Pituitary response to auditory stress: effect of treatment with α-methyl-p-tyrosine. Usefulness of a factorial mixed design for statistical analysis

1976 ◽  
Vol 54 (4) ◽  
pp. 596-602 ◽  
Author(s):  
R. Collu ◽  
J.-C. Jéquier
Keyword(s):  
Inhibitory Effect ◽  
Plasma Corticosterone ◽  
Repeated Measurements ◽  
Male Rats ◽  
Stress Effect ◽  
Intraventricular Administration ◽  
Mixed Design ◽  
Gh Secretion ◽  
Plasma Gh ◽  
Auditory Stress

Eight adult male rats were chronically cannulated in the jugular vein and placed individually in a sound-attenuated cubicle. Four of the animals were also implanted with a permanent cannula in the right lateral ventricle of the brain. Each animal was submitted twice to auditory stress at a 24-h interval. Before each stress, the rats were pretreated with either saline or α-methyl-p-tyrosine (α-MT), the order of administration of the drug and its vehicle being alternated in the eight rats. The injections were made either intravenously or intraventricularly. Auditory stress significantly depressed plasma growth hormone (GH) levels irrespective of the type of pretreatment. Mean plasma GH levels were significantly lower after α-MT pretreatment. α-MT pretreated animals had higher mean plasma corticosterone (B) levels which remained unchanged during stress. Plasma follicle stimulating hormone (FSH) levels were not modified by stress nor by α-MT pretreatment. The intraventricular administration of α-MT at a dose (20 mg/kg) which is ineffective by a systemic route produced the same effects on GH and B levels as the intravenous injection (250 mg/kg). These data seem to indicate that auditory stress exerts its inhibitory effect on GH secretion through a noncatecholaminergic pathway. They show, on the other hand, the existence of a central catecholaminergic tonus, stimulatory for GH and inhibitory for B.Statistical analysis was based on a factorial mixed design for repeated measurements after logarithmic transformation of the data. The purpose, advantages and limits of this procedure are presented and discussed.

Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat

1996 ◽  
Vol 135 (4) ◽  
pp. 481-488 ◽  
Author(s):  
Antonio Torsello ◽  
Roberta Grilli ◽  
Marina Luoni ◽  
Margherita Guidi ◽  
Maria Cristina Ghigo ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Mechanism Of Action ◽  
Direct Action ◽  
Male Rats ◽  
Surgical Ablation ◽  
Adult Rats ◽  
Gh Secretion ◽  
Plasma Gh

Torsello A, Grilli R, Luoni M, Guidi M, Ghigo MC, Wehrenberg WB, Deghenghi R, Müller EE, Locatelli V. Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat. Eur J Endocrinol 1996;135:481–8. ISSN 0804–4643 We have reported Hexarelin (HEXA), an analog of growth hormone-releasing peptide 6 (GHRP-6), potently stimulates growth hormone (GH) secretion in infant and adult rats. This study was undertaken to further investigate Hexarelin's mechanisms of action. In 10-day-old pups, treatments with HEXA (80 μg/kg, b.i.d.) for 3–10 days significantly enhanced, in a time-related fashion, the GH response to an acute HEXA challenge. Qualitatively similar effects were elicited in pups passively immunized against growth hormone-releasing hormone (GHRH) from birth. In adult male rats, a 5-day pretreatment with HEXA (150 μg/kg, b.i.d.) did not enhance the effect of the acute challenge, and the same pattern was present after a 5-day pretreatment in male rats with surgical ablation of the mediobasal hypothalamus (MBH-ablated rats). In addition, in adult sham-operated rats, Hexarelin (300 μg/kg, iv) induced a GH response greater (p < 0.05) than that induced by GHRH (2 μg/kg, iv). However, in MBH-ablated rats 7 days after surgery, GHRH was significantly (p < 0.05) more effective than HEXA, and 30 days after surgery HEXA and GHRH evoked similar rises of plasma GH. Finally, the in vitro Hexarelin (10−6 mol/l) effect was transient while GHRH (10−8 mol/l) induced a longer lasting and greater GH release. Three different mechanisms, not mutually exclusive, are postulated for Hexarelin stimulation of GH secretion in vivo: a direct action on the pituitary, though of minor relevance; an indirect action that involves release of GHRH, of relevance only in adult rats; and an action through the release of a still unknown hypothalamic "factor", which in infant and adult rats elicits GH release acting sinergistically with GHRH. Antonio Torsello, Department of Pharmacology, via Vanvitelli 32, 20129 Milano, Italy

