Growth hormone and somatostatin gene expression in pituitary adenomas with active acromegaly and minimal plasma growth hormone elevation

1990 ◽  
Vol 122 (6) ◽  
pp. 745-752 ◽  
Author(s):  
Patrick Pagesy ◽  
Jacques Y. Li ◽  
Françoise Rentier-Delrue ◽  
Olivier Delalande ◽  
Yves Le Bouc ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Northern Blot Analysis ◽  
Secretory Activity ◽  
Ultrastructural Level ◽  
Wide Range ◽  
Igf I ◽  
Gh Gene ◽  
Basal Plasma ◽  
Active Acromegaly ◽  
Plasma Gh

Abstract. Some patients with active acromegaly have elevated plasma IGF-I concentrations with only minimal elevation of plasma GH. We compared adenomatous GH and SRIH expression in 3 such patients (patients No. 1, 2 and 3; basal plasma GH level < 4 μg/l) and in 3 acromegalic patients with high basal plasma GH level (patients No. 4, 5 and 6; 51.7 ± 16.1 μg/l, mean ± sem). By immunocytochemistry, all the tumours proved to be somatotropic adenomas. At the ultrastructural level, signs of low secretory activity were observed in adenomas from patients No. 2 and 3. Perifused adenoma cells of patients No. 1, 2 and 3 released very little GH compared with those of patients No. 4, 5 and 6 (1± 0.37 vs 51.5± 34.1 μg · (10−6 cells) · min−1, p< 0.001). Adenoma SRIH content was 65.7 and 30.6 pg/mg proteins in patients No. 1 and 2, whereas it was undetectable in the others (patients No. 4, 5 and 6). Northern blot analysis showed that the GH gene was poorly expressed in the adenomas from patients No. 1, 2 and 3 compared with the adenomas from patients No. 4, 5 and 6. SRIH mRNA was detected in all 6 adenomas. However, the signal was more intense in the adenomas from patients No. 1, 2 and 3 than in those from patients No. 4, 5 and 6. In conclusion, because of the variability of the biosynthetic and secretory potential of the somatotropic adenomas, patients harbouring this type of pituitary tumours can exhibit a wide range of plasma GH levels. In acromegaly with minimal elevation of plasma GH, the synthesis of SRIH by the adenoma cells themselves could play a role in the inhibition of GH expression.

Impaired secretion of growth hormone-releasing hormone, growth hormone and IGF-I in elderly men

1991 ◽  
Vol 124 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Hiroshi Bando ◽  
Chenyu Zhang ◽  
Yukinobu Takada ◽  
Ryuichi Yamasaki ◽  
Shiro Saito
Keyword(s):  
Growth Hormone ◽  
Young Men ◽  
The Elderly ◽  
Elderly Group ◽  
Elderly Men ◽  
Age Related ◽  
Igf I ◽  
Basal Plasma ◽  
Plasma Gh ◽  
Ghrh Test

Abstract. The GHRH test and L-dopa test were performed in 12 normal young men (24.1 ± 1.1 years) and 12 normal elderly men (77.8±1.4 years) to investigate age-related changes in secretion of GHRH, GH and IGF-I. The basal plasma levels of GHRH and GH were not significantly different in young and elderly men, but the basal plasma level of IGF-I was higher in the young men (159.0± 11.7 vs 86.7± 11.6 μg/1). The area under the curve for plasma GH in the GHRH test was less in the elderly group (35.1 ±5.9 vs 11.2 ± 2.1 μg · h−1 · 1−1, p<0.001). The AUCs for the plasma GHRH and GH responses in the L-dopa test in young and elderly men were 32.0±2.7 vs 20.3±1.8 ng · h−1 · 1−1 (p<0.001), and 21.8±4.6 vs 5.4±1.1 μg · h−1 · 1 (p<0.01), respectively, indicating decreased releases of GHRH and GH in the elderly. Correlations between the AUCs for plasma GHRH and GH responses in L-dopa were found in both groups, but the ratio of the AUCs for GH/GHRH was lower in the elderly group. The elderly group showed a significant correlation between the basal plasma IGF-I level and the AUCs for plasma GH in the GHRH and L-dopa tests. These results suggest that elderly men have a decreased reserve of hypothalamic GHRH, resulting in secondarily impaired GH release, which may lead to a lower level of IGF-I than in young men.

