Secretion of growth hormone-releasing hormone in patients with idiopathic pituitary dwarfism and acromegaly

1988 ◽  
Vol 117 (2) ◽  
pp. 273-281 ◽  
Author(s):  
Ryuichi Yamasaki ◽  
Haruhiko Saito ◽  
Kazuhito Kameyama ◽  
Eiji Hosoi ◽  
Shiro Saito
Keyword(s):  
Type I ◽  
Normal Children ◽  
Pituitary Dwarfism ◽  
Gh Secretion ◽  
Fasting Plasma ◽  
Pathophysiological Role ◽  
Plasma Gh ◽  
High Level ◽  
Normal Adults

Abstract. The plasma levels of immunoreactive-GHRH in patients with idiopathic pituitary dwarfism and acromegaly were studied in the basal state and during various tests by a sensitive and specific RIA. The fasting plasma GHRH level in 22 patients with idiopathic pituitary dwarfism was 6.3 ± 2.3 ng/l (mean ± sd), which was significantly lower than that in normal children (9.8 ± 2.8 ng/l, N = 21), and eight of them had undetectable concentrations (less than 4.0 ng/l). Little or no response of plasma GHRH to oral administration of L-dopa was observed in 7 of 10 pituitary dwarfs, and 3 of the 7 patients showed a response of plasma GH to iv administration of GHRH (1 μg/kg). These findings suggest that one of the causes of idiopathic pituitary dwarfism is insufficient GHRH release from the hypothalamus. The fasting plasma GHRH level in 14 patients with acromegaly and one patient with gigantism was 8.0 ± 3.9 ng/l, which was slightly lower than that in normal adults (10.4 ± 4.1 ng/l, N = 72). One acromegalic patient with multiple endocrine neoplasia type I had a high level of plasma GHRH (270 ng/l) with no change in response to L-dopa and TRH test. In 3 untreated patients with acromegaly L-dopa did not induce any response of plasma GHRH in spite of inconsistent GH release, and in 4 patients with acromegaly, TRH evoked no response of plasma GHRH in spite of a marked GH release, suggesting that the GH responses are not mediated by hypothalamic GHRH. These findings suggest that the measurement of plasma GHRH in response to L-dopa with a sensitive and specific RIA could be of use in clarifying the pathophysiological role of endogenous GHRH in patients with GH secretion disorders.

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

Cholinergic modulation of GH secretion in acromegalic patients before and after pituitary surgery

1992 ◽  
Vol 127 (6) ◽  
pp. 489-493 ◽  
Author(s):  
Leon Fiszlejder ◽  
Olga Penacini ◽  
Susana Ratz ◽  
Adriana Oneto ◽  
Maria Storani ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Pituitary Surgery ◽  
Normal Subjects ◽  
Physiological Control ◽  
Gh Secretion ◽  
Pathophysiological Role ◽  
Before And After ◽  
Transsphenoidal Adenomectomy ◽  
Ghrh Test

Cholinergic neurotransmission exerts a physiological control on GH secretion. Pirenzepine (Pz), an antagonist of muscarinic receptors, by enhancing hypothalamic somatostatin release, inhibits stimulated GH secretion in normal subjects but not in acromegalic patients. To address the hypothesis that a feedback effect of GH hypersecretion can be involved in this condition, GH responses to GHRH 1–29, 1 μg/kg iv, with and without administration of Pz, 40mg iv before tests, were investigated in eight acromegalic patients, before and 20–30 days after transsphenoidal adenomectomy. Pz diminished (p<0.001) the incremental area under the curve (AUC) of GH responses to GHRH in seven normal controls. In contrast, GHRH responsiveness in untreated acromegalic patients was not affected by Pz. Postoperative basal GH levels decreased by 62.4±14.9% (p<0.01). Pz inhibited GH responses to GHRH (p<0.01). Furthermore, a direct relationship (r = 0.73, p<0.01) between basal concentrations and the AUC of GH responses following Pz plus GHRH-test was found. The finding that muscarinic receptor activity recovered after the reduction of serum GH basal levels by pituitary surgery lends support to the proposed pathophysiological role of GH excess as a possible determinant factor in cholinergicsomatostatinergic dysfunction in acromegaly.