Growth hormone secretion in stalk-sectioned rats

1991 ◽  
Vol 124 (6) ◽  
pp. 700-706 ◽  
Author(s):  
Jun Kamegai ◽  
Ichiji Wakabayashi ◽  
Hitoshi Sugihara ◽  
Shiro Minami ◽  
Taiko Kitamura ◽  
...  
Keyword(s):  
Adrenal Glands ◽  
Gh Deficiency ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Male Rats ◽  
Gh Secretion ◽  
The Face ◽  
Prolactin Response ◽  
Plasma Gh ◽  
Trough Levels

Abstract. Idiopathic pituitary GH deficiency appears to result from neonatal disruption of hypophyseal portal vessels in the majority of patients. To examine the mechanism of GH deficiency associated with the disease, the effect of pituitary stalk section on GH secretion was studied in rats. Adult male rats were subjected to stalk section without inserting an impermeable membrane between the cut ends. They were studied 3 to 4 weeks after surgery. In stalk-sectioned rats, pituitary weight, body weight and hypothalamic SRIH content were significantly reduced as compared with sham-operated rats. Hypothalamic GHRH content, plasma T3, T4, corticosterone and testosterone levels, and weights of testes remove and adrenal glands were comparable in the two groups. Plasma GH profiles of sham-operated rats showed characteristic periodic pulses occurring at 2.5-3 h intervals with intervening trough period. In stalk-sectioned rats, plasma GH levels were low with small fluctuations, but GH levels were significantly higher than trough levels of sham-operated rats. The amount of GH secreted during a 6-h period as measured by planimetry was significantly reduced. To ascertain the regeneration of hypophyseal portal vessels, post SRIH rebound in GH secretion, which requires the presence of endogenous GHRH, was examined. Withdrawal of exogenous SRIH infusion triggered a large rebound GH secretion whose magnitude did not differ between groups. In stalk-sectioned rats, GH response to met-enkephalin analogue, FK 33-824, was not observed, whereas prolactin response to the secretagogue was observed in the majority of rats. It appears that in stalksectioned rats, hypophyseal portal circulation is re-established, but GHRH release from the hypothalamus is impaired in the face of sufficient supply of other hypophysiotropic hormones.

Somatostatin tonically inhibits growth hormone secretion in domestic fowl

1986 ◽  
Vol 111 (1) ◽  
pp. 91-97 ◽  
Author(s):  
S. Harvey ◽  
S.-K. Lam ◽  
T. R. Hall
Keyword(s):  
Growth Hormone ◽  
Domestic Fowl ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Passive Immunization ◽  
Inhibitory Effect ◽  
Gh Secretion ◽  
Basal Plasma ◽  
Plasma Gh

ABSTRACT Passive immunization of immature chickens with sheep somatostatin (SRIF) antiserum promptly increased the basal plasma GH concentration and augmented TRH-induced GH secretion. Although exogenous SRIF had no inhibitory effect on the basal GH concentration in untreated birds or birds pretreated with non-immune sheep serum, it suppressed the stimulatory effect of SRIF immunoneutralization on GH secretion. These results suggest that SRIF is physiologically involved in the control of GH secretion in birds, in which it appears to inhibit GH release tonically. J. Endocr. (1986) 111, 91–97

Diurnal Variations of Plasma Growth Hormone and Brain Monoamines in Adult Male Rats

