Activity of GH/IGF-I axis in trauma and septic patients during artificial nutrition: different behavior patterns?

The aim of this study was to compare several parameters of GH/IGF-I axis activity in septic and trauma patients during Intensive Care Unit (ICU) stay. To this goal, 13 patients with sepsis (SEP) and 16 with trauma (TRA) were studied. Thirty-three adult subjects (AS) were studied as controls.

Normal IGF-I and enhanced IGFBP-3 response to very low rhGH dose in patients with dilated cardiomyopathy.

Well-nourished patients with dilated cardiomyopathy (DCM) show slight reduction of mean basal IGF-I levels which, however, display a response to a rhGH dose as low as 5.0 microg/kg/day similar to that of age-matched control subjects (CS). To further investigate peripheral GH sensitivity, we studied the IGF-I and IGFBP-3 responses to 4-day s.

Cardiac effects of hexarelin in hypopituitary adults.

Growth hormone (GH)-releasing peptides possess specific pituitary, hypothalamic, and myocardial receptors. Seven adult male patients with GH deficiency (GHD) (age, mean+/-S.E.

Growth hormone and hexarelin prevent endothelial vasodilator dysfunction in aortic rings of the hypophysectomized rat.

The endothelial vasodilation mechanism(s) has been investigated in aortic rings of hypophysectomized male rats as well as hypophysectomized rats treated for 7 days with growth hormone (GH, 400 microg/kg, s.c.) or hexarelin (80 microg/kg, s.

Activity of GH/IGF-I axis in patients with dilated cardiomyopathy.

Objective: There is evidence showing that GH and IGF-I have specific receptors in the heart and that these hormones are able to promote cardiac remodelling and inotropism. It has been reported that patients with dilated cardiomyopathy (DCM) benefit from treatment with rhGH showing a striking increase in cardiac contractility. However, until now, the activity of GH/IGF-I axis in DCM has never been clearly assessed.

Acute cardiovascular and hormonal effects of GH and hexarelin, a synthetic GH-releasing peptide, in humans.

Reduced cardiac mass and performances are present in GH deficiency and are counteracted by rhGH replacement. GH and IGF-I possess specific myocardial receptors and have been reported able to exert an acute inotropic effect. Synthetic GH secretagogues (GHS) possess specific pituitary and hypothalamic but even myocardial receptors.

Radionuclide angiocardiographic evaluation of the cardiovascular effects of recombinant human IGF-I in normal adults.

Objective: IGF-I possesses specific myocardial receptors and is able to promote cardiac remodelling and even inotropic effects in both humans and other animals. In fact, reduced cardiac mass and performance are present in GH deficiency and these alterations are counteracted by recombinant human (rh) GH replacement, restoring IGF-I levels. Recently, the acute administration of 60 microg/kg rhIGF-I has also been reported to be able to improve cardiac performance evaluated by echocardiography or impedance cardiography in normal subjects.

Specific receptors for synthetic GH secretagogues in the human brain and pituitary gland.

In vitro studies have been performed to demonstrate and characterize specific binding sites for synthetic GH secretagogues (sGHS) on membranes from pituitary gland and different human brain regions. A binding assay for sGHS was established using a peptidyl sGHS (Tyr-Ala-hexarelin) which had been radioiodinated to high specific activity at the Tyr residue. Specific binding sites for 125I-labelled Tyr-Ala-hexarelin were detected mainly in membranes isolated from pituitary gland and hypothalamus, but they were also present in other brain areas such as choroid plexus, cerebral cortex, hippocampus and medulla oblongata with no sex-related differences.

Identification of a pituitary growth hormone-releasing peptide (GHRP) receptor subtype by photoaffinity labeling.

Hexarelin, an analogue of GHRP-6, in which D-Tryptophan has been replaced by its 2-methyl derivative, is known to release growth hormone (GH) in vivo and in vitro by direct action on receptors present in anterior pituitary cells. Measurement of second messengers (c-AMP, Ca++, IP3) upon somatotrophs stimulation, suggests the existence of more than one GHRP receptor subtype. In order to document such an hypothesis, we have used a new photoactivatable derivative of Hexarelin, Tyr-Bpa-Ala-Hexarelin.

Hepatic extraction of hexarelin, a new peptidic GH secretagogue, in the isolated perfused rat liver.

