexarelin, a Synthetic Hexapeptide, in Newborns is Lower than in Young Adults
    Walter de Gruyter GmbH ; 1997
    In:  Journal of Pediatric Endocrinology and Metabolism Vol. 10, No. 5 ( 1997-01)
    Details
    In: Journal of Pediatric Endocrinology and Metabolism, Walter de Gruyter GmbH, Vol. 10, No. 5 ( 1997-01)
    Type of Medium: Online Resource
    ISSN: 2191-0251 , 0334-018X
    URL: Article
    DOI: 10.1515/JPEM.1997.10.5.491
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 1997
    detail.hit.zdb_id: 1231070-0
    detail.hit.zdb_id: 2583847-7
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  • 9
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    Repeated Administration of Growth Hormone-Releasing Hormone With or Without Previous Administration of Pyridostigmine in Insulin-Dependent Diabetes Mellitus
    Georg Thieme Verlag KG ; 1997
    In:  Hormone and Metabolic Research Vol. 29, No. 04 ( 1997-4), p. 180-183
    Details
    In: Hormone and Metabolic Research, Georg Thieme Verlag KG, Vol. 29, No. 04 ( 1997-4), p. 180-183
    Type of Medium: Online Resource
    ISSN: 0018-5043 , 1439-4286
    URL: Article
    DOI: 10.1055/s-2007-979017
    RVK:
    XA 46918
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 1997
    detail.hit.zdb_id: 2056576-8
    detail.hit.zdb_id: 80125-2
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  • 10
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    Low Dose Hexarelin and Growth Hormone (GH)-Releasing Hormone as a Diagnostic Tool for the Diagnosis of GH Deficiency in Adults: Comparison with Insulin-Induced Hypoglycemia Test1
    The Endocrine Society ; 1999
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 8 ( 1999-08-01), p. 2633-2637
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 84, No. 8 ( 1999-08-01), p. 2633-2637
    Abstract: GH deficiency (GHD) in adults must be shown by provocative testing of GH secretion. Insulin-induced hypoglycemia (ITT) is the test of choice, and severe GHD, treated with recombinant human GH replacement, is defined by a GH peak response to ITT of less than 3 μg/L. GHRH plus arginine (ARG) is a more provocative test and is as sensitive as ITT provided that appropriate cut-off limits are assumed. GH secretagogues are a family of peptidyl and nonpeptidyl GH-releasing molecules that strongly stimulate GH secretion and, even at low doses, truly synergize with GHRH. Our aim was to verify the diagnostic reliability of the hexarelin (HEX; 0.25 μg/kg, iv) and GHRH (1 μg/kg, iv) test for the diagnosis of adult GHD. To this goal, in the present study we 1) defined the normal ranges of the GH response to GHRH+HEX in a group of normal young adult volunteers (NS; n = 25; 18 men and 7 women; age, 28.5 ± 0.6 yr) and in 11 of them verified its reproducibility in a second session, and 2) compared the GH response to GHRH+HEX with that to ITT in a group of normal subjects (n = 33; 12 men and 21 women; age, 34.1 ± 1.5 yr) and hypopituitaric adults with GHD (n = 19; 10 men and 9 women; age, 39.9 ± 2.2 yr; GH peak & lt;5 μg/L after ITT). The GH response to GHRH+ARG was also evaluated in all GHD and in 77 normal subjects (40 men and 37 women; age, 28.1 ± 0.6 yr). The mean GH peak after GHRH+HEX in NS was 83.6 ± 4.5 μg/L; the third and first percentile limits of the normal GH response were 55.5 and 51.2 μg/L, respectively). The GH response to GHRH+HEX in NS showed good intraindividual reproducibility. In GHD the mean GH peak after GHRH+HEX (2.6 ± 0.7 μg/L) was similar to that after GHRH+ARG (3.6 ± 1.0 μg/L), and both were higher (P & lt; 0.001) than that after ITT (0.6± 0.1 μg/L); the GH responses to GHRH+HEX were positively associated with those to ITT and GHRH+ARG. Analyzing individual GH responses, 100% had severe GHD after ITT (GH peak, & lt;3 μg/L). After GHRH+HEX all GHD had GH peaks below the third percentile limit of normality appropriate for this test (i.e. 55.5 μg/L). Thirteen of 19 (68.4%) GHD subjects had GH peaks below 3 μg/L after GHRH+HEX but all 19 (100%) had GH peaks below the first percentile limit of normality (i.e. 51.2 μg/L). The GH responses to GHRH+HEX were highly concordant with those after GHRH+ARG. In conclusion, the present results define normal limits of the GH response to stimulation with low dose HEX+GHRH in normal adults and show that this test is as sensitive as ITT for the diagnosis of adult GHD provided that appropriate cut-off limits are considered.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/jcem.84.8.5904
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 1999
    detail.hit.zdb_id: 2026217-6
    detail.hit.zdb_id: 3029-6
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