1973 ◽  
Vol 51 (12) ◽  
pp. 890-892 ◽  
Author(s):  
R. Collu ◽  
J. C. Jéquier ◽  
J. Letarte ◽  
G. Leboeuf ◽  
J. R. Ducharme
Keyword(s):  
Growth Hormone ◽  
Adult Male ◽  
Physiological Role ◽  
Male Rats ◽  
Male Rat ◽  
Plasma Growth Hormone ◽  
Gh Secretion ◽  
Adult Male Rat ◽  
Plasma Gh

Brain levels of monoamines (MA) in the adult male rat show a diurnal pattern of secretion with noradrenaline (NA) and serotonin (5-HT) reaching a peak at 1300 and 1800, respectively, and dopamine (DA) showing a bimodal pattern with peaks at 0500 and 1800. Plasma growth hormone (GH) values fluctuate widely during the nycthemeral period. Statistically significant correlations between plasma GH and brain MA levels, confirming the existence of a physiological role of MA in the control of GH secretion, could not be demonstrated in the present study.

Plasma growth hormone, somatostatin, insulin and glucagon inter-relationships during infusion of human pancreatic growth hormone-releasing factor in young and adult ducks (Anas platyrhynchos)

1987 ◽  
Vol 114 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Ch. Foltzer-Jourdainne ◽  
S. Harvey ◽  
H. Karmann ◽  
P. Mialhe
Keyword(s):  
Growth Hormone ◽  
Inhibitory Effect ◽  
Insulin Levels ◽  
Gh Secretion ◽  
Plasma Gh ◽  
Glucagon And Insulin ◽  
Rebound Increase ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Infusion Period

ABSTRACT Human pancreatic GH-releasing factor (hpGRF) increased the concentrations of plasma GH when infused i.v. into immature ducks. A dose-dependent increase in plasma GH was observed within 10 min of the start of infusion and was maintained during the 30-min infusion period. Simultaneous infusion of somatostatin S-14 prevented the increase in plasma GH induced by hpGRF, but when the infusion had finished there was a rebound increase in plasma GH. Infusion of the highest dose of hpGRF (800 ng/kg per min) in adult ducks had no significant effect on plasma GH. Plasma somatostatin concentrations were reduced during the infusion of hpGRF in young but not in adult ducks. This observation suggests that the stimulatory effect of hpGRF on GH secretion may be partly due to its inhibitory effect on somatostatin secretion. Infusion of hpGRF in ducklings also increased the concentrations of glucagon and decreased levels of insulin in the plasma. Peripheral plasma glucagon and insulin levels in adult ducks were unaffected by hpGRF infusion. These results indicate that in ducklings, hpGRF increases plasma GH and glucagon concentrations and lowers plasma somatostatin and insulin levels. In the adult, these hormonal responses to hpGRF are not maintained. The highly stimulatory effect of hpGRF on GH secretion in ducklings may explain why plasma GH concentrations are high in these birds. J. Endocr. (1987) 114, 25–32

scholarly journals Effects of repeated doses and continuous infusions of the growth hormone-releasing peptide hexarelin in conscious male rats

1998 ◽  
Vol 158 (3) ◽  
pp. 367-375 ◽  
Author(s):  
LK Conley ◽  
RC Gaillard ◽  
A Giustina ◽  
RS Brogan ◽  
WB Wehrenberg
Keyword(s):  
Adult Male ◽  
Plasma Corticosterone ◽  
Male Rats ◽  
Continuous Exposure ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Sprague Dawley Rats ◽  
Repeated Doses ◽  
The Mean ◽  
Plasma Gh

