Growth Hormone (GH)-Releasing Activity of TRH and GH-Lowering Effect of Dopaminergic Drugs in Acromegaly: Homogeneity in the Two Responses

Liuzzi, Antonio; Chiodini, P. G.; Botalla, L; Silvestrini, F; Müller, E. E.

doi:10.1210/jcem-39-5-871

Cited by 126 publications

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“…The results of this work clearly show that acutely administered rhEPO has no in¯uence on GH responses to TRH stimulation in a group of acromegalic patients, with 12 out of 16 subjects exhibiting a GH increase of at least twice the basal level when tested with TRH alone (2). As in other studies, the variability in the GH responses to TRH may be accounted for by the intrinsic secretory characteristics of each adenoma (14).…”

Section: Discussionsupporting

confidence: 57%

“…A paradoxical response of GH in the TRH test was considered to be present when the GH concentration increased > 100% from baseline values (2). According to this criterion, all but four patients exhibited paradoxical GH reactions after TRH injection.…”

Section: Growth Hormone Responsesmentioning

confidence: 99%

“…Some of the alterations found in acromegaly include the incomplete suppression of GH levels after glucose loading (1), a decrease after administration of L-dopa (2) or galanin (3), and the so-called paradoxical responses to stimuli (such as thyrotropin-releasing hormone (TRH) (2,4), gonadotropin-releasing hormone (GnRH) (5) and corticotropin-releasing hormone (CRH) (6)) that do not release GH in normal subjects.…”

Section: Introductionmentioning

confidence: 99%

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Effects of acute infusion of erythropoietin on paradoxical responses of growth hormone to thyrotropin-releasing hormone in acromegalic patients

Iglesias²,

Sastre³

et al. 2000

European Journal of Endocrinology

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Objective: Our aim has been to evaluate the effects of i.v. infusion of recombinant human erythropoietin (rhEPO) on the responses of growth hormone (GH), prolactin (PRL) and thyrotropin (TSH) to thyrotropin-releasing hormone (TRH) stimulation in acromegalic patients. Methods: We studied 16 patients (8 females, aged 29±68 years) with active acromegaly and 12 control subjects (7 females, 24±65 years). All participants were tested with TRH (400 mg i.v. as bolus) and with TRH plus rhEPO (40 U/kg at a constant infusion rate for 30 min, starting 15 min before TRH injection) on different days. Blood samples were obtained between À30 and 120 min for GH and PRL determinations, and between À30 and 90 min for TSH determinations. Hormone responses were studied by a time-averaged (area under the secretory curve (AUC)) and time-independent (peak values) analysis. Results: Twelve patients exhibited a paradoxical GH reaction after TRH administration with great interindividual variability in GH levels. When patients were stimulated with rhEPO plus TRH there were no changes in the variability of GH responses or in the peak and AUC for GH secretion. Infusion with rhEPO did not induce any signi®cant change in GH secretion in normal subjects. Baseline and TRH-stimulated PRL concentrations in patients did not differ from those values found in controls. When TRH was injected during the rhEPO infusion, a signi®cant (P < 0.05) increase in PRL concentrations at 15±120 min was found in acromegalic patients. Accordingly, the PRL peak and the AUC for PRL secretion were signi®cantly increased in patients. Infusion with rhEPO had no effect on TRH-induced PRL release in control subjects. Baseline TSH concentrations, as well as the TSH peak and the AUC after TRH, were signi®cantly lower in patients than in controls. Infusion with rhEPO modi®ed neither the peak TSH reached nor the AUC for TSH secretion after TRH injection in acromegalic patients and in healthy volunteers. Conclusion: Results in patients with acromegaly suggest that (i) the paradoxical GH response to TRH is not modi®ed by rhEPO infusion, (ii) rhEPO has no effect on TRH-induced TSH release, and (iii) acute rhEPO administration increases the TRH-induced PRL release in acromegalic patients.

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Section: Discussionsupporting

confidence: 57%

Section: Growth Hormone Responsesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of acute infusion of erythropoietin on paradoxical responses of growth hormone to thyrotropin-releasing hormone in acromegalic patients

Iglesias²,

Sastre³

et al. 2000

European Journal of Endocrinology

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“…As TRH, LH-RH, somatostatin and dopamine modulate the GH secretion from acromegalic pituitary either in vivo or in vitro, the presence of respective receptors has been postulated (Irie and Liuzzi et al (1974) have already reported the mutual relationships between the responses to TRH and to dopaminergic agents in these patients. In the present study, the responses to hpGHRF-44 and those to several other agents were compared ; i.e.…”

mentioning

confidence: 99%

Comparative study on the responses of plasma GH to synthetic GH-releasing factor and other stimulatory and inhibitory agents in patients with acromegaly.

