scholarly journals The effects of human leptin fragment(126-140) on pituitary functions in man

2003 ◽  
pp. 407-412 ◽  
Author(s):  
K Hanew

OBJECTIVE: The effects of human leptin fragment(126-140) on pituitary function in eight healthy, non-obese men were studied. METHODS AND DESIGN: The effects of the fragment on spontaneous secretion of pituitary hormones and endogenous leptin, as well as on GHRH-induced GH secretion were examined. RESULTS: After the administration of the fragment (50 microg i.v. for 150 min), the mean nadir value and 45 min value were significantly lower than that of the control study. Endogenous leptin levels did not decrease significantly following the administration of the leptin fragment. Other pituitary hormones were not affected by the fragment. The area under the curve of the GH response to GHRH(1-44)NH(2) (10 microg, i.v. from 0 to 75 min) was also significantly inhibited by the combined administration of the leptin fragment (100 microg i.v. from -30 to 75 min) (P<0.001). Three subjects were re-examined with larger doses of the leptin fragment (200-400 microg), and even greater GH suppression was observed. CONCLUSIONS: These results indicate that human leptin fragment(126-140) has an inhibitory role in GH secretion, since when administered exogenously this fragment significantly suppressed spontaneous and, in a dose-response manner, GHRH-induced GH secretion. Clear effects of the fragment on other pituitary hormones and an inhibitory effect on endogenous leptin secretion were not observed in this study.

1995 ◽  
Vol 133 (3) ◽  
pp. 300-304 ◽  
Author(s):  
Emanuela Arvat ◽  
Laura Gianotti ◽  
Josefina Ramunni ◽  
Silvia Grottoli ◽  
Pier Carlo Brossa ◽  
...  

Arvat E, Gianotti L, Ramunni J, Grottoli S, Brossa PC, Bertagna A, Camanni F, Ghigo E, Effect of galanin on basal and stimulated secretion of prolactin, gonadotropins, thyrotropin, adrenocorticotropin and cortisol in humans. Eur J Endocrinol 1995;133:300–4. ISSN 0804–4643. Galanin enhances both baseline and growth hormone-releasing hormone (GHRH)-induced GH secretion both in animals and in man. Although galanin has a clear influence on the secretion of other anterior pituitary hormones in animals, in man it increases prolactin (PRL) slightly but does not affect spontaneous thyrotropin (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH) or adrenocorticotropin (ACTH) secretion. The aim of our study was to verify the effect of galanin on basal and releasing hormone-stimulated release of gonadotropins, PRL, TSH, ACTH and cortisol secretion. As GH release has been shown to be inhibited by corticotropin-releasing hormone (CRH), we also studied the effect of CRH on galanin-stimulated GH increase. The effect of porcine galanin (15 μg/kg iv infused in 60 min) alone and in combination with thyrotropin-releasing hormone (TRH, 200 μg iv bolus), CRH (100 μg iv bolus) and gonadotropin-releasing hormone (GnRH, 100 μg iv bolus) on GH, PRL, TSH, ACTH, cortisol, FSH and LH secretion in seven normal young women (aged 25–30 years) was studied. Galanin infusion caused an increase in serum GH levels (p < 0.02) but failed to modify significantly the spontaneous PRL, LH, FSH, TSH, ACTH and cortisol secretion. The combined administration of TRH, GnRH and CRH caused a significant increase in PRL (p < 0.02), LH (p < 0.02), FSH (p < 0.02), TSH (p < 0.02), ACTH (p < 0.02) and cortisol (p < 0.05), but not in GH levels. Galanin infusion significantly enhanced the PRL response to TRH + GnRH + CRH administration (p < 0.05), while the releasing hormone-stimulated levels of LH, FSH, TSH, ACTH and cortisol were not influenced by galanin. The GH release after the combined administration of GAL, TRH, GnRH and CRH was similar to that observed after galanin alone. In conclusion, the present results support the view that galanin plays a role in the control of GH and PRL secretion in humans. On the other hand, galanin does not seem to have any influence on the secretion of the other pituitary hormones in humans. However, a role for galanin in the modulation of hypophysiotropic neurohormone function at the hypothalamic level cannot be ruled out. Ezio Ghigo, Divisione di Endocrinologia, Ospedale Molinette. Corso Dogliotti 14, 10126 Torino, Italy


1989 ◽  
Vol 121 (5) ◽  
pp. 714-720 ◽  
Author(s):  
Peter A. van Liessum ◽  
Gerlach F. Pieters ◽  
Anthony G. Smals ◽  
Ad R. Hermus ◽  
TheoJ. Benraad ◽  
...  