We have previously shown that hexarelin, a novel GH-releasing peptide (GHRP), is able to elicit GH release when administered i.v., s.c. or by mouth and that it is a more potent GH secretagogue than GHRP-6. In the current study, we investigated the effects of hexarelin administered as repeated doses at 2 h intervals or as a continuous 6, 30 or 174 h infusion to conscious male rats. In the first experiment, adult male Sprague-Dawley rats were prepared with dual indwelling jugular catheters. On the day of experimentation, these animals received three 25 micrograms/kg i.v. boluses of hexarelin at 2 h intervals with blood sampling at 5, 10, 15, 30, 60, 90 and 120 min after each dose. The mean peak GH response and the mean area under the GH response curve (AUC) for the 30 min after each administration were calculated and are reported as the mean +/- S.E.M. For both the peak and AUC results there was a significant (P < 0.05) difference in the GH response noted between the first (peak 301 +/- 37 ng/ml; AUC 5585 +/- 700 ng/ml per 30 min) and second (peak 149 +/- 47 ng/ml; AUC 3056 +/- 908 ng/ml per 30 min) injections of hexarelin, but not between the first and third (peak 214 +/- 49 ng/ml; AUC 3862 +/- 844 ng/ml per 30 min). In a second series of experiments, adult male Sprague-Dawley rats received continuous infusions (100 micrograms/h) of hexarelin or saline (1 ml/h) for 6, 30 or 174 h. Blood samples were collected every 20 min for the duration of the 6 h infusion and for the last 6 h of the two longer hexarelin infusions. Plasma GH concentrations peaked within 40 min of the initiation of infusion, but soon returned to basal levels. Mean plasma GH concentrations did not differ between any of the treatment groups, nor did any of the parameters of pulsatile hormone release analyzed. No significant differences in plasma corticosterone concentrations were noted between any of the treatment groups. On the other hand, while neither the 6 h (941 +/- 70 ng/ml) nor the 30 h (954 +/- 70 ng/ml) hexarelin infusions resulted in a significant increase in the plasma IGF-I concentrations over those noted in the saline controls (935 +/- 65 ng/ml), a 174 h hexarelin infusion did elicit a significant increase (1289 +/- 42 ng/ml; P < 0.05). Thus it appears that, while continuous exposure to hexarelin does not disrupt normal GH cycling, it may (after up to 174 h of exposure) alter other components of the growth axis. In addition, since the character of pulsatile GH release remained unaltered in response to the hexarelin infusion, it appears that this GHRP may not act by suppression of functional somatostatin tone as has been suggested previously.

EVIDENCE TO SUGGEST THAT RAT GROWTH HORMONE IS MODIFIED WHEN SECRETED BY THE PITUITARY GLAND

1979 ◽  
Vol 80 (1) ◽  
pp. 69-81 ◽  
Author(s):  
M. A. VODIAN ◽  
C. S. NICOLL
Keyword(s):  
Incubation Medium ◽  
Young Male ◽  
Inhibitory Effect ◽  
Male Rats ◽  
Dynamic State ◽  
Rat Tissues ◽  
Gh Secretion ◽  
Rat Growth ◽  
Highly Correlated

The relationships were examined between the concentrations of GH determined by bioassay (rat tibia test) and radioimmunoassay in homogenates of rat adenohypophysial tissue and in the incubation medium in which the tissue had been maintained. Adenohypophyses from young male rats were incubated in Medium 199 with or without a putative synthetic GH-releasing factor (GRF) to achieve a dynamic state of GH secretion, but the GRF did not consistently stimulate the release of GH as measured by either bioassay or radioimmunoassay. Both assays gave closely similar values for the concentration of GH in homogenates of the adenohypophyses of undisturbed rats. When the two assays were used to measure the concentrations of GH in incubated pituitary tissue, the values showed no correlation, although the concentrations of GH in the incubation medium were again highly correlated. However, the bioassay: radioimmunoassay ratio for the secreted hormone [2·14 ± 0·09 (s.e.m.)] was significantly higher than that for the intrapituitary form from the unincubated gland (0·93 ± 0·06). By radioimmunoassay, secreted rat GH was found to be less stable than purified rat GH when the two forms were incubated in vitro with slices of various rat tissues. Similarly, the rate of clearance of secreted rat GH from the plasma of hypophysectomized rats, as determined by radioimmunoassay, was much faster than that of the purified GH. The biological activity of purified bovine GH was blocked by aprotinin, an inhibitor of proteolysis, but the drug had no inhibitory effect on the bioactivity of rat GH secreted into the incubation medium. Overall, these results indicate that secreted rat GH has properties intermediate between those of the intrapituitary form and the form found in the circulation.

