Biomedical subjects

C Dieguez

Publications and source records attributed to C Dieguez.

At least 91 records · Page 5Linked to original sources

PubMed1998

High-affinity binding sites to the vitamin D receptor DNA binding domain in the human growth hormone promoter.

The regulation of the human growth hormone (hGH) gene by 1,25(OH)2D3 is a mechanism which is poorly understood. The objective of this study was to investigate whether the hGH gene has DNA recognition elements for the DNA binding domain of the vitamin D receptor. Using gel retardation assays and footprinting techniques, two high-affinity binding sites, denominated F1 and F2, were identified in the 5'-flanking sequence of hGH. The distal site, F1, located at -59 bp is made up of an imperfect direct repeat separated by 3 bp and showed a high degree of similarity with other known vitamin D response elements (VDREs). The proximal site, F2, located at -36 bp showed a single 7-bp sequence, which is different from other known VDREs. The location of both sites (F1 near the GHF-1/Pit-1 response element, F2 contacting the TATA box) suggests that the vitamin D receptor by itself or through interference with other transcriptional factors may modulate hGH expression.

Binding Sites↗

PubMed1998

Acute changes in free-fatty acids (FFA) do not alter serum leptin levels.

Adult↗

PubMed1998

Interaction between body composition, leptin and growth hormone status.

Administration of growth hormone (GH) induces changes in body composition, namely, increases in both bone and lean mass and a decrease in fatty tissue. However, the contrary issue, i.e. the way in which body composition affects the secretion of GH, is highly controversial. Disease states such as obesity and chronic hypercortisolism are associated with increased adiposity and/or the central distribution of fat. Ageing, characterized by excess adiposity, is also associated with impaired secretion of GH. In these states, both spontaneous and stimulated secretion of GH is severely impeded. At the other extreme, malnutrition and fasting are both associated with increased secretion of GH when confronted with most, if not all, stimuli. As the common factor in all of these situations is the increased or decreased adiposity, or the changes in energy homeostasis, it has been postulated that adipose tissue exerts a relevant role in the control of GH secretion in man. The link between adipose tissue and GH seems to be exerted through at least two signals produced by adipocytes: free fatty acids (FFA) and the recently cloned protein, leptin. An increase in FFA blocks secretion of GH, while a decrease in FFA enhances secretion. Leptin, a hormone whose main role is to regulate the intake of food and energy expenditure, seems to regulate GH secretion by acting at the hypothalamic level. In summary, body composition affects GH secretion by way of the degree of adiposity, and free fatty acids and leptin would appear to be the messages through which adipocytes participate in the regulation of GH secretion. This framework clarifies the metabolic control of GH, a hormone with profound metabolic activities.

Adipose Tissue↗

PubMed1998

Theoretical considerations in estimating the growth hormone axis in adults.

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Adipose Tissue↗

PubMed1998

Growth hormone secretion elicited by GHRH, GHRP-6 or GHRH plus GHRP-6 in patients with microprolactinoma and macroprolactinoma before and after bromocriptine therapy.