Effect of actively immunizing sheep against growth hormone-releasing hormone or somatostatin on spontaneous pulsatile and neostigmine-induced growth hormone secretion

1995 ◽  
Vol 144 (1) ◽  
pp. 83-90 ◽  
Author(s):  
E Magnan ◽  
L Mazzocchi ◽  
M Cataldi ◽  
V Guillaume ◽  
A Dutour ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Physiological Role ◽  
Gh Secretion ◽  
Igf I ◽  
Plasma Gh ◽  
Hypophysial Portal

Abstract The physiological role of endogenous circulating GHreleasing hormone (GHRH) and somatostatin (SRIH) on spontaneous pulsatile and neostigmine-induced secretion of GH was investigated in adult rams actively immunized against each neuropeptide. All animals developed antibodies at concentrations sufficient for immunoneutralization of GHRH and SRIH levels in hypophysial portal blood. In the anti GHRH group, plasma GH levels were very low; the amplitude of GH pulses was strikingly reduced, although their number was unchanged. No stimulation of GH release was observed after neostigmine administration. The reduction of GH secretion was associated with a decreased body weight and a significant reduction in plasma IGF-I concentration. In the antiSRIH group, no changes in basal and pulsatile GH secretion or the GH response to neostigmine were observed as compared to controls. Body weight was not significantly altered and plasma IGF-I levels were reduced in these animals. These results suggest that in sheep, circulating SRIH (in the systemic and hypophysial portal vasculature) does not play a significant role in pulsatile and neostigmine-induced secretion of GH. The mechanisms of its influence on body weight and production of IGF-I remain to be determined. Journal of Endocrinology (1995) 144, 83–90

Relationship between plasma growth hormone concentration and cellular sodium transport in acromegaly

1992 ◽  
Vol 127 (1) ◽  
pp. 38-43 ◽  
Author(s):  
Hans Herlitz ◽  
Olof Jonsson ◽  
Bengt-Åke Bengtsson
Keyword(s):  
Growth Hormone ◽  
Sodium Transport ◽  
Negative Relationship ◽  
Sodium Content ◽  
Plasma Growth Hormone ◽  
Sodium Influx ◽  
Active Acromegaly ◽  
One Year ◽  
Plasma Gh

We investigated the relationship between mean plasma growth hormone (GH) concentration and cellular sodium transport in untreated and treated acromegaly. Seventeen patients (age 55±3 years) with active acromegaly were studied with respect to plasma GH (mean of 24 h GH profile) and erythrocyte electrolyte content as well as transmembrane sodium transport. The patients were reinvestigated two weeks after successful surgery (N=14) and again after one year (N=13). Erythrocyte electrolytes were analyzed by flame photometry and sodium influx and efflux rate constant determined by in vitro incubation using a modified Keyne's formula. In patients with active acromegaly there was a significant positive correlation between IGF-1 and cellular sodium transport, while GH tended to show a negative relationship to the same parameter. After successful treatment, both IGF-1 and GH disclosed a positive relationship to cellular sodium transport. After one year, a significant increase in erythrocyte sodium content was seen in the patients compared to the preoperative situation. In conclusion, if this is a generalized phenomenon the results are compatible with a sodium-retaining effect of GH via stimulation of transmembrane sodium transport. In active acromegaly this may be counteracted by a sodium transport inhibitor giving the reverse relationship between GH and cellular sodium transport.

scholarly journals Treatment With Recombinant Igf-I for Patients With Growth Hormone (Gh) Gene Deletions

1997 ◽  
Vol 41 (2) ◽  
pp. 301-301
Author(s):  
S B Oliveira ◽  
I J P Arnhold ◽  
J A Phillips ◽  
B B Mendonça
Keyword(s):  
Growth Hormone ◽  
Gene Deletions ◽  
Igf I ◽  
Gh Gene ◽  
Gh Gene Deletions

Somatostatin tonically inhibits growth hormone secretion in domestic fowl

1986 ◽  
Vol 111 (1) ◽  
pp. 91-97 ◽  
Author(s):  
S. Harvey ◽  
S.-K. Lam ◽  
T. R. Hall
Keyword(s):  
Growth Hormone ◽  
Domestic Fowl ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Passive Immunization ◽  
Inhibitory Effect ◽  
Gh Secretion ◽  
Basal Plasma ◽  
Plasma Gh

ABSTRACT Passive immunization of immature chickens with sheep somatostatin (SRIF) antiserum promptly increased the basal plasma GH concentration and augmented TRH-induced GH secretion. Although exogenous SRIF had no inhibitory effect on the basal GH concentration in untreated birds or birds pretreated with non-immune sheep serum, it suppressed the stimulatory effect of SRIF immunoneutralization on GH secretion. These results suggest that SRIF is physiologically involved in the control of GH secretion in birds, in which it appears to inhibit GH release tonically. J. Endocr. (1986) 111, 91–97

scholarly journals Treatment With Recombinant Igf-I for Patients With Growth Hormone (Gh) Gene Deletions. 37