Influence of endogenous cholinergic tone and α-adrenergic pathways on growth hormone responses to His-d-Trp-Ala-Trp-d-Phe-Lys-NH2 in the dog

1993 ◽  
Vol 138 (2) ◽  
pp. 211-218 ◽  
Author(s):  
J. Muruais ◽  
A. Peñalva ◽  
C. Dieguez ◽  
F. F. Casanueva
Keyword(s):  
Growth Hormone ◽  
Inhibitory Effect ◽  
Adrenergic Agonist ◽  
Stimulatory Action ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Combined Administration ◽  
Cholinergic Tone ◽  
Basal Plasma ◽  
Plasma Gh

ABSTRACT His-d-Trp-Ala-Trp-d-Phe-Lys-NH2 (GHRP-6) is a synthetic peptide unrelated to any known hypothalamic-releasing hormone including growth hormone-releasing hormone (GHRH). Interestingly, this peptide induces a dose-related increase in plasma GH levels in all species tested so far. The aim of this study was to investigate the action of GHRP-6 alone or in combination with GHRH on GH release in dogs. In addition, the activation or blockade of endogenous cholinergic tone and α-1 adrenoceptors on GHRP-6-stimulated GH secretion was assessed. In adult Beagle dogs (n = 10), GHRP-6 (90 μg i.v.) increased basal GH levels from 2·6 ± 1·5 to 14·4 ± 3·1 μg/l (mean ± s.e.m.) after 15 min. GHRH (50 μg i.v.) induced a GH peak of 9·7 ± 2·2 μg/l at 15 min. The combined administration of GHRP-6 and GHRH strikingly potentiated canine GH release with a peak of 54 ± 9·0 μg/l (P <0·01). Pretreatment with the cholinergic agonist pyridostigmine (30 mg per os) increased GHRP-6-stimulated GH secretion (37·9 ± 10·1 μg/l P <0·05), while the muscarinic blocker atropine (100 μg i.v.) completely abolished (GH peak lower than 2 μg/l) the stimulatory action of GHRP-6. On the other hand, administration of the α-2 adrenergic agonist clonidine (4 pg/kg i.v.) increased basal plasma GH levels without affecting GH responses to GHRP-6. Finally, while the α-1 adrenergic agonist methoxamine (5 mg i.v.) did not significantly increase GH responses to GHRP-6, administration of the α-1 adrenoceptor antagonist prazosin (20 mg i.v.) reduced GHRP-6-induced GH secretion (area under curve, 206 ± 39 vs 557 ± 172, P <0·05). In summary, the synergistic effect of the combined administration of maximal doses of GHRP-6 and GHRH suggests that these two peptides act through different mechanisms. The finding that cholinergic drugs were able to modulate the GH secretion elicited by GHRP-6 argues against the hypothesis that such a peptide acts by influencing hypothalamic somatostatin release and suggests that it acts directly at the pituitary level. Finally, the unexpected lack of effect of clonidine and the inhibitory effect of prazosin on GHRP-6-induced GH secretion suggests that the role of α-adrenergic pathways in GH secretion is more complex than previously thought. Journal of Endocrinology (1993) 138, 211–218

Evidence for a primary involvement of somatostatin in clonidine-induced growth hormone release in conscious rats

1994 ◽  
Vol 141 (2) ◽  
pp. 259-266 ◽  
Author(s):  
R Lanzi ◽  
M Lapointe ◽  
W Gurd ◽  
G S Tannenbaum
Keyword(s):  
Male Rats ◽  
Hormone Release ◽  
Growth Hormone Release ◽  
Contrast Injection ◽  
Adrenergic Agonist ◽  
Conscious Rats ◽  
Gh Secretion ◽  
Behavioural Effects ◽  
Significant Regression ◽  
Plasma Gh