OBJECTIVE: Growth hormone-releasing peptides (GHRPs) are potent GH releasers which act at both pituitary and hypothalamic levels through specific G-protein coupled receptors, recently cloned. A synergistic effect from the simultaneous administration of GHRH + GHRP-6 on GH release is observed in normal subjects, while it is absent in patients with hypothalamo-pituitary disconnection. We studied the effects of GHRH, GHRP-6 and both secretagogues on GH release in patients harbouring pituitary tumours that may be reduced in size by medical treatment. DESIGN: Analysis of peak GH response to GHRH, GHRP-6 and GHRH plus GHRP-6 in patients with micro- and macroprolactinomas. Integrated GH response over 2 hours calculated as AUG-GH mU/l x 120 min. Analysis of delta PRL above the basal level in response to the same GH releasers. PATIENTS: Eleven patients with macroprolactinomas aged 41.2 +/- 4.8 years (range 24-75), nine patients with microprolactinomas aged 31.5 +/- 3.4 (range 22-53) and 13 healthy subjects aged 42.1 +/- 4.7 years (range 22-64) were studied. Prolactinoma patients were then treated with bromocriptine (15-20 mg orally) for 6-24 months. Tests were repeated when there was evidence of tumour shrinkage and normalized plasma prolactin concentrations. RESULTS: Peak GH response before treatment in macroprolactinoma patients was 4.9 +/- 0.9 mu/l after GHRH, 8 +/- 4 mU/l after GHRP-6 and 18 +/- 5 mU/l after GHRH + GHRP-6. Synergism was absent. AUC were 390 +/- 90; 500 +/- 100 and 1100 +/- 300 mU/l x 120 min respectively. These values were all significantly different (P < 0.05) from normal subjects and patients with microprolactinomas with peak GH 16.8 +/- 0.9 mU/l after GHRH; 43 +/- 6 mU/l after GHRP-6 and 130 +/- 10 mU/l after GHRH + GHRP-6. AUC-GH was 1200 +/- 400 after GHRH, 2200 +/- 400 after GHRP-6 and 9000 +/- 1000 mU/l x 120 min after GHRH + GHRP-6. As in normal subjects, synergism was preserved in patients with microprolactinoma (P > 0.05). After treatment with bromocriptine peak GH in patients with macroprolactinoma was 8 +/- 4 mU/l after GHRH, 22 +/- 5 mU/l after GHRP-6 and 70 +/- 20 mU/l after GHRH + GHRP-6. AUC-GH was 800 +/- 300, 1100 +/- 300 and 3500 +/- 800 mU/l x 120 min, respectively. The response of GH after GHRP-6 and GHRH + GHRP-6 improved significantly (P < 0.05) in treated patients with macroprolactinoma. There was no significant change in GH response in microprolactinoma patients after treatment with bromocriptine. Peak GH after GHRH was 30 +/- 20 mU/l, after GHRP-6 it was 75 +/- 8 mU/l and after GHRH + GHRP-6 it was 200 +/- 30 mU/l. AUC-GH was 1500 +/- 700 after GHRH, 4500 +/- 500 after GHRP-6 and 15,100 +/- 600 mU/l x 120 min. Delta prolactin after GHRP-6 did not change before and after bromocriptine treatment in patients with macroprolactinoma or microprolactinoma. CONCLUSION: GH release after GHRP-6 or GHRH + GHRP-6 is fully preserved in patients with microprolactinomas and does not differ before and after treatment with bromocriptine. Patients with macroprolactinoma have blunted responses of GH after GHRH and GHRP-6 and synergism is severely compromised. GH responsiveness to and synergistic interaction between GHRH and GHRP-6 recovers after shrinkage of macroprolactinoma with bromocriptine. Prolactin release stimulated by intravenous administration of GHRP-6 in healthy subjects was not seen in patients with micro- or macroprolactinomas.

Adult↗

PubMed1998

Enhanced growth hormone (GH) responsiveness to GH-releasing hormone after dietary restriction in patients with Cushing's syndrome.

OBJECTIVE: In patients with Cushing's syndrome, decreased growth hormone (GH) secretion is observed although the basic mechanism is not yet understood. A short-term hypocaloric diet is known to increase both spontaneous and GHRH-stimulated GH secretion in normal subjects. In order to gain further insight into the altered GH secretion in patients with Cushing's syndrome, we assessed the effect of a short-term hypocaloric diet on GH responses to GHRH in these patients. DESIGN: Two GHRH tests (1 microgram/kg i.v.) were performed, the first under basal conditions (normocaloric diet) and the second after a 3-day hypocaloric diet (650 cal/day). PATIENTS: Six female patients with untreated Cushing's disease. MEASUREMENTS: Plasma GH levels were measured by immunoradiometric assay. RESULTS: GHRH-induced GH release was impaired in patients with Cushing's disease on a normal diet (mean peak 12.4 +/- 6.4 mU/l, area under the curve (AUC) 744 +/- 332 mU/l/120 min). Following a hypocaloric diet, GH responses to GHRH were markedly enhanced in the same group of patients (mean peak 46.2 +/- 14.8 mU/l, AUC 3142 +/- 1032 mU/l/120 min, P < 0.05). CONCLUSIONS: This study demonstrates that in patients with Cushing's disease the somatotroph hyporesponsiveness to growth hormone releasing home is improved after a short-term hypocaloric diet. Therefore, blunted growth-hormone secretion in chronic hypercortisolism is a potentially reversible state and the secretory capacity of the somatotroph appears not to be severely compromised in patients with Cushing's disease.

