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Biomedical subjects

Michael O Thorner

Publications and source records attributed to Michael O Thorner.

At least 19 recordsLinked to original sources
PubMed2006

Cloning of the chicken pituitary receptor for growth hormone-releasing hormone.

Details of the regulation of GH in birds are unclear. In this report, a receptor was cloned from chicken pituitary cDNA with 61% amino acid sequence identity to the human pituitary GHRH receptor. Phylogenies inferred from sequence alignments support that this is the chicken counterpart of the GHRH receptor known in mammals. Northern blotting shows that this receptor message is expressed in chicken pituitary, with lesser amounts seen in hypothalamus and brain but not in liver. The recombinant chicken receptor binds human GHRH with high affinity and specificity and signals cAMP accumulation. Surprisingly, available peptides synthesized to the published sequence for chicken GHRH-like peptide (cGHRH-LP) were inactive at this receptor. To address this we recloned the cDNA for this cGHRH-LP from chicken hypothalami. The revised sequence encodes lysine at position 21, which is consistent with all reported GHRH sequences from other species but different from the originally published chicken sequence. When this revised cGHRH-LP sequence was synthesized, it had improved but still weak potency at the cloned receptor. Consistent with the activity at the cloned receptor, human GHRH was potent when assayed in live chickens or on chicken pituitary membranes, but cGHRH-LP was not. We conclude that we have cloned a putative GHRH receptor that is homologous to mammalian GHRH receptors and functionally expressed in chicken pituitary, but that the identity of the endogenous ligand remains unclear. The chicken GHRH receptor cloned in this study can serve as a tool to identify its ligand and to clarify the evolutionary development of the regulation of GH.

Amino Acid Sequence↗
PubMed2005

The impact of short-term fasting on the dynamics of 24-hour growth hormone (GH) secretion in patients with severe radiation-induced GH deficiency.

CONTEXT: In patients with severe radiation-induced GH deficiency, we previously demonstrated that pulsatile GH secretion and diurnal rhythm are maintained in the fed state, albeit with great attenuation of the pulse amplitude. However, it remained unclear whether stressing the hypothalamic-pituitary axis could unmask neurosecretory dysregulation that is not seen under basal conditions. In addition, the impact of fasting on GH pulsatility and diurnal variation in GH-deficient patients has not been studied in detail before. STUDY SUBJECTS AND DESIGN: Twenty-four-hour GH profiles at 20-min intervals were undertaken in the fed state and in the last 24 h of a 33-h fast in eight young adult cancer survivors (two women) with severe GH deficiency after cranial irradiation for nonpituitary brain tumors in childhood and 14 matched normal controls (three women). A sensitive chemiluminescence GH assay was used with cluster analysis. RESULTS: Fasting induced a significant (P < 0.05) rise in all amplitude-dependent measures (absolute GH peak and nadir, profile mean GH, and mean pulse amplitude and area) in both groups. Pulse frequency was nonsignificantly increased (by 10%) in normals but significantly increased (by 20%) in the patients. The average increase in the individual fasting profile mean GH concentration was 3.7-fold (range 1.5-8.3) in normals, compared with 2.7-fold (range 1-4.7) in the patients (P > 0.05). Fasting amplified amplitude-related differences between patients and controls, and thus, unlike in the fed state, the day (0900-2040 h) mean GH completely demarcated patients from normals. An absolute GH peak level of 2 and 4 microg/liter and a profile mean GH level of 0.25 and 0.65 microg/liter completely separated patients from normals in the fed and the fasting states, respectively. Overall, fasting seems to induce a feminized pattern of GH secretion with relatively higher interpeak levels, preserved but diminished diurnal variation, and increased secretory disorderliness (increased approximate entropy scores). CONCLUSION: The overall pulsatile pattern of GH secretion during fasting in patients with radiation-induced GH deficiency and the relative augmentation in GH release are similar to that seen in normals emphasizing that GH neuroregulation is preserved in these patients even when the hypothalamic-pituitary axis is under physiological stress.

3-Hydroxybutyric Acid↗
PubMed2005

The dynamics of growth hormone (GH) secretion in adult cancer survivors with severe GH deficiency acquired after brain irradiation in childhood for nonpituitary brain tumors: evidence for preserved pulsatility and diurnal variation with increased secretory disorderliness.