The role of somatostatin and/or dopamine in basal and TRH-stimulated TSH release in food-restricted rats

1991 ◽  
Vol 125 (2) ◽  
pp. 186-191 ◽  
Author(s):  
Felipe Rodriguez ◽  
Trinidad Jolin
Keyword(s):  
Rabbit Serum ◽  
Dopamine Antagonists ◽  
Normal Rabbit Serum ◽  
Restricted Feeding ◽  
Gh Secretion ◽  
Endogenous Dopamine ◽  
Tsh Secretion ◽  
Anterior Pituitary Function ◽  
Plasma Gh

Abstract. The present study was carried out to examine the role of endogenous dopamine and somatostatin in the mechanisms involved in the restricted feeding-induced inhibition of TSH secretion in rats. GH secretion was examined in parallel. Restricted feeding by 50% or 75% was associated with a decrease in the pituitary and circulating levels of TSH and GH in both untreated and TRH-treated groups (p<0.001), the changes being proportional to the feeding level. Intravenous injections of the dopamine antagonists, domperidone or haloperidol, failed to affect the magnitude of the differences in plasma TSH and GH levels among control and food-restricted groups, indicating that dopaminergic mechanisms had little effect on the regulation of TSH and GH secretion during restricted feeding in rats. Cerebroventricular injection of somatostatin anti-serum resulted in a marked increase in plasma TSH and GH levels in all the experimental groups (p<0.001). The increase in plasma GH and TSH induced by somatostatin anti-serum was greater in rats fed a 25% diet than in either controls or rats fed 50% of the diet; the values for the latter two groups were also different (p<0.001). The decreased TSH and GH values in somatostatin anti-serum-treated food restricted rats as compared with those in control animals on somatostatin anti-serum or normal rabbit serum can probably be attributed to the decreased available pituitary TSH and GH pools. The data indicate that long-term restricted feeding affects anterior pituitary function in rats, presumably reflecting alterations in the secretion of an inhibiting hormone, somatostatin.

The role of prolactin in the inhibitory action of bromocriptine on growth hormone secretion in acromegaly

1983 ◽  
Vol 103 (4) ◽  
pp. 446-450 ◽  
Author(s):  
S. W. J. Lamberts ◽  
J. G. M. Klijn ◽  
C. C. J. van Vroonhoven ◽  
S. Z. Stefanko ◽  
A. Liuzzi
Keyword(s):  
Pituitary Adenomas ◽  
Inhibitory Action ◽  
Growth Hormone Secretion ◽  
Pituitary Tumour ◽  
Tumour Tissue ◽  
Simultaneous Presence ◽  
Gh Secretion ◽  
Plasma Gh ◽  
Plasma Prl

Abstract. Bromocriptine treatment results in clinical improvement and inhibition of plasma GH levels in only part of the acromegalic patients. The possible role of the simultaneous presence of Prl and GH in GH-secreting pituitary adenomas was investigated with regard to the inhibitory action of bromocriptine on GH secretion and the paradoxical increase of GH release in reaction to TRH. Surgically obtained pituitary tumour tissue from 35 consecutive acromegalic patients was studied immunohistochemically. In 21 patients no Prl was present in the tumour tissue. These patients had normal plasma Prl levels. In the other 14 patients Prl was present in the tumour tissue. Hyperprolactinaemia was found in 10 of these 14 patients. Plasma GH levels from 2 till 10 h after the administration of 2.5 mg bromocriptine measured before operation were significantly more suppressed in the patients with mixed GH/Prl-containing than in those with pure GH-containing pituitary adenomas, being 38 ± 4% and 65 ± 4% of basal values, respectively (P< 0.01). The response of GH to TRH, however, did not differ significantly between the two groups. Conclusions: 1. In about 70% of patients with 'mixed' GH/Prl containing adenomas, hyperprolactinaemia is present. 2. The simultaneous presence of Prl and GH in a GH-secreting pituitary tumour increases the sensitivity of GH secretion to bromocriptine. 3. The plasma Prl level is of value to predict which patients with acromegaly are likely to respond to bromocriptine with an inhibition of GH secretion.

