Influence of Dopaminergic, Adrenergic and Cholinergic Blockade and TRH Administration on Gh Responses to GRF 1–29

Jordan, Vanessa; Diéguez, Carlos; Lafaffian, I.; Rodríguez-Arnao, M. D.; Gómez-Pan, A.; Hall, R.; Scanlon, M. F.

doi:10.1111/j.1365-2265.1986.tb03270.x

Cited by 53 publications

(28 citation statements)

References 36 publications

(10 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In apparent conflict with our findings, Jordan et al [20], using similar doses and mode of drug administration, have re ported that MCP did not change the GH response to GHRH in any way. The wide range of GHRH-induced GH peaks shown in this study [20] indicates a nonuniform distribution of the HSR phases at the time of GHRH testing; and perhaps this is the explanation for the lack of effects of MCP observed by this group.…”

Section: Discussioncontrasting

confidence: 56%

“…The wide range of GHRH-induced GH peaks shown in this study [20] indicates a nonuniform distribution of the HSR phases at the time of GHRH testing; and perhaps this is the explanation for the lack of effects of MCP observed by this group. In fact, this also was observed in the present study when the GHRH challenge took place during a spontaneous se cretory phase.…”

Section: Discussionmentioning

confidence: 82%

See 1 more Smart Citation

Role of Central Dopaminergic Pathways in the Neural Control of Growth Hormone Secretion in Normal Men: Studies with Metoclopramide

et al. 1991

View full text Add to dashboard Cite

The aim of this study was to gain further insight into the role that central dopaminergic pathways play in GH neuroregulation in man. Our experimental hypothesis was based on the possibility that most of the controversies on DA role could be due to the fact that the hypothalamic somatotroph rhythm (HSR) was not taken into account when interpreting the GH responses after pharmacological manipulations on dopaminergic pathways. In 10 normal subjects we monitored the effect of central dopaminergic blockade, achieved with metoclopramide (MCP; 10 mg, i.v. bolus), on the pattern of spontaneous GH secretion and the GH responses to a GHRH challenge (GRF_1–29, 1 µg/kg, i.v. bolus) administered together with MCP or 60 min after this drug was given. The study of HSR was made according to our previous postulate. Our results indicate that MCP administration, either prior to or together with the GHRH bolus, significantly increased GHRH-induced GH release during a refractory HSR phase; but not when the GHRH challenge took place during a spontaneous secretory phase. The strong relationship between pre-GHRH plasma GH values and GHRH-elicited GH peaks was lost when MCP was given. These data indicate that MCP was able to disrupt the intrinsic HSR by inhibiting the hypothalamic release of somatostatin (SS). While a main conclusion would be that central DA is a secretagogue for SS secretion, our results also suggest that this role could be dependent on its effects on the adrenergic inputs to SS neurons.

show abstract

Section: Discussioncontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 82%

Role of Central Dopaminergic Pathways in the Neural Control of Growth Hormone Secretion in Normal Men: Studies with Metoclopramide

et al. 1991

View full text Add to dashboard Cite

show abstract

“…Pyridostigmine does not cross the blood-brain barrier and thus may be presumed to act either at the median eminence or at the level of the pituitary. An effect of pyri¬ dostigmine to increase endogenous GHRH release is unlikely, as cholinergic antagonists abolish the GH response to GHRH (18,19,(27)(28)(29)(30)(31), and pyri¬ dostigmine enhances the GH response to supramaximal doses of GHRH (21). The effect of cho¬ linergic drugs on pituitary GH release is contro¬ versial.…”

Section: Discussionmentioning

confidence: 95%

Pyridostigmine enhances, but does not normalise, the GH response to GH-releasing hormone in obese subjects

