Pyridostigmine-mediated growth hormone release: evidence for somatostatin involvement.

Wehrenberg, William B.; Wiviott, Stephen D.; Voltz, Donald M.; Giustina, Andrea

doi:10.1210/endo.130.3.1347008

Cited by 26 publications

(23 citation statements)

References 27 publications

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“…The increase in plasma GH concentrations would enhance hypothalamic SS tone (and probably reduce concomitantly the activity of GHRH-secreting neurons) (43±47), thus blunting the subsequent responsiveness to GHRH. Supporting this proposition is the ®nding that a cholinergic drug, pyridostigmine, which inhibits SS release (48), given before the second GHRH bolus, reinstates GH responsiveness to the peptide in humans (49,50).…”

Section: Discussionmentioning

confidence: 94%

Growth hormone (GH) rebound rise following somatostatin infusion withdrawal: studies in dogs with the use of GH-releasing hormone and a GH-releasing peptide

Rigamonti

Cavallera

Bonomo³

et al. 2001

European Journal of Endocrinology

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Objective: Evidence has been presented that in both animals and humans the rebound secretion of growth hormone (GH) following withdrawal of an infusion of somatostatin (SS) is due to the functional activation of the hypothalamic GH-releasing hormone (GHRH) neurons of the recipient organism. Based on this premise, this study has sought to assess the existence of functional interactions between endogenous GHRH released by a SS infusion withdrawal (SSIW) and growth hormone-releasing peptides (GHRPs), a class of compounds allegedly acting via GHRH. Methods: Five young dogs (3 to 4 years old, 2 male and 3 female) were administered, on different occasions, three consecutive intravenous boli of physiological saline (0.1 ml/kg), or GHRH (2 mg/kg), or EP92632 (125 mg/kg), a GHRP compound, or GHRH plus EP92632 at the end of three cycles of 1-h SS infusions (8 mg/(kgÂh)) or during a 6-h infusion of saline. Results: Under saline infusion (SALI), plasma GH levels were unaltered, whereas each SSIW cycle was followed by similar GH secretory episodes. Administration of the ®rst GHRH bolus under SALI induced a rise in plasma GH concentrations slightly higher than that induced by the ®rst cycle of SSIW, but the GH response to the second and third GHRH boli was similar to that after SSIW. Following SSIW, the response to the ®rst bolus of GHRH was higher than that during SALI, but the second and third cycles of SSIW induced GH responses similar to those evoked by the GHRH bolus. During SALI, administration of the ®rst bolus of EP92632 induced a rise in plasma GH which was higher than that induced by the ®rst GHRH bolus, the second bolus elicited a GH peak of lesser amplitude and there was a partial restoration of the GH response to the third peptide bolus. SSIW strikingly enhanced the GH release to the ®rst EP92632 bolus, a pattern also present, although to a lesser extent, with the second and third cycles of SSIW. Under SALI, combined administration of GHRH and EP92632 had a synergistic effect on GH release, but a progressive reduction was present in the GH response to the second and third GHRH plus EP92632 boli. SSIW increased only weakly the GH response to the ®rst co-administration of the peptides over that present after administration of EP92632 alone, and did not induce a GH response higher than that present during SALI when the second bolus of the peptides was administered; after the third SSIW a GH rise higher than that present during SALI was elicited by the combined administration of the peptides. Conclusions: (i) the uniformity of the GH rebound responses to multiple cycles of SSIW may indicate that the latter activate a physiological mechanism which mimics that normally controlling GH pulse generation; (ii) EP92632 elicits, under our experimental conditions, a plasma GH rise higher than that induced by GHRH; (iii) SSIW enhances the GH response to EP92639 alone, to an extent reminiscent of that following combined administration of GHRH and EP92632. This pattern reinforces the view that SSIW elicits release of end...

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Section: Discussionmentioning

confidence: 94%

Growth hormone (GH) rebound rise following somatostatin infusion withdrawal: studies in dogs with the use of GH-releasing hormone and a GH-releasing peptide

Rigamonti

Cavallera

Bonomo³

et al. 2001

European Journal of Endocrinology

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“…Although we did not include the test that demonstrates that PST pretreatment does not increase the TSH response to TRH, we previously had demonstrated that 120mg of PST could not affect TRH-stimulated TSH response (33). Therefore, the comparable TSH responses between Test 2 and 5 exclude the possibility that glucose ingestion suppresses the TRH-induced TSH response after pretreatment with PST.The activation of the cholinergic system inhibits the release of SRIH from the rat hypothalamus in vitro (20) and in vivo (14,28,30) and thereby increases GH secretion. PST, a cholinesterase inhibitor, is known to increase both basal (9,15) and GHRH-induced GH release in man (2,6,8,10,13,19,21).…”

mentioning

confidence: 99%

Suppression of TRH-Stimulated TSH Secretion by Glucose-Induced Hypothalamic Somatostatin Release