Diurnal Variations of Plasma Growth Hormone and Brain Monoamines in Adult Male Rats

1973 ◽  
Vol 51 (12) ◽  
pp. 890-892 ◽  
Author(s):  
R. Collu ◽  
J. C. Jéquier ◽  
J. Letarte ◽  
G. Leboeuf ◽  
J. R. Ducharme
Keyword(s):  
Growth Hormone ◽  
Adult Male ◽  
Physiological Role ◽  
Male Rats ◽  
Male Rat ◽  
Plasma Growth Hormone ◽  
Gh Secretion ◽  
Adult Male Rat ◽  
Plasma Gh

Brain levels of monoamines (MA) in the adult male rat show a diurnal pattern of secretion with noradrenaline (NA) and serotonin (5-HT) reaching a peak at 1300 and 1800, respectively, and dopamine (DA) showing a bimodal pattern with peaks at 0500 and 1800. Plasma growth hormone (GH) values fluctuate widely during the nycthemeral period. Statistically significant correlations between plasma GH and brain MA levels, confirming the existence of a physiological role of MA in the control of GH secretion, could not be demonstrated in the present study.

Rapid changes in growth hormone regulation and hypothalamic somatostatin after transection of anterolateral pathways to the medial-basal hypothalamus in the rat

1985 ◽  
Vol 104 (1) ◽  
pp. 121-127 ◽  
Author(s):  
I. Kakucska ◽  
M. Antal ◽  
M. Kárteszi ◽  
G. B. Makara
Keyword(s):  
Median Eminence ◽  
Hormone Regulation ◽  
High Concentration ◽  
Medial Basal Hypothalamus ◽  
Control Value ◽  
Gh Secretion ◽  
Gh Cells ◽  
Plasma Gh ◽  
High Level

ABSTRACT Plasma and pituitary GH content, in-vitro GH release and somatostatin-like immunoreactivity (SLI) in the stalk-median eminence were studied up to 7 days after making an anterolateral cut (ALC) around the medial-basal hypothalamus. Plasma GH concentration increased within 15 min to a very high level, then fell to a high level which was unchanged for several hours. The GH concentration then steadily decreased between days 2 and 7. The SLI content in the stalk-median eminence decreased to 3·5% of the control value within 3 days. The GH content of the anterior pituitary gland was 58·8% of the control value by 1 week after the operation but the in-vitro sensitivity to somatostatin of the GH cells failed to change. Pentobarbitone injection stimulated GH release in the sham-operated controls but decreased it in the rats with an ALC. These findings suggest that transection of somatostatin-containing fibres is followed by a rapid rise and a lasting high concentration of plasma GH which slowly returns towards lower levels in parallel with a marked depletion of pituitary GH content. In rats with transected somatostatin innervation of the median eminence, sodium pentobarbitone probably decreases GH secretion by depressing the secretion of GH-releasing hormone. J. Endocr. (1985) 104, 121–127

Synthetic peptide-based immunoassay for amino-terminal propeptide of type I procollagen: application for evaluation of bone formation

1993 ◽  
Vol 39 (11) ◽  
pp. 2254-2258 ◽  
Author(s):  
S G Linkhart ◽  
T A Linkhart ◽  
A K Taylor ◽  
J E Wergedal ◽  
P Bettica ◽  
...  
Keyword(s):  
Bone Formation ◽  
Synthetic Peptide ◽  
Type I ◽  
Normal Children ◽  
Amino Acid Peptide ◽  
Amino Terminal ◽  
Type I Procollagen ◽  
Serum Biochemical ◽  
Alkaline Phosphatase Isoenzyme ◽  
Normal Adults