1998 ◽  
Vol 43 (2) ◽  
pp. 301-301
Author(s):  
S B Oliveira ◽  
J P Arnhold ◽  
J A Phillips ◽  
B B Mendonca
Keyword(s):  
Growth Hormone ◽  
Gene Deletions ◽  
Igf I ◽  
Gh Gene ◽  
Gh Gene Deletions

scholarly journals Reduced disorderliness of growth hormone release in biochemically inactive acromegaly after pituitary surgery

1998 ◽  
pp. 164-169 ◽  
Author(s):  
G van den Berg ◽  
SM Pincus ◽  
M Frolich ◽  
JD Veldhuis ◽  
F Roelfsema
Keyword(s):  
Approximate Entropy ◽  
Pituitary Surgery ◽  
Early Recurrence ◽  
Gh Secretion ◽  
Control Subjects ◽  
Pituitary Dysfunction ◽  
Igf I ◽  
Active Acromegaly ◽  
Plasma Gh ◽  
Igfbp 3

The episodicity of 24 h GH release was studied in 18 patients with active acromegaly, 12 patients 7-10 days after pituitary surgery, 14 patients long after operation (3-17 years), and 21 healthy gender- and age-matched control subjects, using a recently introduced scale- and model-independent regularity statistic, approximate entropy (ApEn). Blood samples were taken at 10-min intervals for 24 h, and plasma GH concentrations were measured by immunofluorometric assay (detection limit 11.5 ng/l). For this study we selected operated patients who were biochemically in remission, defined by normal circulating IGF-I and insulin-like growth factor-binding protein-3 (IGFBP-3) concentrations, normal glucose-suppressed plasma GH concentration (<0.38 microg/l), and the normalization of the paradoxical rise of GH to TRH or GnRH. In patients with active acromegaly ApEn was 1.23+/-0.04, with no overlap with the control subjects (P = 1.2 x 10[-16]), who had an ApEn of 0.40+/-0.04. ApEn in patients shortly after surgery was 0.71+/-0.09 (P < 0.001 vs controls), and long after surgery 0.56+/-0.05 (P < 0.011 vs controls). ApEn values in treated and untreated patients correlated significantly with the plasma concentration of IGF-I (r=0.531) and IGFBP-3 (r=0.598), and the log-transformed 24h GH secretion rate (r=0.749). Shortly after surgery only one-third of the patients had a normal ApEn value, whereas long after surgery about 70% of the patients had a normal ApEn value. Although ApEn eventually normalized in about 70% of the operated patients, the cause of the persistence of abnormal GH release in the remainder of the subjects is not known, and might reflect permanent hypothalamic-pituitary dysfunction or a very early recurrence of the somatotroph adenoma.

scholarly journals Genetic characterization of short stature patients with overlapping features of growth hormone insensitivity syndromes

2021 ◽  
Author(s):  
Afiya Andrews ◽  
Avinaash Maharaj ◽  
Emily Cottrell ◽  
Sumana Chatterjee ◽  
Pratik Shah ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Genetic Characterization ◽  
Elevated Serum ◽  
Comparative Genomic ◽  
Chromosome 11P15 ◽  
Wide Range ◽  
Igf I ◽  
Growth Hormone Insensitivity

Abstract Context and objective Growth hormone insensitivity (GHI) in children is characterized by short stature, functional IGF-I deficiency and normal or elevated serum GH concentrations. The clinical and genetic etiology of GHI is expanding. We undertook genetic characterization of short stature patients referred with suspected GHI and features which overlapped with known GH-IGF-I axis defects. Design and methods Between 2008 and 2020, our center received 149 GHI referrals for genetic testing. Genetic analysis utilized a combination of candidate gene sequencing (CGS), whole exome sequencing (WES), array comparative genomic hybridization (aCGH) and a targeted whole genome short stature gene panel. Results Genetic diagnoses were identified in 80/149 subjects (54%) with 45/80 (56%) having known GH-IGF-I axis defects (GHR n=40, IGFALS n=4, IGFIR n=1). The remaining 35/80 (44%) had diagnoses of 3M syndrome (n=10) (OBSL1 n=7, CUL7 n=2 and CCDC8 n=1), Noonan syndrome (n=4) (PTPN11 n=2, SOS1 n=1 and SOS2 n=1), Silver-Russell syndrome (n=2) (Loss of methylation on chromosome 11p15 and uniparental disomy for chromosome 7), Class 3-5 copy number variations (n=10) and disorders not previously associated with GHI (n=9) (Barth syndrome, Autoimmune lymphoproliferative syndrome, Microcephalic osteodysplastic primordial dwarfism Type II, Achondroplasia, Glycogen storage disease Type IXb, Lysinuric protein intolerance, Multiminicore Disease, MACS syndrome and Bloom syndrome). Conclusion We report the wide range of diagnoses in 149 patients referred with suspected GHI, which emphasizes the need to recognize GHI as a spectrum of clinical entities in undiagnosed short stature patients. Detailed clinical and genetic assessment may identify a diagnosis and inform clinical management.