Adolescent↗

PubMed1998

Interaction between leptin and neuropeptide Y on in vivo growth hormone secretion.

Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes that regulates food intake and energy expenditure. Leptin has recently been shown to play a stimulatory role on GH secretion. The aim of the present study was to investigate whether leptin regulation of GH secretion was mediated by hypothalamic neuropeptide Y (NPY). We assessed the effect of leptin administration (10 microg, i.c.v.) and/or NPY (4 microg, i.c. v.) on fasted rats. Furthermore we administered leptin antiserum (10 microl, i.c.v.), anti-NPY serum (5 microl, i.c.v.) or normal rabbit serum (10 microl, i.c.v.) to freely moving fed rats. Spontaneous GH secretion was assessed over 6 h with blood samples taken every 15 min. Fed rats treated with anti-NPY serum exhibited a normal ultradian GH rhythm. However, administration of anti-NPY serum (5 microl, i.c.v., at 120 min) completely reversed the suppression induced by antileptin serum (10 microl, i.c.v., at 0 min) on plasma GH levels (area under the curve, AUC, 168 +/- 72 vs. 1,287 +/- 430 ng/ml/6 h; p < 0.01). In fasted rats, following NPY administration, GH levels remained suppressed throughout the 6 h studied. Besides, NPY administration completely blunted leptin-induced GH secretion as assessed by the AUC (28.5 +/- 11 vs. 520 +/- 220 ng/ml/6 h; p < 0. 01). Thus, it is possible that NPY mediates the effects of leptin on GH secretion. Alternatively, leptin and NPY could act through parallel pathways to alter GH release with NPY overcoming the stimulatory effect exerted by leptin on plasma GH levels.

Animals↗

PubMed1998

Effect of acute pharmacological reduction of plasma free fatty acids on growth hormone (GH) releasing hormone-induced GH secretion in obese adults with and without hypopituitarism.

In obesity, there is a markedly decreased GH secretion. The diagnosis of GH deficiency (GHD) in adults is based on peak GH responses to stimulation tests. In the severely obese, peak GH levels after pharmacological stimulation are often in the range that is observed in hypopituitary patients. To distinguish obese subjects from GHD patients, it will be necessary to demonstrate that reduced GH responsiveness to a given test is reversible in the former, but not in the latter, group. Recent studies have shown that reduction of plasma free fatty acids (FFA) with acipimox in obese patients restores their somatotrope responsiveness. There are no data evaluating GH responsiveness to acipimox plus GHRH in obese adults with hypopituitarism. The aim of the present study was to evaluate the effect of acute pharmacological reduction of plasma FFA on GHRH-mediated GH secretion in obese normal subjects and obese adults with hypopituitarism. Eight obese patients with a body mass index of 34.2+/-1.2; eight obese adults with hypopituitarism, with a body mass index of 35.5+/-1.9; and six control subjects were studied. All the patients showed an impaired response to an insulin-tolerance test (0.15 U/kg, i.v.), with a peak GH secretion of less than 3 microg/L. Two tests were carried out. On one day, they were given GHRH (100 microg, i.v., 0 min), preceded by placebo; and blood samples were taken every 15 min for 60 min. On the second day, they were given GHRH (100 microg, i.v., 0 min), preceded by acipimox (250 mg, orally, at -270 min and -60 min); and blood samples were taken every 15 min for 60 min. The administration of acipimox induced a FFA reduction during the entire test. Normal control subjects had a mean peak (microg/L) of 23.8+/-4.8 after GHRH-induced GH secretion; previous acipimox administration increased GHRH-induced GH secretion, with a mean peak of 54.7+/-14.5. In obese patients, GHRH-induced GH secretion was markedly reduced, with a mean peak (microg/L) of 3.9+/-1; previous administration of acipimox markedly increased GHRH-mediated GH secretion, with a mean peak of 16.0+/-3.2 (P < 0.05). In obese adults with hypopituitarism, GHRH-induced GH secretion was markedly reduced, with a mean peak (microg/L) of 2+/-0.7; previous acipimox administration did not significantly modify GHRH-mediated GH secretion, with a mean peak of 3.3+/-1.1 (P < 0.05). The GH response of obese patients and obese adults with hypopituitarism was similar after GHRH alone. In contrast, the GH response after GHRH plus acipimox, was markedly decreased in obese adults with hypopituitarism (mean peak, 3.3+/-1.1), compared with obese patients (mean peak, 16.0+/-3.2) (P < 0.05) and control subjects (mean peak, 54.7+/-14.5) (P < 0.01). In conclusion, GH secretion, after GHRH-plus-acipimox administration, is reduced in obese adults with hypopituitarism patients, when compared with obese normal patients. Testing with GHRH plus acipimox is safe and is free from side effects and could be used for the diagnosis of GHD in adults.