Dynamics of GH secretion in patients with GH deficiency due to radiation damage of the hypothalamic-pituitary (h-p) axis acquired in childhood has rarely been studied. Thus, we used a sensitive chemiluminescence GH assay to analyze 24-h GH profiles (20-min sampling) from 10 adult cancer survivors with severe GH deficiency acquired after brain irradiation in childhood for nonpituitary brain tumors. An age- and sex-matched control group of 30 normal healthy volunteers, eight of whom were matched for body mass index with the patients, were also studied. Cluster analysis with gender-specific comparisons revealed a significant reduction (P < 0.05) in all amplitude-related measurements [profile mean GH levels or area under curve for GH, absolute (maximum) GH peak height, mean peak height, and mean pulse area] in patients. No differences were observed in frequency-related measurements (pulse frequency, pulse duration, and interpulse interval). Pulsatile secretion was relatively more attenuated than basal secretion in patients, and approximate entropy (ApEn) scores were significantly (P < 0.05) elevated, suggesting more disordered GH secretion. Radiation inflicts quantitative damage to the h-p axis, leading to amplitude-dependent dampening of GH secretion with relative preservation of nonpulsatile secretion. Qualitative perturbation in hypothalamic control of GH release is evident by the increase in ApEn values reflecting more disordered GH secretion. The integrity of the h-p axis and GH neuroregulation is fundamentally preserved in irradiated GH-deficient patients with a GH secretory pattern similar to that observed in normal subjects and those with GH deficiency due to other etiologies.

Adolescent↗
PubMed2005

Absence of ghrelin protects against early-onset obesity.

The gut peptide ghrelin, the endogenous ligand for the growth hormone secretagogue receptor, has been implicated not only in the regulation of pituitary growth hormone (GH) secretion but in a number of endocrine and nonendocrine functions, including appetitive behavior and carbohydrate substrate utilization. Nevertheless, recent genetic studies have failed to show any significant defects in GH levels, food intake, or body weight in adult ghrelin-deficient (Ghrl-/-) mice. Here we demonstrate that male Ghrl-/- mice are protected from the rapid weight gain induced by early exposure to a high-fat diet 3 weeks after weaning (6 weeks of age). This reduced weight gain was associated with decreased adiposity and increased energy expenditure and locomotor activity as the animals aged. Despite the absence of ghrelin, these Ghrl-/- mice showed a paradoxical preservation of the GH/IGF-1 axis, similar to that reported in lean compared with obese humans. These findings suggest an important role for endogenous ghrelin in the metabolic adaptation to nutrient availability.

Animal Feed↗
PubMed2004

Hexarelin modulates the expression of growth hormone secretagogue receptor type 1a mRNA at hypothalamic and pituitary sites.

Ghrelin and the synthetic growth hormone secretagogues (GHSs) activate a G-protein-coupled receptor (GHS-R) originally cloned from the pituitary, but which is also expressed in the hypothalamus, in other areas of the brain and in numerous peripheral tissues. Several studies have shown that growth hormone (GH)-releasing hormone (GHRH) is necessary for GHSs to exert maximal GH release in vivo. The exact mechanism of this synergism is not clear. Previous data suggest that GHSs can affect pituitary GHS-R mRNA expression; however, it is unknown whether this effect is age dependent and whether hypothalamic GHS-Rs are also affected. In this study, we tested whether (a) the synthetic GHS hexarelin regulates mRNA expression of its own receptor at the pituitary and/or hypothalamus and whether this effect is age dependent, and (b) whether short-term treatment with GHRH or, conversely, passive immunization against GHRH affects pituitary GHS-R1a mRNA expression in infant (10 days old) and young adult rats. GHS-R1a mRNA expression was measured with competitive reverse transcriptase-polymerase chain reaction. Hexarelin treatment significantly increased pituitary and hypothalamic GHS-R1a mRNA levels in normal infant rats, but not in normal young adult rats. In addition, hexarelin administration also stimulated pituitary GHS-R1a mRNA in infant as well as in young adult rats passively immunized against GHRH. GHRH treatment significantly enhanced pituitary GHS-R1a mRNA expression in GHRH-deprived young adult rats, though it did not affect the basal levels of GHS-R1a mRNA in normal infant and adult rats. These data further support the hypothesis that GHRH can affect GHS-R1a expression and that hexarelin upregulates the expression of its own receptor at the pituitary as well as the hypothalamus in an age-dependent fashion.

Age Factors↗
PubMed2004

Muscle mechano growth factor is preferentially induced by growth hormone in growth hormone-deficient lit/lit mice.