Growth and growth hormone kinetics in Holstein steer calves

1993 ◽  
Vol 73 (2) ◽  
pp. 277-285 ◽  
Author(s):  
G. J. Mears ◽  
G. B. Schaalje
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Average Daily Gain ◽  
Volume Of Distribution ◽  
Canola Meal ◽  
Metabolic Clearance ◽  
Grass Hay ◽  
Basal Plasma ◽  
Rumen Undegradable Protein ◽  
Plasma Gh

Average daily gain (ADG), basal plasma growth hormone (GH) concentration, and plasma GH kinetics following a bolus injection of GH were determined at birth and at 75, 150, 250, 350 and 450 kg body weight in 19 Holstein steer calves. From 100 kg body weight, calves were fed one of three diets: 85% grass hay and 15% concentrate; 85% grass hay and 15% concentrate with rumen undegradable protein (formaldehyde-treated canola meal); and, 85% concentrate and 15% grass hay. Addition of rumen undegradable protein to the hay-based diet did not (P > 0.05) increase ADG. However, ADG were higher (P < 0.001) for calves on the 85% concentrate diet. Calf basal plasma GH concentrations, plasma GH clearance rates, and GH secretion rates were not affected by either diet or ADG adjusted for the effect of diet. In contrast, body weight had a large effect on basal plasma GH concentration and plasma GH kinetics. As body weight increased, basal plasma GH concentration and GH half-life decreased. Growth hormone steady state volume of distribution, metabolic clearance rate and secretion rate per kg of body weight all decreased as calves became heavier. Key words: Steer growth, growth hormone, GH, basal GH, clearance, secretion

scholarly journals Large body size in the dog is associated with transient GH excess at a young age

2001 ◽  
Vol 170 (2) ◽  
pp. 479-484 ◽  
Author(s):  
RP Favier ◽  
JA Mol ◽  
HS Kooistra ◽  
A Rijnberk
Keyword(s):  
Body Size ◽  
Large Body ◽  
Young Age ◽  
Adult Body Size ◽  
Significant Difference ◽  
Adult Body ◽  
Igf I ◽  
Basal Plasma ◽  
The Mean ◽  
Plasma Gh

The main determinants of body size are GH and IGFs. The aim of this study was to investigate whether differences in adult body size of medium-sized and giant dog breeds can be explained by differences in GH release and/or in plasma IGF-I and IGF-II concentrations at a young age. The basal plasma concentrations of GH, IGF-I and IGF-II were determined once weekly in six Great Danes and six beagles from the age of 6 weeks until the age of 24 weeks. In addition, the 6 h secretory profile of GH was determined every 2 weeks. Basal plasma GH concentrations as well as the total area under the curve (AUC) and the AUC above the baseline for GH were significantly higher in Great Danes than in beagles of the same age. In contrast, plasma IGF-I and IGF-II concentrations did not differ significantly between the two breeds. Compared with values in adults, the basal plasma GH concentrations were high until the age of 7 weeks in the beagles, whereas in the Great Danes the basal plasma GH levels remained high during the entire observation period, albeit with a gradual decline. The mean frequency and the mean amplitude of GH pulses tended to be higher in Great Danes than in beagles, although a significant difference was only reached at the age of 19 and 23 weeks for the frequency and at the ages of 9, 11 and 13 weeks for the amplitude. An age-dependent decrease in pulse frequency occurred in the Great Danes. The results of this study demonstrate that differences in adult body size of medium-sized and giant dog breeds are preceded by differences in GH release and not by differences in circulating IGF-I or IGF-II concentrations. Both young Great Danes and young beagles experience a period of high GH release, but this period persists much longer in Great Danes. It is discussed that this difference may be due to delayed maturation of the inhibitory influences of somatostatin on pituitary GH release in the latter dogs.

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