Adult↗

PubMed1998

Gender differences in both spontaneous and stimulated leptin secretion by human omental adipose tissue in vitro: dexamethasone and estradiol stimulate leptin release in women, but not in men.

Leptin is a hormone secreted by the adipocytes to serve as a signal to the central nervous system to regulate energy homeostasis. Circulating leptin mainly reflects both total fat mass and the size of constituent adipocytes, although other ancillary hormonal factors may contribute to its blood concentration. Relevant gender differences in leptin concentrations have been reported, but it is not clear whether the elevated leptin levels in women are an intrinsic property of their adipocytes or merely reflect a greater amount of fat reserves. To clarify these points, a systematic study with organ culture from human omental adipose tissue either stimulated or not with steroid hormones was undertaken in samples obtained at surgery from 67 nonobese donors (33 women and 34 men). The assay was standardized in periods of 24 h ending at 96 h, with no apparent tissue damage. Each adipose tissue sample from a single donor was incubated in triplicate, and leptin results are expressed as the mean +/- SEM of the integrated secretion to the medium (area under the curve; nanograms of leptin per g tissue/48 h). Control nonstimulated samples showed a steady leptin secretion along the 96 h studied, with the peak of secretory activity reached at 48 h; afterward, the in vitro secretion reached a plateau state. Spontaneous leptin secretion in samples from 33 women (3904 +/- 347) was significantly higher (P < 0.05) than that in samples from 34 men (2940 +/- 323). Coincubation of adipose tissue with 1 mumol/L dexamethasone induced a clear-cut leptin increase (P < 0.05) in samples from women (5848 +/- 624; n = 12), but did not change the spontaneous release of leptin in samples from men (3353 +/- 741; n = 6). Similarly, coincubation of adipose tissue with 1 mumol/L estradiol induced a notable leptin increase (P < 0.05) in samples from women (5698 +/- 688; n = 9), whereas it did not alter the secretion in the male samples (3373 +/- 444; n = 6). In samples from both sexes, coincubation with 1 mumol/L estrone or progesterone had no effect, whereas 1 mumol/L forskolin significantly (P < 0.05) reduced leptin release. In conclusion, leptin secretion from omental adipose tissue in vitro 1) is significantly higher in samples from women than in samples from men, 2) is stimulated by dexamethasone and estradiol in women but not in men, 3) is not modified by progesterone or estrone in both sexes, and 4) is inhibited by forskolin in both genders. This different response to the stimulation of adipose tissue may be the biological basis for the gender differences observed in circulating levels of human leptin.

Adipose Tissue↗

PubMed1998

Preserved growth hormone (GH) secretion in aged and very old subjects after testing with the combined stimulus GH-releasing hormone plus GH-releasing hexapeptide-6.