Purpose: To assess the hepatic extraction of hexarelin (HEX), a novel peptidyl GH secretagogue, in the isolated perfused rat model and document the in vitro binding of HEX to plasma proteins using plasma from rats, dogs, pigs, and humans.

Methods: Rat liver was perfused in situ using a recirculating system. The recirculating perfusate consisted of a Krebs Henseleit buffer containing 20% (v/v) prewashed bovine red blood cells, 1% albumin, and lg/L dextrose.

Effects of GHRP-2 and hexarelin, two synthetic GH-releasing peptides, on GH, prolactin, ACTH and cortisol levels in man. Comparison with the effects of GHRH, TRH and hCRH.

GHRP-2 (D-Ala-D-beta Nal-Trp-D-Phe-Lys-NH2) and Hexarelin (HEX) (His-D-2-methylTrp-Ala-Trp-DPhe-Lys-NH2) are synthetic, non-natural super-analogs of GHRP-6 endowed with potent stimulatory effect on GH secretion and slight stimulatory effect on PRL, ACTH and cortisol levels. Their GH-releasing activity ahs never been compared each other and their effects on PRL, ACTH and cortisol have never been compared with that of other stimuli. To clarify these points, in 6 normal young adults (22-27 yr) we studied the GH, PRL, ACTH and cortisol responses to 1 and 2 micrograms/kg i.

Mechanisms underlying the negative growth hormone (GH) autofeedback on the GH-releasing effect of hexarelin in man.

The growth hormone (GH) response to GH-releasing hormone (GHRH) is strongly inhibited by previous administration of recombinant human GH (rhGH), likely as a consequence of a somatostatin-mediated GH negative autofeedback. Hexarelin (HEX), a synthetic hexapeptide belonging to the GH-releasing peptide (GHRP) family, possesses a GH-releasing activity greater than that of GHRH both in animals and in man. The mechanism of action of GHRPs is yet to be completely clarified, although concomitant actions at the pituitary and hypothalamic level have been hypothesized.

Short-term administration of intranasal or oral Hexarelin, a synthetic hexapeptide, does not desensitize the growth hormone responsiveness in human aging.

The function of the growth hormone-insulin-like growth factor I (GH-IGF-I) axis is reduced in aging, although the secretory capacity of somatotrope cells is preserved. Previous studies have suggested that continuous administration of GH-releasing peptides (GHRPs) results in homologous desensitization to the GH-releasing effect of the peptides. In the present study we have studied whether healthy elderly subjects would remain responsive to short-term, intermittent treatment with Hexarelin (HEX), a GHRP, and whether this treatment would result in an increase in serum IGF-I.

Growth hormone-releasing effect of oral growth hormone-releasing peptide 6 (GHRP-6) administration in children with short stature.

Growth hormone-releasing peptide 6 (GHRP-6) is a synthetic hexapeptide with a potent GH-releasing activity after intravenous, subcutaneous, intranasal and oral administration in man. Previous data showed its activity also in some patients with GH deficiency. The aim of our study was to verify the GH-releasing activity of oral GHRP-6 administration on GH secretion in children with normal short stature.

Growth hormone-releasing activity of growth hormone-releasing peptide-6 is maintained after short-term oral pretreatment with the hexapeptide in normal aging.

The reduced activity of the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis in aging may contribute to changes in body composition. As this GH insufficiency is due to hypothalamic pathogenesis, the availability of GH-releasing peptides (GHRPs), such as GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) which is active even after oral administration, might be useful to restore it. The aim of our study was to verify the effectiveness of oral administration of GHRP-6 in normal elderly subjects and to investigate whether its GH-releasing activity is maintained or vanishes after short-term oral treatment.

Arginine enhances the growth hormone-releasing activity of a synthetic hexapeptide (GHRP-6) in elderly but not in young subjects after oral administration.

In man the GH-releasing hexapeptide His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) has been shown to be active even after oral administration. On the other hand, it has been shown that arginine (ARG) totally restores the reduced somatotropic responsiveness to GHRH observed in aging. Based on the foregoing, in this study we verified the GH-releasing activity of oral GHRP-6 (300 micrograms/kg) in normal aging and the possible enhancing effect of 8 g oral ARG on the GH-releasing effect of GHRP-6.

Somatotropic function in short stature: evaluation by integrated auxological and hormonal indices in 214 children. The Italian Collaborative Group of Neuroendocrinology.