Castro

Vieira²,

Chacra³

et al. 1990

Acta Endocrinologica

View full text Add to dashboard Cite

Obese patients are characterised by several neuroendocrine abnormalities, including characteristically a decrease in growth hormone responsiveness to GH-releasing hormone. In normal subjects, the GH response to GHRH is enhanced by the acetylcholinesterase inhibitor, pyridostigmine. We have studied the effect of this drug on GH secretion in gross obesity. Twelve obese patients were studied (mean weight 156% of ideal) and compared with a group of 8 normal volunteers. Each subject was initially studied on two occasions, in random order, with GHRH (1-29) NH2 100 \g=m\g iv alone and following pretreatment with pyridostigmine 120 mg orally one hour prior to GHRH. In obese patients, the GH response to GHRH was significantly blunted when compared to controls (GH peak: 20 \ m=+-\4 vs 44 \m=+-\16 \g=m\g/l ; mean \ m=+-\ sem). After pyridostigmine, the response to GHRH was enhanced in the obese subjects, but remained significantly reduced compared to non-obese subjects treated with GHRH and pyridostigmine (GH peak: 30 \ m=+-\5 vs 77 \ m=+-\20 \g=m\g/l ,respectively). In 6 subjects, higher doses of GHRH or pyridostigmine did not further increase GH responsiveness in obese patients. Our results suggest that obese patients have a disturbed cholinergic control of GH release, probably resulting from increased somatostatinergic tone. This disturbed regulation may be responsible, at least in part, for the blunted GH responses to provocative stimuli.Obese patients have blunted growth hormone re¬ sponses to a wide variety of stimuli (1-8). It has also been shown that these patients have decreased GH responses to GH-releasing hormone (9-14). This could be due to reduced pituitary sensitivity to GHRH, excess of hypothalamic somatostatin, or a chronic state of GHRH deficiency. Several lines of evidence point to a role for somatostatin in the de¬ creased GH release found in obesity. Obese pa¬ tients have blunted thyroid stimulating hormone response to TSH-releasing hormone (15), which might also reflect an increase in somatostatinergic tone. Furthermore, genetically-obese rats have in¬ creased hypothalamic somatostatin content (16) and increased hypothalamic somatostatin release in vitro (17). However, there is little direct evidence in the human.Pyridostigmine is a drug which activates cholinergic receptors by decreasing the activity of acetylcholinesterase, and enhances GH responsiveness to ; this is considered to occur via the inhibition of hypothalamic somatostatin (22). Recent studies have suggested that pyridostigmine may increase the GH response to GHRH in obesity, but only single doses of the drug were used, which did not take into account the increased body weight of the obese group compared to the controls (23,24).In order to investigate whether hypothalamic so¬ matostatin activity is increased in obesity, we have therefore studied the effect of several doses of py¬ ridostigmine on the GH response to GHRH in obese patients.

show abstract

“…GH, PRL and insulin were measured by radioimmuno-assay as previously described [8,9]. Insulin-like growth factor 1 (IGF-1) levels were kindly measured by Prof. M. Preece at the Institute of Child Health, Lon don.…”

Section: Assay Methodologymentioning

confidence: 99%

Long-Term Treatment of Acromegaly with Octreotide (Sandostatin)

Page

Millward²,

Hourihan³

et al. 1990

Horm Res

Self Cite

View full text Add to dashboard Cite

Sixteen patients with acromegaly have been treated with octreotide [ 100 µg twice daily to 200 µg 3 times daily according to growth hormone (GH) response] for between 3 and 44 months. The mean serum GH concentrations fell from 39.3 mU/1 before treatment to 10.5 mU/1 on day 1 of treatment and, with continued treatment (and higher doses in 8 of 16 patients), to 7.9 mU/1. In 2 patients there was no GH suppression. GH suppression after the first administration of octreotide appeared to predict long-term response. Pre-treatment serum insulin-like growth factor 1 levels were elevated in 11 of 12 patients investigated, but were normalized on continued octreotide therapy in 10 of 12. Octreotide suppressed prolactin secretion in all 6 hyperprolactinaemic patients. Steatorrhoea occurred in 15 of 16 patients at initiation of treatment, but resolved in all within 7 days. Two patients developed gallstones. In summary, octreotide is a safe and effective treatment for acromegaly, producing clinical and biochemical improvement in up to 90% of patients. Octreotide is a valuable adjunctive treatment where surgery has failed and also in those with contra-indications to surgery.

show abstract

Influence of Dopaminergic, Adrenergic and Cholinergic Blockade and TRH Administration on Gh Responses to GRF 1–29

Cited by 53 publications

References 36 publications

Role of Central Dopaminergic Pathways in the Neural Control of Growth Hormone Secretion in Normal Men: Studies with Metoclopramide

Role of Central Dopaminergic Pathways in the Neural Control of Growth Hormone Secretion in Normal Men: Studies with Metoclopramide

Pyridostigmine enhances, but does not normalise, the GH response to GH-releasing hormone in obese subjects

Long-Term Treatment of Acromegaly with Octreotide (Sandostatin)

Contact Info

Product

Resources

About