Clonidine pretreatment modifies the growth hormone secretory pattern induced by shortterm continuous GRF infusion in normal man

Lima, Luís; Arce, V.; Díaz, María Jesús Villamide; Tresguerres, Jesús A.F.; Devesa, Jesús

doi:10.1111/j.1365-2265.1991.tb03510.x

Cited by 14 publications

(7 citation statements)

References 35 publications

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“…The data obtained in this study agree with previous findings of our group, demonstrating that the administra tion of CLO cojointly with GRF results in a synergistic stimulation of GH release in humans [8][9][10], dogs [11], and rats [13,14], Lanzi et al [15] recently confirmed our 555 results in rats. The potentiating effect of CLO on the GH response to GRF is more clearly seen when the somatostatinergic input to the pituitary is physiologically [8.…”

Section: Discussionsupporting

confidence: 83%

“…Initial data in rats suggested that this effect was dependent on the stimulation by CLO of hypothalamic GH-releasing hormone (GH-RH) release [3][4][5][6][7], Yet a wealth of other evidence indicated that in GH control. CLO might act mainly by inhibiting the hypotha- lamic secretion of somatostatin (SS), at least in humans [8][9][10], dogs [II], and rabbits [ 12]. Hence it appeared that, depending on the species, different mechanisms might be responsible for the GH-releasing effect of ctyadrenoceptor agonism.…”

Section: Introductionmentioning

confidence: 99%

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Clonidine Potentiates the Growth Hormone Response to a Growth Hormone Releasing Hormone Challenge in Hypothalamic Growth Hormone Releasing Hormone Deficient Rats

Arce

Barros

Vara³

et al. 1995

Neuroendocrinology

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This study was designed to further investigate our postulate regarding the inhibitory role played by central α ₂-adrenergic pathways on hypothalamic somatostatin (SS) release in rats. The growth hormone (GH) responses to exogenous GH-releasing factor (GRF; 3 µg/kg i.v.) or clonidine (CLO; 100 µg/kg i.v.), either given alone or in combination, were tested in 3-month-old male rats made GH-releasing hormone (GH-RH) deficient neonatally by administration of monosodium glutamate (MSG; 4 mg/g body weight s.c). To prevent the presumable decrease in the pituitary GH content in these animals from leading to an erroneous interpretation of the results obtained, half of these rats were given GRF (MSG-GRF rats; 30 µg/kg s.c.) for 3 days immediately prior to GH testing. The other half of MSG-treated and non MSG-treated rats received saline during these days (MSG-S and controls, respectively). To establish the efficiency of GRF priming, the pituitary GH content was measured in other MSG-GRF, MSG-S, and control animals. The mean (±SEM) GH peaks in response to GRF challenge were significantly higher in controls than in MSG-GRF rats (125.2 ± 28.5 vs. 67.5 ± 19.4 µg/l; p < 0.05), while no significant GRF-induced GH release was observed in the MSG-S group. Most likely these results are related to the different pituitary GH content, significantly (p < 0.01) higher in controls than in MSG-GRF rats, and in the latter higher than in MSG-S animals (p < 0.05). CLO administration did not evoke a significant GH release in MSG rats, whether primed with GRF or not. The maximal GH peak in response to the α₂-adrenergic agonist (25 ± 3.2 µg/l) in controls was significantly lower (p < 0.01) than that elicited by GRF. Pretreatment with CLO significantly (p < 0.01) enhanced the GH response to GRF in control (640.6 ± 57.9 µg/l) and in MSG-GRF rats (324.3 ± 76.4 µg/l), but it produced no effect in MSG-S animals. These results indicate that α ₂-adrenergic agonism is able to potentiate the GH response to GRF in GH-RH-deficient rats. Since we have reported a similar synergistic effect in rats exhibiting pharmacologically increased SS release, it can be concluded that, in this species, CLO acts by inhibiting the hypothalamic release of SS rather than by stimulating endogenous GH-RH release.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Clonidine Potentiates the Growth Hormone Response to a Growth Hormone Releasing Hormone Challenge in Hypothalamic Growth Hormone Releasing Hormone Deficient Rats

Arce

Barros

Vara³

et al. 1995

Neuroendocrinology

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“…30 for review], and although evidence obtained in experiments with rats suggests for CLO an action mediated via GHRH release [19][20][21][22], the possibility has to be considered that it may also act via inhibition of somatostatin release [II, 23,24], In this vein, recent studies have shown that CLO increases the GH release to GHRH both in obese children [31] and in normal men [32], This effect appears to be dependent on a decreased somatostatinergic input to the pituitary, re sulting as a consequence of a 2-adrenergic agonism. In the present study we did not measure the effect on GH re lease of CLO alone; however, it seems unlikely that the 4-fold increase in the GH response to GHRH following CLO was due to the drug-induced stimulation of endo genous GHRH release.…”