Two muscle insulin-like growth factor-I (IGF-I) mRNA splice variants (IGF-IEa and IGF-IEb) have been identified in rodents. IGF-IEb, also called mechano growth factor (MGF) has been found to be upregulated by exercise or muscle damage. Growth hormone (GH) is the principal regulator of IGF-I expression in several tissues including skeletal muscle. Therefore, we investigated the effect of chronic GH excess or disruption of GH receptor (GHR) signalling, and the acute effect of GH administration on expression of muscle IGF-I isoforms using transgenic mice that express bovine GH (bGH), GHR gene-disrupted (GHR-/-) mice and GH-deficient lit/lit mice before and after exogenous GH administration. MGF mRNA in skeletal muscle was increased in bGH mice whereas it was decreased in GHR-/- mice compared with control animals. Exogenous GH administration to dwarf lit/lit mice significantly increased muscle MGF but not IGF-IEa mRNA 4 h after treatment. Twelve hours after GH treatment, both MGF and IGF-IEa mRNAs in muscle were increased compared with vehicle-treated lit/lit mice. In contrast in GH-sufficient lit/+ mice, both MGF and IGF-IEa mRNAs were increased 4 h after and returned to the basal level 12 h after GH treatment. Hepatic IGF-I isoforms were regulated in parallel by GH. Thus, our results demonstrated that: (1) MGF mRNA in skeletal muscle is expressed in parallel with GH action; (2) MGF mRNA in muscle is produced preferentially in the situation of GH deficiency in contrast to the pattern in the GH-sufficient state; and (3) the induction of IGF-I isoforms by GH is tissue-specific.

Animals↗
PubMed2004

Regulation of full-length and truncated growth hormone (GH) receptor by GH in tissues of lit/lit or bovine GH transgenic mice.

Two truncated isoforms of growth hormone (GH) receptor (GHR) were identified in mice and in humans. The proteins encoded by these isoforms lack most of the intracellular domain of the GHR and inhibit GH action in a dominant negative fashion. We have quantified the mRNAs encoding the GHR isoforms in mouse tissues by use of real-time RT-PCR and examined the effect of GH excess or deficiency on regulation of mRNA levels of the GHR isoforms in vivo. In the liver, the truncated GHR mRNAs (mGHR-282 and mGHR-280) were 0.5 and <0.1%, respectively, the level of full-length GHR (mGHR-fl). In skeletal muscle, the values were 2-3 and 0.1-0.5% of mGHR-fl, respectively, and in subcutaneous fat, the values were 3-5 and 0.1-0.5% of mGHR-fl, respectively. The bovine GH transgenic mice showed a significant increase of mGHR-fl in liver but a significant decrease in skeletal muscle, with no difference in subcutaneous fat when compared with control mice. The lit/lit mice showed a significant decrease of mGHR-fl in liver, no difference of mGHR-fl in muscle, and a significant increase of mGHR-fl in subcutaneous fat when compared with lit/+ mice. The mRNA of mGHR-282 was regulated in parallel with mGHR-fl in all tissues of all mice examined, whereas that of mGHR-280 was not changed in either GH-excess or GH-deficient states. In conclusion, two truncated isoforms of GHR mRNAs were detected in liver, skeletal muscle, and subcutaneous fat of mice. The ratio of GHR-tr to GHR-fl mRNA was tissue specific and not affected by chronic excess or deficiency of GH.

Adipose Tissue↗
PubMed2004

Tissue-specific regulation of growth hormone (GH) receptor and insulin-like growth factor-I gene expression in the pituitary and liver of GH-deficient (lit/lit) mice and transgenic mice that overexpress bovine GH (bGH) or a bGH antagonist.

GH has diverse biological actions that are mediated by binding to a specific, high-affinity cell surface receptor (GHR). Expression of GHR is tissue specific and a requirement for cellular responsiveness to GH. IGF-I is produced in multiple tissues and regulated in part by GH through GHR. In this study, we evaluated GHR and IGF-I mRNA expression in pituitary gland and compared the levels with those derived from liver of bovine GH transgenic, GH antagonist transgenic, lit/lit mice, and their respective controls using real-time RT-PCR. In liver, both GHR and IGF-I mRNA expressions were regulated in parallel with GH action in all three animal models, and there was a strong correlation between GHR and IGF-I mRNA levels. In the pituitary gland, increased expression of IGF-I mRNA in the pituitary of bovine GH transgenic mice was observed, whereas IGF-I expression in GH antagonist transgenic or lit/lit mice was similar to that observed in control animals. There were no differences of GHR mRNA levels in pituitary gland of any groups we examined. There was also no correlation between GHR and IGF-I mRNA levels in any group in the pituitary gland. In conclusion, we found that hepatic GHR and IGF-I mRNA levels were strongly correlated with each other in chronic GH excess or deficient state, and that regulation and correlation between local GHR and IGF-I mRNA levels induced by GH is different between liver and pituitary gland.