Abstract. The recommended dosage schedules for intermittent sc therapy with the somatostatin analogue octreotide in acromegaly vary widely, from 100 to 1500 μg daily. As acute administration of octreotide has been shown to predict its long-term response, we performed a single-dose response study in 5 patients with active acromegaly using doses of 25, 50, 100, 200 and 400 μg octreotide as well as a placebo injection. Plasma GH of 2 patients did not normalize after any of the injections, but nadir plasma GH overall gradually decreased as doses were increased from 25 to 400 μg. The 400 μg octreotide dose was superior with regard to the duration of plasma GH suppression to below 5 μg/l or 25% of the basal GH level, the mean GH as a percentage of the basal level over the first 4 and 8 h, and the integrated reduction of plasma GH during the first 4 and 8 h. The postprandial integrated insulin secretion during the first 3 h after injection of the octapeptide was significantly lower after 50, 100 and 400 μg than after the placebo injection. The mean plasma glucose as a percentage of the basal level during the first 8 h was significantly higher after octreotide after the 200 and 400 μg injections. Minor adverse events were seen in 2 patients after injection of 200 and 400 μg octreotide. Within the limitations of this single-dose response study it was concluded that injection of 400 μg octreotide yields the best results with regard to suppression of GH secretion, whereas the 50, 100 and 200 μg doses are superior to 25 μg, but do not differ from each other.


2001 ◽  
Vol 168 (1) ◽  
pp. 59-66 ◽  
Author(s):  
WM Lee ◽  
M Diaz-Espineira ◽  
JA Mol ◽  
A Rijnberk ◽  
HS Kooistra

The pulsatile secretion patterns of GH were investigated in seven beagle bitches by collecting blood samples every 10 min for 6 h during euthyroidism and 1.5 years after induction of primary hypothyroidism. Hypothyroidism was induced by surgical removal of the thyroid gland and subsequent destruction of any remnant thyroid tissue by oral administration of sodium [(131)I]iodide. Some of the physical changes observed in the dogs with primary hypothyroidism mimicked those of acromegaly. During both euthyroidism and hypothyroidism GH was secreted in a pulsatile fashion. The mean (+/-s.e.m. ) basal plasma GH concentration was significantly higher (P=0.003) in the hypothyroid state (4.1+/-1.6 microg/l) than in the euthyroid state (1.2+/-0.4 microg/l). Likewise, the mean area under the curve (AUC) for GH above the zero-level during hypothyroidism (27.0+/-10.0 microg/lx6 h) was significantly higher (P=0.004) than that during euthyroidism (11.7+/-2.0 microg/l x 6 h). The mean AUC for GH above the baseline was significantly lower (P=0.008) during hypothyroidism (2.4+/-0.8 microg/l x 6 h) than during euthyroidism (4.5+/-1.8 microg/lx6 h), whereas there was no significant difference in GH pulse frequency. The mean plasma IGF-I level was significantly higher (P<0.01) in the hypothyroid state (169+/-45 microg/l) than in the euthyroid (97+/-15 microg/l). The results of this study demonstrate that primary hypothyroidism in dogs is associated with elevated basal GH secretion and less GH secreted in pulses. This elevated GH secretion has endocrine significance as illustrated by elevated plasma IGF-I levels and some physical changes mimicking acromegaly. It is discussed that the increased GH release in hypothyroid dogs may be the result of the absence of a response element for thyroid hormone within the canine pituitary GH gene and alterations in supra-pituitary regulation.


1993 ◽  
Vol 138 (2) ◽  
pp. 211-218 ◽  
Author(s):  
J. Muruais ◽  
A. Peñalva ◽  
C. Dieguez ◽  
F. F. Casanueva