Either spontaneous or pharmacological stimulated GH secretion is reduced with advanced age. This observation is an added difficulty for the biochemical diagnosis of GH deficiency in adults. Furthermore, the combined administration of saturating doses of GH-releasing hormone (GHRH) plus GH-releasing hexapeptide (GHRP)-6 is nowadays the most effective GH-releasing stimulus tested in a variety of settings related to altered somatotroph function. To understand whether the GH discharge elicited by the combined stimulus declines with age, 26 normal subjects of both sexes, divided into 3 age groups [adults 19-40 yr; aged 46-65 yr; and very old (75-96 yr) subjects] were studied. They were administered i.v., as bolus and in combination, 90 micrograms GHRH plus 90 micrograms GHRP-6. In the three groups, the combined administration of GHRH plus GHRP-6 elicited a GH area under the curve (microgram/L per 120 min) of 3,127 +/- 262, 3,409 +/- 573, and 4,655 +/- 737 for adults, aged, and very old subjects, respectively (nonsignificant differences). The mean GH peak was 47.5 +/- 4.5 micrograms/L for adults, 52.9 +/- 8.4 micrograms/L for aged subjects, and 76.0 +/- 11.7 for very old subjects (nonsignificant differences). Individually examined, there were no nonresponders to the combined stimulus, and all subjects (independently of age) showed a GH peak over 25 micrograms/L (the lowest peak was 27.3 micrograms/L, and the highest peak was 119.2 micrograms/L). In conclusion, the GHRH plus GHRP-6-induced GH release is well preserved in aged and very old subjects, which suggests that the GH secretory capability of the combined test is not reduced by age. This combined test may be useful for the diagnosis of GH-deficient states in adults.

Adult↗

PubMed1998

Serum leptin levels in male marathon athletes before and after the marathon run.

Leptin is a hormone produced by the adipocytes to regulate food intake and energy expenditure at the hypothalamic level. It is commonly accepted that the main determinants of leptin secretion are the net amount of body fat and the mean size of adipocytes. On the contrary, important vectors of energy flux in the organism, such as food intake and energy expended on exercise, are not thought to be regulators of that secretion. To understand whether leptin is regulated by an acute energy expenditure such as strenuous exercise, 29 male athletes who had trained for marathon running were studied before and after a marathon run and compared with 22 nonobese, age-, sex-, and body mass index (BMI)-matched sedentary controls. Controls and marathon athletes showed no differences in BMI or fat-free mass. Marathon runners showed a strong reduction in total fat mass (6.2 +/- 0.4 kg; 9.1 +/- 0.5% of body fat) compared with controls (12.3 +/- 0.5 kg; 16.1 +/- 0.5% of body fat; P < 0.05). This difference in body composition was paralleled by a mean serum leptin level that in marathonians (2.9 +/- 0.2 micrograms/L) was significantly (P < 0.05) reduced compared with that in controls (5.1 +/- 0.6 micrograms/L). It is remarkable that the ratio of leptin per kg body fat, showed a very good agreement between the two groups, 0.40 +/- 0.04 microgram/L.kg for controls and 0.46 +/- 0.03 microgram/L.kg for marathonians. In the two groups, leptin was correlated with both body weight, BMI, and fat mass (P < 0.001). The marathon trajectory was the standard 42.195 km accomplished in an average time of 3 h, 17 min, 7 s, with a calculated energy expenditure of over 2800 Cal. After the marathon run, a water imbalance occurred, with a significant decrease in body weight and an increase in serum albumin. A significant (P < 0.05) reduction in leptin values was observed after the run (2.6 +/- 0.2 micrograms/L) compared with before (2.9 +/- 0.2 micrograms/L), which was more relevant considering the relative hemoconcentration. In conclusion, 1) compared with sedentary subjects, leptin levels are reduced in male marathon runners in parallel with the relevant reduction in total body fat; 2) expressed as a ratio of leptin per kg body fat, no differences were observed between marathonians and controls; and 3) after an energy expenditure of 2800 Cal in the marathon run, a reduction in leptin levels occurred. Strong changes in energy expenditure may regulate serum leptin levels in man.

Adult↗

PubMed1998

Serum leptin and insulin concentrations in patients with insulinoma before and after surgery.

Inferential studies suggest that circulating insulin concentrations positively regulate leptin secretion by adipocytes. In humans, however, insulin requires prolonged periods of time, and relatively artificial set-ups before a relationship with leptin can be observed. In the present work, serum leptin concentrations were measured in five patients with insulinoma before and one month after surgery and in five control subjects matched by sex and body mass index (BMI). The control subjects presented a mean serum leptin concentration of 6.7+/-1.5 microg/l and a BMI of 24.9+/-1.1. The mean serum leptin concentration in patients with insulinoma was 11.8+/-3.1 microg/l (P < 0.05 vs controls), with a BMI of 26.3+/-1.9. After surgery, there was a non-significant reduction in BMI (25.8+/-1.7), and a clear reduction in serum leptin concentration (5.6+/-2.4 microg/l, P < 0.05 vs pre surgical values and no difference vs control subjects). The fasting area under the curve (AUC) of insulin concentration (in mU/l per 120 min) before surgery was 14421+/-4981 and after surgery was 1306-/+171 (P < 0.05). Before surgery, serum leptin concentrations significantly correlated with BMI (r = 0.71) and AUC of insulin (r = 0.82), a correlation that was lost after surgery. In conclusion, serum leptin concentrations are significantly elevated in patients with chronically high insulin levels due to insulinoma. After surgical treatment and normalization of insulin values, leptin levels return to normal.