Animals↗
PubMed2004

Lack of contribution of 11betaHSD1 and glucocorticoid action to reduced muscle mass associated with reduced growth hormone action.

11Beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) is expressed in several tissues and converts inactive glucocorticoids (GC) to active GC. 11betaHSD1 activity, evaluated by urine cortisol metabolites, is increased in patients with hypopituitarism and decreased by GH replacement. Skeletal muscle wasting is one of the major characteristics of GH deficiency (GHD). We hypothesized that increased 11betaHSD1 activity and increased GC action in skeletal muscle may play a role in the development of muscle atrophy observed in GHD patients. Glutamine synthetase (GS) mRNA in muscle has been reported to be related to GC-induced muscle atrophy. In this study, we measured mRNA levels of 11betaHSD1 and GS in skeletal muscle of GH receptor gene disrupted (GHR-/-) mice and of their age-matched wild-type mice controls to elucidate the physiological significance of 11betaHSD1 and GC in the development of GHD-associated muscle atrophy in vivo. We also measured the expression of these genes in hypertrophied muscles of giant, bovine GH transgenic mice. In skeletal muscle, although IGF-I mRNA levels were decreased in GHR-/- mice, 11betaHSD1 mRNA levels were not significantly changed compared to wild-type mice. In addition, expression level of 11betaHSD1 in muscle was lower compared to that seen in liver. GS mRNA in skeletal muscle of GHR-/- mice was not significantly different from that of controls. In bGH mice, 11betaHSD1 and GS mRNA levels were not altered compared to control mice. These data do not support a significant role of 11betaHSD1 and GC action in skeletal muscle in the development of muscle atrophy associated with GHD.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2004

Acromegaly and serum insulin-like growth factor I.

Random levels of growth hormone (GH) are usually not helpful in diagnosing either GH deficiency or GH hypersecretion because GH is secreted in a pulsatile fashion. Insulin-like growth factor I (IGF-I), however, is a good indicator of GH secretion and action, particularly at the level of the liver. There is a good correlation between IGF-I and several clinical indices of acromegaly. Measurements of both IGF-I and GH are cornerstones of biochemical diagnosis and follow-up of acromegaly, although in patients treated with pegvisomant, IGF-I levels should be followed rather than GH levels. IGF-I immunoassays differ in assay design, label, intra- and inter-assay precision, and calibrator or standard used, so IGF-I assays may be difficult to compare with one another. Hence, it is essential that the assays used in the laboratory are well validated and adequate normal ranges are available for the levels to be interpreted in a robust manner.

Acromegaly↗
PubMed2004

Growth hormone (GH) replacement therapy in adult-onset gh deficiency: effects on body composition in men and women in a double-blind, randomized, placebo-controlled trial.

Adult GH deficiency (AGHD) is characterized by an altered body composition, an atherogenic lipid profile, decreased exercise capacity, and diminished quality of life. We performed a randomized, double-blind, placebo-controlled, multicenter study in 166 subjects with AGHD to assess the effects of GH on these outcomes. GH was initiated at 0.0125 mg/kg.d, increased to 0.025 mg/kg.d as tolerated, or decreased to 0.00625 mg/kg.d for 12 months. Primary measures of efficacy included body composition, strength and endurance, and quality of life. Additional parameters included serum IGF-I concentrations, serum lipids, and bone mineral density. After 12 months, 79% of subjects remained on GH 0.0125 mg/kg.d, whereas 21% received 0.00625 mg/kg.d. GH-treated men and women demonstrated significant decreases in total body and trunk fat and increases in lean body mass over baseline. In GH-treated men, mean IGF-I SD scores exceeded age-adjusted normal ranges, whereas similar doses produced a smaller response in women. GH treatment was associated with significant improvements in total cholesterol and low-density lipoprotein (P < 0.05 for all). No significant treatment effects were observed in strength and endurance, quality of life, or bone mineral density. GH treatment was generally well tolerated. Subjects with AGHD should receive individualized GH therapy to maintain IGF-I between the mean value and +2 SD and improve body composition and cardiovascular risk factors.