Abstract Serum biochemical markers are powerful tools for the evaluation of bone turnover. In this study, we developed a radioimmunoassay, using a synthetic peptide for the N-terminal fragment of human type I [alpha 1(I)] procollagen (N-PCP). A 14-amino acid peptide was synthesized from the amino terminus and used to generate antibodies in rabbits. The synthetic peptide was used as standard and tracer in the assay. Both native type I amino procollagen (PINP), which was purified from skin fibroblasts, and human serum displaced tracer binding in parallel with the synthetic peptide. The range for measurement of N-PCP in serum was 0.7 to 30 micrograms/L (0.21-9.18 nmol/L). In a sample of 17 normal adults and 13 children (ages 9-16 years) there was a strong correlation between serum N-PCP determined by this assay and both skeletal alkaline phosphatase isoenzyme and osteocalcin, markers of bone formation. Serum concentrations of N-PCP in a group of normal children were eightfold higher than concentrations in normal adults, with no overlap between the two groups. N-PCP also correlated with C-terminal type I procollagen determined with a commercially available kit (r = 0.92).

scholarly journals Hepatitis C Virus Escape Studies of Human Antibody AR3A Reveal a High Barrier to Resistance and Novel Insights on Viral Antibody Evasion Mechanisms

2018 ◽  
Vol 93 (4) ◽  
Author(s):  
Rodrigo Velázquez-Moctezuma ◽  
Andrea Galli ◽  
Mansun Law ◽  
Jens Bukh ◽  
Jannick Prentoe
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Vaccine Development ◽  
Scavenger Receptor ◽  
Hypervariable Region ◽  
Type I ◽  
Low Level ◽  
Class B ◽  
High Level

ABSTRACTYearly, ∼2 million people become hepatitis C virus (HCV) infected, resulting in an elevated lifetime risk for severe liver-related chronic illnesses. Characterizing epitopes of broadly neutralizing antibodies (NAbs), such as AR3A, is critical to guide vaccine development. Previously identified alanine substitutions that can reduce AR3A binding to expressed H77 envelope were introduced into chimeric cell culture-infectious HCV recombinants (HCVcc) H77(core-NS2)/JFH1. Substitutions G523A, G530A, and D535A greatly reduced fitness, and S424A, P525A, and N540A, although viable, conferred only low-level AR3A resistance. Using highly NAb-sensitive hypervariable region 1 (HVR1)-deleted HCVcc, H77/JFH1ΔHVR1and J6(core-NS2)/JFH1ΔHVR1, we previously reported a low barrier to developing AR5A NAb resistance substitutions. Here, we cultured Huh7.5 cells infected with H77/JFH1, H77/JFH1ΔHVR1, or J6/JFH1ΔHVR1with AR3A. We identified the resistance envelope substitutions M345T in H77/JFH1, L438S and F442Y in H77/JFH1ΔHVR1, and D431G in J6/JFH1ΔHVR1. M345T increased infectivity and conferred low-level AR3A resistance to H77/JFH1 but not H77/JFH1ΔHVR1. L438S and F442Y conferred high-level AR3A resistance to H77/JFH1ΔHVR1but abrogated the infectivity of H77/JFH1. D431G conferred AR3A resistance to J6/JFH1ΔHVR1but not J6/JFH1. This was possibly because D431G conferred broadly increased neutralization sensitivity to J6/JFH1D431Gbut not J6/JFH1ΔHVR1/D431Gwhile decreasing scavenger receptor class B type I coreceptor dependency. Common substitutions at positions 431 and 442 did not confer high-level resistance in other genotype 2a recombinants [JFH1 or T9(core-NS2)/JFH1]. Although the data indicate that AR3A has a high barrier to resistance, our approach permitted identification of low-level resistance substitutions. Also, the HVR1-dependent effects on AR3A resistance substitutions suggest a complex role of HVR1 in virus escape and receptor usage, with important implications for HCV vaccine development.IMPORTANCEHepatitis C virus (HCV) is a leading cause of liver-related mortality, and limited treatment accessibility makes vaccine development a high priority. The vaccine-relevant cross-genotype-reactive antibody AR3A has shown high potency, but the ability of the virus to rapidly escape by mutating the AR3A epitope (barrier to resistance) remains unexplored. Here, we succeeded in inducing only low-level AR3A resistance, indicating a higher barrier to resistance than what we have previously reported for AR5A. Furthermore, we identify AR3A resistance substitutions that have hypervariable region 1 (HVR1)-dependent effects on HCV viability and on broad neutralization sensitivity. One of these substitutions increased envelope breathing and decreased scavenger receptor class B type I HCV coreceptor dependency, both in an HVR1-dependent fashion. Thus, we identify novel AR3A-specific resistance substitutions and the role of HVR1 in protecting HCV from AR3-targeting antibodies. These viral escape mechanisms should be taken into consideration in future HCV vaccine development.

