Laboratory of Animal Production, Department of Animal Science, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro 080, Japan
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ABSTRACT |
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The effect of cholinergic blockade on suppressed growth hormone
(GH) secretion caused by feeding or the intraruminal infusion of an
acetate, propionate, and butyrate mixture (107 and 214 µmol · kg1 · min
1
over 6 h) was examined in ovariectomized ewes. Intraruminal infusion at
the rate of 107 µmol · kg
1 · min
1
increased peripheral plasma short-chain fatty acid (SCFA)
concentrations to approximately the physiological levels noted after
feeding. Plasma GH was markedly suppressed by feeding and at both the
107 and 214 µmol · kg
1 · min
1
SCFA infusion rates; however, cholinergic blocking agents completely blocked the suppressed GH secretion after feeding and only at the 107 µmol · kg
1 · min
1
infusion rate. Plasma glucose increased at both infusion rates, and the
plasma free fatty acids decreased after feeding and at both infusion
rates. However, both metabolites were unchanged relative to the saline
control after the injection of the cholinergic antagonists. It is
suggested that the decrease in plasma GH observed after feeding and a
near-physiological ruminal SCFA increment is mediated via the
parasympathetic nerve and not by pharmacological ruminal SCFA
increments attributed to other pathways.
growth hormone; short-chain fatty acids; parasympathetic nerve
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INTRODUCTION |
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INHIBITORY EFFECTS of feeding on plasma growth hormone (GH) levels as well as GH-releasing factor (GRF)-induced GH responses have been reported in sheep (2, 14, 29) and goats (28). Trenkle (29) and Tindal et al. (28) found that feeding, anticipation of feeding, or artificial distention of the cranial sac of the rumen with a water-filled balloon reduced basal and GRF-induced GH secretion. These findings suggest that visual and mechanical stimuli accompanying feeding are involved in the mechanism causing the postprandial GH decrease. Moreover, because the action is very rapid, these findings also suggest involvement of a neural pathway. The vagus nerve is known to transmit signals from chemo- and mechanoreceptors existing in the rumen epithelium (11, 19), which could be a possible mechanism. However, Tindal et al. failed to demonstrate the involvement of the vagus nerve in the suppression of GH secretion after feeding after surgical cooling (28). Furthermore, because muscarinic receptor antagonists have been shown to abolish the rise in plasma GH stimulated by GH-releasing stimuli such as GRF in humans (10, 13), dogs (8, 9), and rats (6, 20), it is difficult to demonstrate that these stimuli also pass through the parasympathetic nerve, which can be blocked with cholinergic antagonists by pharmacological methods. However, scopolamine-N-butyl bromide, a muscarinic receptor antagonist that is a quaternary ammonium derivative unable to pass the blood-brain barrier (BBB), failed to alter GH release by GH-releasing stimuli in the dog (8, 9). This result suggests that cholinergic muscarinic receptors located in the central nervous system, inside the BBB, play a promoting role in GH release and that muscarinic receptor antagonists have no direct effect on the pituitary (24). These conclusions are supported by the fact that, although the existence of muscarinic receptors in the anterior pituitary of sheep (7) and rats (23) has been detected by the binding of [3H]quinuclidinyl benzilate, a potent and specific muscarinic antagonist, acetylcholine does not stimulate the release of GH from perifused rat adenohypophyses (18). Likewise, nicotinic receptors have no effect on the GH secretion mechanism independent of penetrating BBB (24). This conclusion is supported by the fact that nicotine, one of the nicotinic receptor agonists (tertiary amine derivative), and mecamylamine, one of the nicotinic receptor antagonists (secondary amine derivative), have no effect on GH secretion, although these drugs easily penetrate the BBB (8). Therefore, it is possible to block the parasympathetic nerve without effects on the GH secretion mechanism by using scopolamine-N-butyl bromide and a nicotinic antagonist.