GH secretion was evaluated in 214 children and adolescents (age, 5-16 yr; 160 males and 54 females) with short stature (height, < or = 5th percentile) by assessing mean spontaneous overnight GH concentration (normal values, > or = 3 and 3.9 micrograms/L for prepubertal and pubertal subjects, respectively) and responsiveness to stimulation with GH-releasing hormone combined with pyridostigmine (normal peak values, > or = 20 micrograms/L). Plasma insulin-like growth factor-I (IGF-I) was also measured.

Repetitive GHRH administration fails to increase the response to GHRH in obese subjects. Evidence for a somatotrope defect in obesity?

Spontaneous GH secretion as well as GH response to several stimuli including GHRH have been shown to be reduced in obesity. To clarify the pathogenesis underlying these alterations, in six obese patients (3 males and 3 females, age 20-44 yrs, BMI = 42.1 +/- 2.

A neuroendocrinological approach to evidence an impairment of central cholinergic function in aging.

A hypothalamic pathogenesis for the reduced GH secretion in aging has been reported for both animal and man. To further address this issue we studied in 31 elderly normal subjects (6 males and 25 females, aged 66-90 yr) and in 22 young healthy controls (13 males and 9 females, aged 20-35 yr) the GH responses to GHRH test (GHRH29, 1 microgram/kg i.v.

Intranasal administration of neostigmine potentiates both intravenous and intranasal growth hormone (GH)-releasing hormone-induced GH release in short children.

Administration of cholinergic agonists increases both basal and GH-releasing hormone (GHRH)-induced GH secretion, probably acting via inhibition of endogenous somatostatin release. The aim of our study was to verify in two groups of children with idiopathic short stature the effect of intranasal administration of neostigmine (inNS; 3 mg), a cholinesterase inhibitor, on basal GH levels as well as on the somatotroph response to GHRH when the peptide was administered either iv (ivGHRH; 1 microgram/kg) or intranasally (inGHRH; 10 micrograms/kg). In group A (n = 6; age, 10.

The effect of galanin on baseline and GHRH-induced growth hormone secretion in obese children.

We have evaluated the effect of the administration of galanin (Gal), a newly identified hypothalamic peptide, on baseline and GHRH-induced GH rise in five obese children and in seven controls. The GH response to GHRH (hpGRF(1-29), 1 microgram/kg i.v.

Pregnancy following combined growth hormone--pulsatile GnRH treatment in a patient with hypothalamic amenorrhoea.

A patient with hypothalamic amenorrhoea and a poor response in terms of pituitary growth hormone (GH) to acute administration of growth hormone-releasing factor has been treated with pulsatile gonadotrophin-releasing hormone (GnRH) combined with GH to induce ovulation. GH was administered daily until signs of ovulation were detected. The luteal phase was supported by pulsatile GnRH only.

Effect of the potentiation of cholinergic activity on the variability in individual GH response to GH-releasing hormone.

In man the GH response to GHRH is highly variable and some normal subjects may be completely unresponsive to the neuropeptide. On the other hand, the potentiation of cholinergic activity by pyridostigmine (PD), a cholinesterase inhibitor, increases the GH response to GHRH, probably by inhibiting somatostatin release. The aim of this study was to assess the existence of intraindividual variability in the GH response to GHRH and verify the effects of PD treatment on inter- and intraindividual variability.

Long-lasting lowering of serum growth hormone and prolactin levels by single and repetitive cabergoline administration in dopamine-responsive acromegalic patients.

Cabergoline, the new long-acting dopaminergic ergoline derivative, was given orally in single doses of 0.3 and 0.6 mg to eight dopamine-responsive acromegalic patients.

Serum free thyroid hormones in different degrees of hypothyroidism and in euthyroid autoimmune thyroiditis.

Serum total and free T4 and T3, thyroxine-binding globulin (TBG) and TSH, basal and 20, 30 and 60 min after TRH (200 micrograms, iv), were evaluated in 125 hypothyroid patients (38 with severe, 23 with mild, and 64 with subclinical hypothyroidism), in 35 euthyroid subjects with autoimmune thyroiditis, and in 51 healthy controls. T4/TBG and T3/TBG ratios were also calculated. A significant decrease in all indices of thyroid function except for T3 occurred simultaneously with a significant increase in basal and TRH-stimulated TSH levels from healthy subjects to subclinical hypothyroids, from subclinical to mild and from mild to severe hypothyroids; euthyroid patients with autoimmune thyroiditis did not differ from healthy subjects.