Adult↗

PubMed1997

Serum immunoreactive leptin concentrations in patients with anorexia nervosa before and after partial weight recovery.

Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes. Serum leptin concentrations increase in correlation with the percentage of body fat, but besides that little is known about the physiological actions of leptin in humans. In order to understand the role of leptin in severe malnutrition, in the present work 10 patients recently diagnosed with anorexia nervosa were studied both before and 2 months later, after partial weight recovery, and were compared with 18 normal-weight women as controls. Leptin was measured by a newly developed radioimmunoassay and both IGF-I and IGFBP-3 were measured by commercial radioimmunoassays. The mean (+/-SE) serum leptin concentrations (in microgram/liter) were 18.1 +/- 2.0 in control women with BMI of 21.1 +/- 0.3, significantly higher (P < 0.01) than that in the anorexia nervosa patients at diagnosis (2.2 +/- 0.1, BMI 15.3 +/- 0.6). These differences were also observed in IGF-I values (microgram/liter) that were 228.0 +/- 14.6 in controls and 157.4 +/- 28.7 in anorexia nervosa patients (P < 0.02). No differences were observed in IGF-BP3. After treatment, patients with anorexia nervosa experienced an increase in BMI (17.1 +/- 0.5, P < 0.0001 vs before) although they were still underweight. The partial recovery in weight led to a complete normalization of IGF-I levels (214.0 +/- 21.0 micrograms/liter) and to an enhancement in leptin levels (3.3 +/- 0.5 micrograms/liter; P < 0.03 vs before treatment), though still lower than those in normal-weight women (P < 0.05). Individually analyzed, a large dispersion was observed in control subjects, with leptin levels ranging from 5.5 to 38.7 micrograms/liter, while in all anorexia nervosa patients leptin levels were under 3 micrograms/liter. A treatment-induced increase in body weight led to an increase in leptin levels in 7 out of the 10 anorexia nervosa patients studied and the 3 patients with no increase in leptin were all initially under the 14.5 BMI. In conclusion, leptin levels are severely reduced in anorexia nervosa patients with severe malnutrition, and a significant rise occurred after partial weight recovery. There seems to be a level of BMI below which leptin levels do not drop further but also do not increase despite weight gain. While IGF-I reflects the energy intake of the previous few weeks, the serum leptin concentration reflects the true status of the adipose stores, a fact that has useful clinical implications.

Adult↗

PubMed1997

Influence of endogenous cholinergic tone and growth hormone-releasing peptide-6 on exercise induced growth hormone release.

OBJECTIVE: The neuroendocrine mechanisms of exercise-induced GH release remain incompletely understood. In this study we have investigated the influence of endogenous cholinergic tone and growth hormone-releasing peptide-6 (GHRP-6) on exercise induced GH release. DESIGN: Analysis of responses of serum GH to administration of pyridostigmine (PD, 120 mg, orally) or GHRP-6 (100 micrograms, i.v.), to exercise alone, and to the combinations of PD plus exercise or GHRP-6 plus exercise. An indirect estimation of the secretory pattern of GH was calculated by the deconvolution technique. Exercise was performed on a bicycle ergometer with a 20-minute workload near the individual lactate threshold of 4 mmol/l. The five tests were performed in random order after an overnight fast, and at least 3 days apart. SUBJECTS: Eleven healthy, non-obese male subjects (age 23.9 +/- 0.3 years, body mass index 23 +/- 0.7 kg/m2, VO2 max: 52.4 +/- 2.0 ml/min/kg body weight; mean +/- SEM) participated in this study. MEASUREMENTS: Serial blood samples from an indwelling catheter were taken before, during and after exercise for analysis of GH (IRMA), lactate (YSI 2300) and haematocrit (micromethod). RESULTS: Irrespective of the tests, peak values of GH were found between the 18th and 26th minute. The secretory pattern showed differences between the tests. Exercise alone induced relatively short lasting peaks of medium amplitude, whereas PD induced long lasting peaks with low amplitudes. PD plus exercise showed additive effects on the amplitude of GH peaks. GHRP-6 induced long lasting peaks with high amplitude, and GHRP-6 plus exercise also had additive effects on the amplitude. CONCLUSIONS: The increase in frequency and amplitude of GH peaks, which occurred during the GHRP-6 plus exercise, indicates that exercise-induced GH release is not mediated through an increment in the release of an endogenous GHRP-6-like ligand, favouring the possibility that exercise-induced GH release is mediated through an increase in endogenous GHRH release.