Adult↗
PubMed2004

Diurnal variation in growth hormone receptor messenger ribonucleic acid in liver and skeletal muscle of lit/+ and lit/lit mice.

The present study investigated the diurnal variation in GH receptor (GHR) mRNA in liver and skeletal muscle of 3-month-old GH-deficient and -sufficient mice using quantitative real-time RT-PCR. lit/lit (GH deficient) or lit/+ (GH sufficient) mice were fed ad libitum and lights were on between 0600 and 2000. Tissues were collected at 0800-1000, 1200-1400 and 2000-2200. Hepatic GHR mRNA levels of lit/+ mice at 0800-1000 were significantly lower than those at 1200-1400 and 2000-2200. There was no significant variation in hepatic GHR mRNA of lit/lit mice. In skeletal muscle, GHR mRNA levels of both lit/+ and lit/lit mice at 1200-1400 were significantly higher than those at 0800-1000 and 2000-2200. There was also a diurnal change in hepatic IGF-I mRNA levels of lit/+ but not of lit/lit mice; the levels were lowest at 0800-1000 in lit/+ mice. On the other hand, there was no variation in IGF-I mRNA levels in skeletal muscle. These results suggest that 1) there is a diurnal variation in GHR expression in liver and skeletal muscle and the pattern of the variation is tissue specific; 2) GH deficiency blunted the diurnal variation in GHR mRNA in liver but not that in skeletal muscle; 3) IGF-I mRNA expression in liver is more closely related to GHR mRNA expression than that in skeletal muscle.

Animals↗
PubMed2004

Primary hypophysitis: a single-center experience in 16 cases.

OBJECT: The authors review their experience in the treatment of 16 patients with primary hypophysitis. METHODS: A retrospective study was undertaken to review cases of primary hypophysitis. The mean age of the patients was 47 years and there was an equal distribution of sexes. Recent pregnancy and underlying autoimmunity were noted in 50% of the patients. Two patients had undergone previous transsphenoidal operations at other centers, one for prolactinoma and another for hypophysitis. Headache, anterior pituitary deficiency, and suprasellar mass lesions were the most common presenting features. The initial presumptive diagnosis was pituitary adenoma in six patients (37.5%) and inflammatory hypophysitis in 10 (62.5%). Five patients received initial medical therapy for hypophysitis; although three (60%) responded satisfactorily, two (40%) did not and later underwent surgery. Altogether 13 patients (81.2%) underwent transsphenoidal surgery. The histological diagnoses were lymphocytic hypophysitis in 10 (76.9%) and granulomatous hypophysitis in three (23.1%) of the surgically treated patients. A coexistent Rathke cleft cyst was noted in one patient. There was no death in this series. One patient experienced postoperative cerebrospinal fluid leakage and meningitis. One patient had bilateral internal carotid artery occlusion secondary to inflammatory involvement of the cavernous sinuses and arteritis. This patient recovered and is capable of independent functional activities. CONCLUSIONS: All surgical patients experienced improvement in their headache and/or visual field defects and none had visual deterioration. None of the patients experienced any improvement in endocrine function and all required long-term hormone replacement. Transsphenoidal surgery was a safe and effective treatment especially for visual and pressure symptoms. A postoperative recurrence developed in two patients (15.4%) and the treatment modalities included steroid therapy, repeated surgery, and radiosurgery.

Adult↗
PubMed2003

Impact of abdominal visceral fat, growth hormone, fitness, and insulin on lipids and lipoproteins in older adults.