Section: Discussionmentioning

confidence: 99%

Combined Administration of Growth-Hormone-Releasing Hormone and Clonidine Restores Defective Growth Hormone Secretion in Old Dogs

et al. 1993

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We have studied in old dogs the effects of short-term administration of growth hormone (GH)-releasing hormone (GHRH) alone or co-administered with clonidine (CLO), an ct2-adrenergic agonist, on the GH secretory pattern (cluster analysis), and GH responsiveness to an acute GHRH or GHRH + CLO challenge and plasma somatomedin C (SMC) levels. Dogs were given either GHRH alone twice daily for 10 days (treatment 1) or combined GHRH + CLO both given twice daily (treatment 2) or GHRH + CLO given once daily (treatment 3). Animals were sampled from 09.00 to 15.00 h, at 10-min intervals, both before and 14 h after treatments. At the end of the 6-hour sampling period, dogs were challenged with simultaneous administration of GHRH and CLO, while they were tested with GHRH alone on the morning of the following day. In dogs undergoing treatment 1, acute administration of GHRH or GHRH + CLO elicited mean GH peak responses higher than before treatment, but none of the GH secretory indices were modified during the 6-hour sampling period, except for the increase in mean GH peak amplitude. In dogs undergoing treatment 2, acute administration of GHRH elicited a mean GH peak response higher than that before treatment, whereas administration of GHRH + CLO induced a mean GH peak response not different from that elicited by GHRH + CLO before treatment or by GHRH alone after treatment. However, this treatment significantly augmented the frequency of spontaneous bursts of GH secretion, the mean GH peak amplitude and the total peak area. In dogs undergoing treatment 3, acute administration of GHRH alone or GHRH + CLO elicited a mean GH peak response higher than that elicited by the same drugs before treatment. Moreover, there was an increase of GH peak frequency, mean GH peak amplitude and total peak area, even higher than after treatment 2. Plasma SMC levels rose significantly after all treatments, treatment 3 being the most effective in this instance. These data demonstrate that: (1) both a hypothalamic and a pituitary component play a role in the defective GH secretion in old dogs; (2) GH hypofunction is not an irreversible event, since GH secretion may be restored by pharmacological means acting at both the pituitary and the hypothalamic level, and (3) CLO given only once daily was more effective than CLO given twice daily, perhaps due to the property of this drug to down-regulate at high doses hypothalamic α₂-adrenoceptors.

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“…In addition, many recent data indicate that the aging-suppressor gene Klotho is a direct regulator of GH secretion [35]. However, we still think that the CLO+GHRH test is a clear reproducible and safe test for analyzing possible states of GH-deficiency and its causes, even in adulthood [36].…”

Section: Discussionmentioning

confidence: 99%

Clonidine Plus GHRH Administration for Diagnosing Growth Hormone Deficiency in Children

Devesa¹

2017

J Clin Mol Endocrinol

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Objective: To analyze the effectiveness and reproductivity of a challenge with clonidine (CLO) plus GHRH administration to establish a state of GH-deficiency and the causes of it.Methods: 24 children (17M, 7F) with stature <1 or 2 SD from P3, previously studied with different classical tests, were given CLO (150 µg/m2 orally, at time 0') plus GHRH (60' later, 1 µg/kg, iv). This test was repeated but giving placebo at time 0'. For comparison purposes, 20 agematched normal children (14M, 6F) were studied. Growth velocity (GV) and bone age (BA) before performing CLO +GHRH were considered.Results: While classical GH tests show a great variability of negative or positive GH responses in the same short patient, all but two patients significantly responded to CLO+GHRH (GH peak: 42.2 ± 19 vs. 41.6 ± 3.5 in controls). Controls showed a significant positive correlation between the amplitude of GH response and chronological and bone age (R=0.832; F=37.6; P=0.001, multiple regression analysis): y=a+b × BA+c × CA, where y=GH peak, BA=bone age, CA=chronological age, and a, b and c are constants. This equation allows to establish the value of GH peak theoretically obtained after CLO+GHRH challenge in a normal child. Applying this equation to the responses to CLO+GHRH in short children a deviation, ranging between -435% and +41%, was obtained between theoretical and real GH peaks (%DT-R). Responses between -20% to +20% were considered normal. Plotting these responses (% DT-R) against the SD of the mean of the BA to GV ratio in normal children, five populations were defined: 1) Low response and low GV for BA; 2) Low response and normal GV for BA; 3) Normal response and low GV for BA; 4) Normal response and normal GV for BA; and 5) High response and low GV for BA. Conclusion:The test CLO+GHRH is safe, effective and unique to detect GH-deficiency and its causes in short children and adults.

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Clonidine pretreatment modifies the growth hormone secretory pattern induced by shortterm continuous GRF infusion in normal man

Cited by 14 publications

References 35 publications

Clonidine Potentiates the Growth Hormone Response to a Growth Hormone Releasing Hormone Challenge in Hypothalamic Growth Hormone Releasing Hormone Deficient Rats

Clonidine Potentiates the Growth Hormone Response to a Growth Hormone Releasing Hormone Challenge in Hypothalamic Growth Hormone Releasing Hormone Deficient Rats

Combined Administration of Growth-Hormone-Releasing Hormone and Clonidine Restores Defective Growth Hormone Secretion in Old Dogs

Clonidine Plus GHRH Administration for Diagnosing Growth Hormone Deficiency in Children

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