Adult↗

PubMed1997

Serum leptin concentrations in patients with anorexia nervosa, bulimia nervosa and non-specific eating disorders correlate with the body mass index but are independent of the respective disease.

OBJECTIVE: Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes. Serum leptin concentrations increase in correlation with the percentage of body fat, but little else is known about the physiological actions of leptin in humans. The aim of this study was to determine the role of leptin in severe eating disorders, and whether its levels are correlated with the specific disease or exclusively with body weight. TESTS: Serum concentrations of human leptin were analysed by specific radioimmunoassay and compared with the individual body mass indexes (BMI). The correlations between serum leptin concentrations and BMI, age and height were analysed. PATIENTS: A total of 65 women were studied: 25 patients with anorexia nervosa, 20 women with bulimia nervosa, 6 women with a diagnosis of nonspecific eating disorder, and 14 normal-weight women who acted as controls. At the time of the study, the patients were non-cured, under treatment, and at different stages of therapeutic evolution. MEASUREMENTS: Plasma leptin levels were measured by specific radioimmunoassay. RESULTS: The mean serum leptin in the normal-weight women was 10.5 +/- 1.1 micrograms/l, compared with 7.6 +/- 1.1 micrograms/l in the anorexia nervosa patients (P < 0.05). This reduction in leptin levels was paralleled by the differences in BMI (21.4 +/- 0.4 vs 18.8 +/- 0.2) P < 0.05. These differences between the controls and anorexia nervosa patients were not observed in patients with bulimia nervosa who had a mean serum leptin level of 9.9 +/- 1.4 micrograms/l and BMI of 21.3 +/- 0.6, neither significantly different from controls. On the contrary, patients with non-specific eating disorders showed a large reduction in BMI (17.9 +/- 1.2, P < 0.05 vs control), and a parallel reduction in serum leptin levels, 4.5 +/- 1.0 (P < 0.05 vs controls). When individual values of leptin were plotted against BMI a wide range was observed in all groups; in the control subjects from 5.6 to 17.7 micrograms/l, in anorexia nervosa patients from 2.1 to 28.1 micrograms/l, in patients with bulimia nervosa between 2.6 and 25.9 micrograms/l, and in women with non-specific eating disorder from 2.0 to 8.9. No correlation was observed with the specific disease but in each group a significant correlation was observed only with BMI. CONCLUSIONS: Serum leptin levels in three groups of patients affected by severe eating disorders are not related to the specific pathology but are correlated with the individual BMI. The analysis of leptin values may be a useful index of assessing the adipose tissue stores in the clinical setting, but will be of no help for diagnosis nor prognosis of severe eating disorders.

Adult↗

PubMed1997

Absence of desensitization by hexarelin to subsequent GH releasing hormone-mediated GH secretion in patients with anorexia nervosa.