ABSTRACT His-d-Trp-Ala-Trp-d-Phe-Lys-NH2 (GHRP-6) is a synthetic peptide unrelated to any known hypothalamic-releasing hormone including growth hormone-releasing hormone (GHRH). Interestingly, this peptide induces a dose-related increase in plasma GH levels in all species tested so far. The aim of this study was to investigate the action of GHRP-6 alone or in combination with GHRH on GH release in dogs. In addition, the activation or blockade of endogenous cholinergic tone and α-1 adrenoceptors on GHRP-6-stimulated GH secretion was assessed. In adult Beagle dogs (n = 10), GHRP-6 (90 μg i.v.) increased basal GH levels from 2·6 ± 1·5 to 14·4 ± 3·1 μg/l (mean ± s.e.m.) after 15 min. GHRH (50 μg i.v.) induced a GH peak of 9·7 ± 2·2 μg/l at 15 min. The combined administration of GHRP-6 and GHRH strikingly potentiated canine GH release with a peak of 54 ± 9·0 μg/l (P <0·01). Pretreatment with the cholinergic agonist pyridostigmine (30 mg per os) increased GHRP-6-stimulated GH secretion (37·9 ± 10·1 μg/l P <0·05), while the muscarinic blocker atropine (100 μg i.v.) completely abolished (GH peak lower than 2 μg/l) the stimulatory action of GHRP-6. On the other hand, administration of the α-2 adrenergic agonist clonidine (4 pg/kg i.v.) increased basal plasma GH levels without affecting GH responses to GHRP-6. Finally, while the α-1 adrenergic agonist methoxamine (5 mg i.v.) did not significantly increase GH responses to GHRP-6, administration of the α-1 adrenoceptor antagonist prazosin (20 mg i.v.) reduced GHRP-6-induced GH secretion (area under curve, 206 ± 39 vs 557 ± 172, P <0·05). In summary, the synergistic effect of the combined administration of maximal doses of GHRP-6 and GHRH suggests that these two peptides act through different mechanisms. The finding that cholinergic drugs were able to modulate the GH secretion elicited by GHRP-6 argues against the hypothesis that such a peptide acts by influencing hypothalamic somatostatin release and suggests that it acts directly at the pituitary level. Finally, the unexpected lack of effect of clonidine and the inhibitory effect of prazosin on GHRP-6-induced GH secretion suggests that the role of α-adrenergic pathways in GH secretion is more complex than previously thought. Journal of Endocrinology (1993) 138, 211–218


Author(s):  
J. Santoantonio ◽  
L. Yazigi ◽  
E. I. Sato

The purpose of this study was to investigate the personality characteristics in adolescents with SLE. The research design is a case-control study by means of the Rorschach Method and the Wechsler Intelligence Scale. Study group: 30 female adolescents with lupus, 12–17 years of age. The SLE Disease Activity Index was administered during the period of psychological evaluation. Control group: 32 nonpatient adolescents were matched for age, sex, and socioeconomic level. In the Wechsler Intelligence Scale the mean IQ of the experimental group was significantly lower than that of the control group (77 and 98, respectively, p < .001). In the Rorschach, the lupus patients showed greater difficulty in interpersonal interactions, although they displayed the resources to process affect and to cope with stressful situations. A positive moderate correlation (p = .069) between the activity index of the disease and the affect constriction proportion of the Rorschach was observed: the higher the SLEDAI score, the lower the capacity to process affect. There is a negative correlation between the activity index of the disease and the IQ (p = .001): with a higher activity index of the disease, less intellectual resources are available.


1967 ◽  
Vol 56 (4) ◽  
pp. 619-625 ◽  
Author(s):  
Hans Jacob Koed ◽  
Christian Hamburger

ABSTRACT Comparison of the dose-response curves for LH of ovine origin (NIH-LH-S8) and of human origin (IRP-HMG-2) using the OAAD test showed a small, though statistically significant difference, the dose-response curve for LH of human origin being a little flatter. Two standard curves for ovine LH obtained with 14 months' interval, were parallel but at different levels of ovarian ascorbic acid. When the mean ascorbic acid depletions were calculated as percentages of the control levels, the two curves for NIH-LH-S8 were identical. The use of standards of human origin in the OAAD test for LH activity of human preparations is recommended.


1974 ◽  
Vol 75 (3) ◽  
pp. 497-502
Author(s):  
Mayer B. Davidson ◽  
Roger M. Steele

ABSTRACT Since fructose is normally metabolized in diabetics and has recently been shown to stimulate GH secretion, it was used to assess GH responses in diabetics. Fourteen diabetics (9 on insulin) and 8 controls matched for weight were studied. Fructose, infused over 10 min, was compared to arginine, infused over 30 min, both at 0.5 g/kg. Samples were collected at 0, 30, 60, 90 and 120 min and GH responses assessed as area under the curve minus the fasting area. There was no significant difference between the GH responses in diabetics and controls to either agent. Responses to arginine and fructose were significantly correlated (r = 0.60, P < 0.01) in all subjects, but not related to therapy, duration of disease or fasting glucose (75–287 mg/100 ml) in the diabetics. Oral glucose blunted the GH response to fructose in 2 controls. It is concluded that 1) fructose can stimulate GH secretion in male diabetics; 2) however, fructose-stimulated GH responses are not increased in diabetes mellitus.