Abstract The GH-releasing activity of the α2-adrenergic agonist clonidine has been extensively studied in the rat, but the mechanism(s) by which clonidine stimulates GH release remains controversial. In the present study, we examined the effects of various doses of clonidine on spontaneous pulsatile GH secretion in conscious rats, and tested the hypothesis that the GH-releasing activity of clonidine is mediated primarily by an inhibition of hypothalamic somatostatin (SRIF) release. In the first experiment, free-moving adult male rats were given either saline or various doses of clonidine i.v. (30, 50 and 125 μg/kg) at times of spontaneous peaks (1100 h) and troughs (1300 h) in the GH rhythm. Clonidine, at all doses tested, failed to stimulate GH release when administered at the time of a spontaneous peak. In contrast, injection of clonidine at trough times (when SRIF tone is high) consistently augmented plasma GH levels (mean ± s.e.m. integrated GH release; 30 μg/kg, 1843·0±484·0; 50 μg/kg, 1469·0± 490·3; 125 μg/kg, 1675·6 ± 513·4 vs 201·3 ± 100·1 ng/ml per 45 min in saline-injected controls; P<0·05 or less). No significant regression was observed between increasing doses of clonidine and GH release. In the second experiment, i.v. administration of 30 μg clonidine/kg during a GH trough period, 30 min prior to GH-releasing factor (GRF) challenge, significantly potentiated the GH response to GRF compared with rats given saline (7218·7 ±806·6 vs 4206·9 ± 1068·1 ng/ml per 30 min; P<0·05). Clonidine treatment, at all doses tested, resulted in hyperglycaemia and behavioural effects. These results showed that: (1) clonidine is not a potent GH secretagogue in the rat; (2) when administered i.v., clonidine exerts a maximal GH-releasing activity already at the dose of 30 μg/kg; and (3) clonidine-induced GH release in the rat occurs mainly through an inhibition of hypothalamic SRIF release rather than by stimulating GRF secretion. Journal of Endocrinology (1994) 141, 259–266

CHOLINERGIC INFLUENCES ON HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL ACTIVITY OF STRESSED RATS: AN APPROACH UTILIZING AGONISTS AND ANTAGONISTS

1978 ◽  
Vol 89 (4) ◽  
pp. 726-736 ◽  
Author(s):  
N. Sithichoke ◽  
S. F. Marotta
Keyword(s):  
Stressed State ◽  
Cholinergic System ◽  
Plasma Corticosterone ◽  
Cholinergic Receptors ◽  
Male Rats ◽  
Central Effects ◽  
Adrenocortical Activity ◽  
Hpa Response ◽  
Stimulation Of ◽  
Auditory Stress

ABSTRACT Cholinergic involvement in the regulation of the hypothalamic-pituitary-adrenocortical (HPA) system of male rats was evaluated using muscarinic (atropine and methacholine) and nicotine (mecamylamine and nicotine) agents, which were selected for their specificity on cholinergic receptors (ChR). They were administered either intracerebroventricularly (icv) to produce central effects, or ip to produce both central and peripheral effects, prior to subjecting the animals to either auditory or hypercapnic stress for 1 h. Plasma corticosterone was used as an index of HPA activity. The results suggest that central muscarinic ChR are involved in inhibiting HPA activity in both non-stressed and stressed animals, whereas central nicotinic ChR are excitatory during stress but inactive in the non-stressed state. Stimulation of peripheral nicotinic ChR appeared to potentiate the HPA response to hypercapnia, and to inhibit the central excitatory nicotinic ChR when the latter were activated in non-stressed and auditory stressed rats. These data suggest that during auditory stress the HPA system is more dependent upon the cholinergic system for its activation than during non-stressed and hypercapnic states.

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