OBJECTIVE: Both the basal levels and the neuroregulation of GH secretion are perturbed in patients with anorexia nervosa. It is unknown if these alterations are due to severe undernutrition or if they reflect basic neurotransmitter alterations of the patient's neural pathways. On the other hand, prior administration of the GH secretagogue hexarelin in normal subjects blocks the GH-releasing capability of GH releasing hormone (GHRH) administered 2 hours later. In the present work a sequential test was performed using the administration of hexarelin as first stimulus followed 120 minutes later by GHRH. The two aims of the study were: (a) to evaluate the interaction of GHRH and hexarelin, and (b) to further understand the alterations in GH neuroregulation in patients with anorexia nervosa. DESIGN: The GH stimuli used were hexarelin (1 micrograms/kg i.v.), a GH stimulus whose main action is hypothalamic, followed 120 minutes later by GHRH (1 micrograms/kg i.v.) as a pituitary stimulus. Each woman was tested once. PATIENTS: Thirty-two woman matched for age participated in the study: six normal-weight women as controls, 14 women with anorexia nervosa, seven women with secondary amenorrhoea due to voluntary weight loss for aesthetic reasons, and five normal-weight women after 72 hours of a controlled hypocaloric diet (800 cal/day). MEASUREMENTS: Plasma GH levels were measured by time-resolved fluoroimmunosasay, each value shown is the mean +/- SE in mU/l. RESULTS: The administration of hexarelin to the normal-weight women induced a clear-cut GH secretion (expressed as mean +/- SE of GH peak in mU/l of 77.5 +/- 21.8, but blocked the GH-releasing capability of GHRH administered 120 minutes later (6.6 +/- 2.8, P < 0.05). In contrast, the women with anorexia nervosa showed a normal GH response after the two stimuli: hexarelin 64.8 +/- 9.2. GHRH 71.1 +/- 14.2. The absence of heterologous desensitization was specific to anorexia nervosa, because the women with amenorrhoea due to voluntary weight loss but with a normal energy intake showed a pattern similar to the controls (GH after hexarelin 60.3 +/- 9.5 and to GHRH 120 minutes later 6.2 +/- 1.0 (P < 0.05)). Similarly, the women after the short-term hypocaloric diet showed a hexarelin-mediated GH secretion of 99.6 +/- 17.8, which blunted the subsequent administration of GHRH (GH mean peak of 9.9 +/- 2.9, P < 0.05 vs hexarelin). CONCLUSIONS: In the normal subjects, the administration of hexarelin induced clear-cut GH secretion, but inhibited the action of GHRH when administered 120 min later, while this heterologous desensitization was not observed in the patients with anorexia nervosa. This sequentially delayed test may be of some value in the clinical setting for assessing the status of patients with anorexia nervosa.

Adult↗

PubMed1997

Neuropharmacological assessment of growth hormone secretion.

The biochemical diagnosis of individuals who are either deficient in growth hormone (GH) or who have alterations in the normal pattern of GH secretion is difficult. The uncertainty surrounding diagnosis reflects the lack of a thorough understanding of the physiology of GH secretion and of the hypothalamic hormones involved. At least three hormones are implicated: GH-releasing hormone (GHRH), somatostatin and the endogenous ligand of the GH secretagogue receptor, although the role that each plays in the release of GH is not clear from the available experimental evidence. In such a situation, most of the dynamic tests of GH secretory capacity in humans need to undergo a 'trial and error' process before being validated. The search for the 'gold standard' test of GH secretion is ongoing, and the combination of GHRH plus GH secretagogues will probably play an important role in future clinical diagnosis.

Growth Hormone↗

PubMed1997

Growth hormone secretagogues in pathological states: diagnostic implications.

The identification and cloning of the receptor for synthetic growth hormone (GH) secretagogues, even before the endogenous ligand has been identified or its precise physiological role established, suggests that there is a novel target of action for this class of drug. In an attempt to select patients who will benefit from GH treatment, GH secretagogues are being evaluated for their usefulness in diagnosing GH deficiency. The effects of GH-releasing peptides (GHRPs) on GH release as a function of age and metabolic status, and in different neuroendocrine pathologies, are described, as are the different mechanisms of action, potency and reproducibility of the response to GHRPs compared with GH-releasing hormone (GHRH). GHRPs offer the advantage over GHRH in natural models of deranged GH secretion in that, in various metabolic states (e.g. obesity, anorexia nervosa and non-insulin-dependent diabetes mellitus), the GH response to GHRH is more impaired than it is to GHRPs. However, in some neuroendocrine pathologies, the reverse is true. Thus, both secretagogues provide separate information on the physiological status of somatotrophs.

Anorexia Nervosa↗