Author(s):  
V. B. Dolgo-Saburov ◽  
N. I. Chalisova ◽  
L. V. Lyanginen ◽  
E. S. Zalomaeva

In an organotypic culture, an investigation was conducted into combined effects of cyclophosphamide DNA as synthesis inhibitor used to model a resorptive action of mustard gas, and cortexin polypeptide or each of 20 encoded amino acids on the development of cell proliferation in cerebral cortex explants of the rat. The combined administration of cyclophosphamide together with cortexin or with each of the 20 encoded amino acids, except glycine, showed suppression of the cytostatic agent inhibitory effect. Thus, cortexin and amino acids have a protective effect on cell proliferation in the tissue culture of the central nervous system under the action of mustardlike substances.


2018 ◽  
Vol 15 (1) ◽  
pp. 74-78
Author(s):  
Mohammadali Nazarinia ◽  
Asghar Zare ◽  
Mohammad javad Fallahi ◽  
Mesbah Shams

Background:Systemic sclerosis is a disorder of connective tissue with unknown cause, affecting the skin and internal organs, characterized by fibrotic changes.Objective:To determine the correlation between serum homocysteine level and interstitial lung involvement in systemic sclerosis. </P><P> Materials and Methods: In this case – control study, 59 patients who fulfilled the ACR/EULAR classification criteria for systemic sclerosis and were referred to Hafez Hospital of Shiraz, Iran, were included as the case group. Fifty nine healthy subjects were involved as the control group. Patients were divided into two groups based on interstitial lung involvement and two subtypes, diffuse and limited type. Serum homocysteine, vitamin B12, and folate levels compared between the controls, and cases groups.Results:Of 59 case and control group, 53 (%89.8) were female and the mean age did not differ in both groups (P=0.929). Thirty five (%59.3) patients had interstitial lung involvement and 38(%64.4) had diffuse cutaneous systemic sclerosis. The mean serum homocysteine level was 13.9±6.3 µmol/L in the case and 13.7±9.2 µmol/L in the control group (P=0.86). The mean serum homocysteine level did not differ between the patients with and without interstitial lung involvement (P=0.52). The patients with lung involvement was older than those without lung involvement (P=0.004). Lung disease was more common in diffuse type (P=0.014).Conclusion:In our study, serum homocysteine level did not differ between the patients and healthy subjects. Also, there was no correlation between serum homocysteine level and lung involvement, but lung involvement was more common in older patients and also diffuse subtype.


2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
B. Herman ◽  
F. Mandel

Objective:There appears to be no dose-response effect for pregabalin at doses of 300-600 mg, and a modest dose-response effect in the range of 150-300 mg. The goal of the current investigation was to determine the effect of the starting dose on the speed of onset of anxiolytic efficacy.Methods:Data were analyzed from 7 trials of outpatients with DSM-IV GAD and a HAM-A total score ≥18. Starting doses of pregabalin ranged from 100 mg (N=301) or 150 mg (N=104), to 200 mg (N=167) and 300 mg (N=388). Assessment of early improvement included the HAM-A total score and CGI-Severity and Improvement scores.Results:The mean Week 1 HAM-A change score was similar for a starting dose of 200 mg/d with no titration (-8.24) when compared to patients who started on 200 mg/d and then titrated up to 400 mg/d on Day 4 (-8.64). The mean Week 1 HAM-A change score was somewhat higher for patients started on 300 mg/d, and then titrated to 450 mg/d on Day 4/5 (-8.84) when compared to patients started on a lower (100/150 mg/d) dose and titrated on Day 5 to 400/450 mg/d (-7.32). Starting on a dose of 300 mg/d with no titration resulted in an intermediate Week 1 change score (-7.87). The interaction of starting dose and titration schedule with baseline anxiety severity will be summarized in detail.Conclusion:The initial dose of pregabalin appears to have only a weak effect on the speed of onset of anxiolytic improvement.


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