Yang

Woo²,

Kim³

et al. 1996

Horm Metab Res

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To determine whether the combined glucose-thyrotropin-releasing hormone (TRH) test can be a useful method for the evaluation of the hypothalamic somatostatinergic activity, we investigated whether TRH-induced thyroid stimulating hormone (TSH) secretion can be suppressed by the oral glucose administration that stimulates the hypothalamic somatostatin (SRIH) secretion. Six tests were performed in ten healthy young men. Test 1: 1 ml of normal saline was intravenously administered at 0 min. Test 2: TRH was administered intravenously at 0 min. Test 3: Glucose, 75 g, was administered orally at -60 min. Test 4: Glucose and TRH were administered as above. Test 5: Pyridostigmine (PST), 120 mg, was given orally at -90 min followed by the administration of GH and TRH as above. Basal TSH levels were suppressed slightly, but significantly. In Test 3 compared to those observed in Test 1. The oral glucose administration also significantly suppressed TRH-stimulated TSH response by 27-35% between 40 min and 80 min in Test 4. In contrast, the pretreatment with PST completely reverted the suppressive effect of glucose on TRH-stimulated TSH response in Test 5. These data suggest that the increased hypothalamic SRIH secretion induced by oral glucose administration can suppress TRH-stimulated TSH response in normal men, and the combined glucose-TRH test can be a useful method to evaluate the hypothalamic somatostatinergic activity.

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“…5), the GH response to GHRH after saline infusion appeared to be exaggerated in comparison to the response range usually observed in normal subjects. This observation suggests the existence of two subgroups of acromegalics: one with normal and the other with exaggerated [27] GH response to GHRH. Interestingly, also in the patient with GH hyperresponsiveness to GHRH hydrocortisone inhibited the GH response to GHRH, suggesting similar sensitivity to acute hypercortisolism, and therefore somatostatin in crease, in the two subgroups of acromegalic patients.…”

Section: Discussionmentioning

confidence: 88%

Effect of Hydrocortisone on the Growth Hormone Response to Growth Hormone-Releasing Hormone in Acromegaly

Giustina

Bussi²,

Doga

et al. 1994

Horm Res

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Our recent data show that acute and sustained hypercortisolism decreases circulating growth hormone (GH) levels in acromegaly with respect to saline infusion. It has been hypothesized that in acromegalic patients, as well as in normal subjects, short-term increases in serum cortisol levels may be able to cause an enhancement of hypothalamic somatostatin secretion, which in turn may be responsible for the glucocorticoid mediated GH inhibition. The aim of our study was to investigate the acute effects of an intravenous infusion of hydrocortisone on the GH response to growth hormone-releasing hormone (GHRH) in acromegaly. We studied 6 adult patients with active acromegaly (3 M, 3 F; mean age 60.5 ± 4.1 years; mean body mass index 27.1 ± 0.6 kg/ m²). All the patients underwent: (1) a bolus intravenous injection of 100 mg hydrocortisone succinate in 2 ml saline, at time -60 followed by a 120-min intravenous infusion of 250 mg hydrocortisone succinate in 250 ml saline, from -60 to 60 min; (2) a bolus intravenous injection of human GHRH 1-29NH₂ 100 µg in 1 ml saline, 60 min after initiation of a 2-hour hydrocortisone infusion; (3) a bolus intravenous GHRH injection 60 min after initiation of a 2-hour saline infusion. In all of the acromegalic patients during hydrocortisone succinate infusion, GH values clearly decreased with respect to basal levels (mean nadir 47 ± 8.6%, p < 0.05 with respect to basal levels). After GHRH injection and saline infusion all the patients showed a significant increase in GH levels (mean peak 231.5 ± 52.8%, p < 0.05). After hydrocortisone + GHRH administration, all 6 patients showed absolute GH values not significantly different with respect to hydrocortisone alone and GH peaks after GHRH were significantly lower with respect to saline + GHRH (mean GH peak levels 118.8 ± 12.9 vs. 231.5 ± 52.8%, p < 0.05). We conclude that acute administration of pharmacological doses of glucocorticoids is able to decrease the GH response to GHRH in patients with acromegaly probably through an enhancement of endogenous somatostatin tone.

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Pyridostigmine-mediated growth hormone release: evidence for somatostatin involvement.

Cited by 26 publications

References 27 publications

Growth hormone (GH) rebound rise following somatostatin infusion withdrawal: studies in dogs with the use of GH-releasing hormone and a GH-releasing peptide

Growth hormone (GH) rebound rise following somatostatin infusion withdrawal: studies in dogs with the use of GH-releasing hormone and a GH-releasing peptide

Suppression of TRH-Stimulated TSH Secretion by Glucose-Induced Hypothalamic Somatostatin Release

Effect of Hydrocortisone on the Growth Hormone Response to Growth Hormone-Releasing Hormone in Acromegaly

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