Hanew

Sato

Sasaki

et al. 1985

Tohoku J. Exp. Med.

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Ten patients with active acromegaly received synthetic human pancreatic GH releasing factor (hpGHRF-44), and the GH responses to GHRF were compared with the basal GH levels and with the GH responses to arginine, TRH, LH-RH, somatostatin, and L-dopa. There were no significant relationships between the plasma GH responses to GHRF and the results of the stimulatory and inhibitory tests mentioned above, except that the responses to GHRF showed weak positive or negative correlations with the responses to LH-RH (r= +0.56) or with the basal GH levels (r--0.57). These results indicate that acromegalic somatotrophs would have GHRF receptors as well as several other receptors to hypothalamic hormones and to dopamine, and that there might be no distinct relationship between the somatotroph sensitivities to GHRF and to other stimulatory or inhibitory stimuli. Further studies are required regarding the weak correlations between the response to GHRF and that to LH-RH or basal GH value.

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“…acromegaly ; GH ; sulpiride ; domperidone ; dopamine ; TRH It is well known that acromegalic patients are apt to show paradoxical growth hormone (GH) decreases to exogenously administered dopamine (DA) and dopaminergic agonists Liuzzi et al 1974;Oppizi et al 1980). Similar GH decreases to these agents are also observed in GH-secreting adenomas in vitro (Mashiter et al 1977;Peillon et al 1979).…”

mentioning

confidence: 99%

Plasma growth hormone responses to sulpiride in patients with acromegaly.

Hanew

Sato

Sasaki

et al. 1984

Tohoku J. Exp. Med.

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The role of endogenous dopamine (DA) on plasma GH secretion was studied in 12 patients with active acromegaly.After intramuscular administration of 100 mg sulpiride, 3 out of 12 patients showed distinct increases in their plasma GH (cases 1-3:sulpirideresponders).The GH increases far exceeded the ranges of physiological fluctuation in two cases studied (case 1 & 3). After domperidone administration, case 3 showed a quite similar GH increase as after sulpiride.Plasma GH responses to TRH and sulpiride were still observed in case 2 even after the basal GH levels were normalized by the transsphenoidal hypophysectomy.The three sulpiride-responders showed so-called paradoxical GH decreases following the administration of L-dopa (500 mg, p.o.) or DA (5pg/kg/min over 90 min, i.v.). However, the basal plasma PRL levels and the responses to sulpiride in these 3 cases were not homogeneous.These results indicate that endogenous DA has a tonic inhibitory effect on GH secretion in some cases of acromegaly, and that tumorous somatotrophs rather than elevated GH levels are the critical factor for such inhibition. Further, the sensitivities of somatotrophs and lactotrophs to DA appeared to be heterogeneous in acromegalic patients.acromegaly ; GH ; sulpiride ; domperidone ; dopamine ; TRH It is well known that acromegalic patients are apt to show paradoxical growth hormone (GH) decreases to exogenously administered dopamine (DA) and dopaminergic agonists Liuzzi et al. 1974; Oppizi et al. 1980). Similar GH decreases to these agents are also observed in GH-secreting adenomas in vitro (Mashiter et al. 1977;Peillon et al. 1979). These findings suggest a role of DA in the secretion of GH in acromegalic patients. Effects produced by pharmacological doses of DA-agonists, however, do not necessarily imply that endogenous DA has a direct suppressive effect on the somatotrophs.To test whether this is in fact the case, we examined the effect of DA-

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Growth Hormone (GH)-Releasing Activity of TRH and GH-Lowering Effect of Dopaminergic Drugs in Acromegaly: Homogeneity in the Two Responses

Cited by 126 publications

References 0 publications

Effects of acute infusion of erythropoietin on paradoxical responses of growth hormone to thyrotropin-releasing hormone in acromegalic patients

Effects of acute infusion of erythropoietin on paradoxical responses of growth hormone to thyrotropin-releasing hormone in acromegalic patients

Comparative study on the responses of plasma GH to synthetic GH-releasing factor and other stimulatory and inhibitory agents in patients with acromegaly.

Plasma growth hormone responses to sulpiride in patients with acromegaly.

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