Blockade of cholinergic muscarinic receptors by pirenzepine and GHRH-induced GH secretion in the acute and recovery phase of anorexia nervosa and atypical eating disorders

Rolla, M; Andreoni, A.; Belliti, D.; Cristofani, R.; Ferdeghini, M; Müller, Eugenio E.

doi:10.1016/0006-3223(91)90250-p

Cited by 33 publications

(20 citation statements)

References 27 publications

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“…The existence of a robust somatotroph responsiveness to GHRH in A-AN is widely acknowledged (5,7,8,26), although few exceptions have also been reported (45). In the present study, the GHRH-induced GH response in A-AN overrode the one recorded in NW, whereas it was within normal limits in R-AN.…”

Section: Discussioncontrasting

confidence: 51%

“…Indeed, the analysis of GH pulsatility in AN has documented an increased frequency of GH secretory pulses (6), which might be due to increased frequency of GHRH discharges (50). In R-AN the GH response after SSIW was nearly superimposable on that observed in NW, which would denote subsiding of GHRH hyperfunction in this phase of the disease (8).…”

Section: Discussionmentioning

confidence: 99%

“…The view of a reduced hypothalamic somatostatinergic tone in AN rests on the presence of elevated interpulse GH levels (50) and of low CSF concentration of SS (29), as well as on the finding that substances acting via stimulation of hypothalamic SS release, while capable of abolishing the GH response to GHRH in normal subjects (28), only blunt it in anorectic patients (7,8). Conversely, substances that inhibit hypothalamic SS release, such as pyridostigmine, an indirect cholinergic agonist, or atenolol, a b1-adrenergic antagonist, while capable of potentiating the GH response to GHRH in normal subjects (28), fail to do so in AN (25,26).…”

Section: Time (Min)mentioning

confidence: 99%

“…In fact, so far, low or absent GH response to insulin-induced hypoglycemia (17) or dopaminergic agonists (18), exaggerated GH responses to GHRH (7,8,19,20), paradoxical GH rises after glucose load (21,22), thyrotropin-releasing hormone (23), or gonadotropin-releasing hormone (GnRH) (24) have been reported. GH secretion in AN has also been shown to be particularly refractory to the inhibitory effect of muscarinic cholinergic antagonists (7,8), as well as to the stimulatory effect of cholinergic agonists or b-adrenergic antagonists (25,26), or acute glucorticoid administration (27). As central cholinergic and b-adrenergic functions and glucorticoids would influence GH secretion via modulation of hypothalamic SS release (28), the existence of an impaired SS activity in AN has also been suggested (5,6,8,25,26).…”

Section: Introductionmentioning

confidence: 99%

“…GH secretion in AN has also been shown to be particularly refractory to the inhibitory effect of muscarinic cholinergic antagonists (7,8), as well as to the stimulatory effect of cholinergic agonists or b-adrenergic antagonists (25,26), or acute glucorticoid administration (27). As central cholinergic and b-adrenergic functions and glucorticoids would influence GH secretion via modulation of hypothalamic SS release (28), the existence of an impaired SS activity in AN has also been suggested (5,6,8,25,26). Along this line also are the low cerebrospinal fluid (CSF) concentrations of SS detected in anorectic patients (29).…”

Section: Introductionmentioning

confidence: 99%

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Somatostatin infusion withdrawal: studies in the acute and recovery phase of anorexia nervosa, and in obesity

Pincelli¹,

Rigamonti²,

Scacchi³

et al. 2003

European Journal of Endocrinology

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Objective: Changes in GH/IGF-I axis activity occur in both anorexia nervosa (AN) and obesity (OB). A GH hypersecretory state with very low plasma IGF-I levels is present in AN, whereas in morbid OB, GH secretion is dull and plasma IGF-I levels are generally preserved. Endogenous GHRH activity in AN and OB has never been directly studied, although indirect evidence would indicate that GHRH function is altered in either condition, possibly enhanced and reduced respectively. Somatostatin (SS) infusion withdrawal (SSIW) is followed by a rebound rise of plasma GH in animals and humans, an event which, allegedly, is mediated by endogenous GHRH release. Methods: In the present study, 28 young women, eight with active AN (A-AN), six with AN in the recovery phase (R-AN), eight with morbid OB, and six healthy age-matched normal weight subjects (NW), were studied. All subjects underwent, on different occasions, the following two tests: (i) acute GHRH injection (1 mg/kg, i.v.); (ii) infusion of SS (9 mg/kg per h i.v. over 60 min), with blood samples drawn prior to and at different intervals after drug injections. Plasma GH levels were measured at each time interval in all sessions, and, in addition, baseline plasma estradiol, free triiodothyronine, TSH, IGF-I and insulin were measured at 2 30 min. Results: Baseline plasma GH concentrations were significantly higher in A-AN than in NW ð4:7^0:7 vs 2:1^0:6 mg=l; P , 0:01Þ: Baseline GH levels in R-AN were also higher than in NW, but the difference did not reach statistical significance (5:6^1:7 mg=l; not significant (NS)). Baseline plasma GH concentrations were significantly lower in OB than in NW ð0:3^0:1 mg=l; P , 0:01Þ: GHRH-stimulated GH release was significantly higher in A-AN than in NW (mean change in area under the curve (DAUC) 1904:9^626:1 vs 613:9^75:9 mg=l per min, P , 0:01), whereas no statistically significant difference was present between R-AN and NW (mean DAUC 638:2^293:0 mg=l per min, NS); in OB, GHRH failed to evoke a plasma GH rise (mean DAUC 239:8^89:9 mg=l per min vs A-AN, R-AN, and NW, P , 0:01). SS infusion markedly reduced plasma GH concentrations in both A-AN and R-AN and, to a lesser extent, in NW, but failed to do so in OB. In A-AN, SSIW was followed by a plasma GH rise markedly higher than that present in NW (mean DAUC 193:0^42:3 vs 60:1^11:4 mg=l per min, P , 0:01), whereas in R-AN the GH response after SSIW was nearly superimposable on that registered in NW (mean DAUC 72:9^22:8 mg=l per min, NS). There were no changes in plasma GH levels after SSIW in OB (mean DAUC 22:8^9:7 mg=l per min). In all groups, DAUCs of the GH response to GHRH and after SSIW were highly positively correlated ðr ¼ 0:7; P , 0:01Þ: Conclusions: These data support the view that a high endogenous GHRH tone, which subsides in the recovery phase of the disease, is present in AN, whereas GHRH hypofunction, possibly associated with pituitary impairment, might indicate OB.

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