We examined the relationship between abdominal visceral fat (AVF) and plasma concentrations of lipids and lipoproteins in 19 females (F) (not on estrogen) and 31 males (M) over the age of 60 (age = 66.8 years). In addition, the effects of growth hormone (GH) release, fitness (Vo(2) peak), insulin, and glucose concentrations (both fasting and in response to an oral glucose tolerance test) on lipids were examined. Subjects were categorized by low (L) and high (H) AVF (L < 130 cm(2), H > 130 cm(2)), fat mass (FM) (above or below median value), and AVF corrected for fat mass. Factorial analysis of variance (ANOVA) showed that when subjects were divided by AVF and FM, similar results were observed with H > L (P <.05) for very-low-density lipoprotein-cholesterol (VLDL-C), triglycerides (TG), VLDL-TG, apolipoprotein (apo)-B, apo-B VLDL, cholesterol (Chol)/high-density lipoprotein (HDL), LDL/HDL, apoB/A1 and L > H for HDL, HDL(2), HDL(3), apo A1, and LDL/apo-B LDL. Gender differences were also observed with F > M for Chol, LDL, HDL, and HDL(2). When AVF was corrected for FM, these gender differences were still present. After correcting for FM, differences remained between H and L AVF groups for VLDL, TG, VLDL-TG, apo-B, apo-B LDL, apo-B VLDL, apoB/A1 (P <.05). Twenty-four hour integrated GH concentration (IGHC) was inversely related to VLDL, TG, VLDL TG, LDL TG, apoB, apoB VLDL, apoB LDL, Chol/HDL, LDL/HDL, and apoB/A1 in F, but not M (P <.05). Vo(2) peak was directly related to Chol, LDL, HDL(3), and apoB LDL with stronger relationships observed in F. Fasting insulin was related to lipids and lipoproteins in both men and women. These data suggest that, in older adults, elevated levels of AVF, FM, and AVF corrected for FM are associated with unfavorable lipid-lipoprotein profiles and extend similar findings reported in younger males and females with elevated AVF. These data also support previous findings indicating that AVF is a primary determinant of GH release.

Abdomen↗
PubMed2003

Optimizing control of acromegaly: integrating a growth hormone receptor antagonist into the treatment algorithm.

Acromegaly is associated with significant morbidities and a 2- to 3-fold increase in mortality because of the excessive metabolic action of GH and IGF-I, a marker of GH output. Reductions in morbidity correspond with decreases in IGF-I, and mortality is lowered following normalization of IGF-I or GH levels. Therefore, this has become an important end point. Current guidelines for the treatment of acromegaly have not considered recent advances in medical therapy, in particular, the place of pegvisomant, a GH receptor antagonist. Treatment goals include normalizing biochemical markers, controlling tumor mass, preserving pituitary function, and relieving signs and symptoms. Surgery reduces tumor volume and is considered first-line therapy. Radiation reduces tumor volume and GH and IGF-I levels, but the onset of action is slow and hypopituitarism typically develops. Therefore, pharmacotherapy is often used following surgery or as first-line therapy for nonresectable tumors. Dopamine agonists can be considered in patients exhibiting minimal disease or those with GH-prolactin-cosecreting tumors but will not achieve hormone normalization in most patients. Somatostatin analogs effectively suppress GH and IGF-I in most patients, but intolerance (e.g. diarrhea, cramping, gallstones) can occur. Pegvisomant, the newest therapeutic option, blocks GH action at peripheral receptors, normalizes IGF-I levels, reduces signs and symptoms, and corrects metabolic defects. Pegvisomant does not appear to affect tumor size and has few adverse effects. Pegvisomant is the most effective drug treatment for acromegaly in normalizing IGF-I and producing a clinical response; it is the preferred agent in patients resistant to or intolerant of somatostatin analogs.

Acromegaly↗
PubMed2002

IGF-I does not affect the net increase in GH release in response to arginine.

Arginine stimulates growth hormone (GH) secretion, possibly by inhibiting hypothalamic somatostatin (SS) release. Insulin-like growth factor I (IGF-I) inhibits GH secretion via effects at the pituitary and/or hypothalamus. We hypothesized that if the dominant action of IGF-I is to suppress GH release at the level of the pituitary, then the arginine-induced net increase in GH concentration would be unaffected by an IGF-I infusion. Eight healthy young adults (3 women, 5 men) were studied on day 2 of a 47-h fast for 12 h (35th-47th h) on four occasions. Saline (Sal) or 10 microg. kg(-1). h(-1) recombinant human IGF-I was infused intravenously for 5 h from 37 to 42 h of the 47-h fast. Arginine (Arg) (30 g iv) or Sal was infused over 30 min during the IGF-I or Sal infusion from 40 to 40.5 h of the fast. Subjects received the following combinations of treatments in random order: 1) Sal + Sal; 2) Sal + Arg; 3) IGF-I + Sal; 4) IGF-I + Arg. Peak GH concentration on the IGF-I + Arg day was ~45% of that on the Sal + Arg day. The effect of arginine on net GH release was calculated as [(Sal + Arg) - (Sal + Sal)] - [(IGF-I + Arg) - (IGF-I + Sal)]. There was no significant effect of IGF-I on net arginine-induced GH release over control conditions. These findings suggest that the negative feedback effect of IGF-I on GH secretion is primarily mediated at the pituitary level and/or at the hypothalamus through a mechanism different from the stimulatory effect of arginine.

Adult↗