scholarly journals Pathophysiological role of secretory type I and II phospholipase A2 in acute pancreatitis: an experimental study in rats.

Gut ◽  
1997 ◽  
Vol 40 (3) ◽  
pp. 386-392 ◽  
Author(s):  
W Uhl ◽  
H J Schrag ◽  
N Schmitter ◽  
T J Nevalainen ◽  
J Aufenanger ◽  
...  
Keyword(s):  
Experimental Study ◽  
Acute Pancreatitis ◽  
Phospholipase A2 ◽  
Type I ◽  
Pathophysiological Role ◽  
Secretory Type

Measurement of nocturnal urinary growth hormone values

1989 ◽  
Vol 121 (2) ◽  
pp. 290-296 ◽  
Author(s):  
Izumi Sukegawa ◽  
Naomi Hizuka ◽  
Kazue Takano ◽  
Kumiko Asakawa ◽  
Reiko Horikawa ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Turner's Syndrome ◽  
Turner’S Syndrome ◽  
Gh Secretion ◽  
Short Children ◽  
The Mean ◽  
Plasma Gh ◽  
Normal Adults ◽  
Collection Time

Abstract. Nocturnal urinary growth hormone values were measured by a sensitive enzyme immunoassay in normal adults, patients with GH deficiency, patients with Turner's syndrome, normal but short children who had normal plasma GH responses to provocative tests, and patients with acromegaly. The mean nocturnal urinary GH values in patients with acromegaly were significantly greater than those in normal adults (1582.3 ± 579.8 vs 53.5 ± 8.6 pmol/mmol creatinine (± sem); p < 0.05). In the normal but short children and patients with Turner's syndrome, the mean nocturnal urinary GH values were 83.1 ± 5.2 and 79.8 ± 29.5 pmol/mmol creatinine, respectively. In patients with GH deficiency, the nocturnal urinary GH values were undetectable (< 5.3 pmol/mmol creatinine) except in one patient where the value was 6.3 pmol/mmol creatinine. The nocturnal urinary GH values of the patients with GH deficiency were significantly lower than those of the other groups (p < 0.05). In normal but short children, the nocturnal urinary GH values correlated significantly with mean plasma nocturnal GH concentrations (r = 0.76, p < 0.001), and 24-hour urinary GH values (r = 0.84, p < 0.001), respectively. In 4 patients with GH deficiency who had circulating anti-hGH antibody, the urinary GH values were also undectable. These data indicate that nocturnal urinary GH value reflects endogenous GH secretion during collection time, and that measurement of the nocturnal urinary GH values is a useful method for screening of patients with GH deficiency and acromegaly.

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