Other mechanisms for this inhibitory effect after feeding have been proposed. In our previous study we demonstrated that intravenous infusion of propionate or butyrate suppressed GRF-induced GH secretion in sheep (22). In addition to this, intraruminal infusion of short-chain fatty acids (SCFA) at a physiological rate, as high as the levels observed after a meal, suppressed plasma GH in sheep (21). Thus SCFA are also supposed to play a role in regulating GH secretion after feeding in ruminants.
We therefore examined in detail the effects of blocking the parasympathetic nerve, using cholinergic antagonists, on suppressed GH secretion by feeding and intraruminal SCFA infusion.
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MATERIALS AND METHODS |
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Animals. Six adult ovariectomized ewes (54-64 kg) were used. The ewes were housed in metabolic cages and offered alfalfa pellets at 2% of body weight in a single meal at 1200. Water was available continuously. At least 1 mo before experiments began, a rumen cannula (Flexible Rumen Cannula, no. 7C, Bar Diamond, Yokohama, Japan) was fitted to each animal under general anesthesia with pentobarbital sodium (25 mg/kg, Nembutal injection, Abbott, North Chicago, IL). At least 1 wk before the experiments, polyethylene catheters (IVH catheter kit, Terumo, Tokyo, Japan) for sampling and injection were inserted into each jugular vein through a hypodermic needle. The catheters were kept patent by daily flushing with a sterile solution of trisodium citrate (3.8 g/100 ml). All animal-based procedures were in accordance with the "Guidelines for the Care and Use of Experimental Animals of Obihiro University of Agriculture and Veterinary Medicine," which were formulated from the "Declaration of Helsinki and Guiding Principles in the Care and Use of Animals" (1).
Feeding experiment.
Experiments were carried out from 1000 (2 h) to 1600 (4 h) and
performed at 7-day intervals. The ewes were fed at 1200 (0 h). All ewes
completely finished eating within 1 h of being fed. At 1400 (2 h) the
ewes were intravenously injected through one catheter with a 3-ml
volume of scopolamine-N-butyl bromide
(0.08 mg/kg, Sparicon, Yamanouchi Pharmacy, Tokyo, Japan) (9) and hexamethonium bromide (10 mg/kg, Wako Pure Chemical, Osaka, Japan) (5)
dissolved in sterile saline. For the control, injections were carried
out using the same volume of saline. Samples of venous blood were
collected at 15-min intervals. In addition, ruminal fluid samples were
collected at 0900 and 1600 to avoid mechanical stimuli for the rumen
during blood sampling.
Intraruminal infusion experiment.
Experiments were carried out from 1000 (2 h) to 1800 (6 h) and
performed at 7-day intervals. Cholinergic receptor antagonists were
intravenously injected at the same rate as for the feeding experiment
at 1600 (4 h). The control injection was carried out using the same
volume of saline. To assess the effect of the ruminal infusion of the
SCFA mixture on GH secretion, a mixture of sodium acetate, propionate,
and n-butyrate (molar ratio of each
acid respectively 70:20:10, adjusted to pH 4.5 with sodium hydroxide) were infused over a period of 6 h, starting at 1200 (0 h), at the rates
of 107 or 214 µmol · kg
1 · min
1
with the use of a constant infusion pump (1 ml/min). The 107 µmol · kg
1 · min
1
infusion rate causes a rumen SCFA concentration similar to
physiological levels (21). Samples of venous blood were collected at
15-min intervals. In addition, ruminal fluid samples were collected at 0900 and 1800.
Analyses.
Blood samples collected in heparinized syringes were immediately
transferred into polyethylene test tubes, cooled on ice water, and
centrifuged at 4°C. A portion of plasma was stored at
25°C for GH, glucose, and free fatty acid (FFA) assays. The
GH assay was performed as described previously (21, 22). Briefly, GH was assayed by a double-antibody method using ovine GH antiserum [National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) anti-oGH-2, AFP-C0123080] and GH standards (NIDDK
oGH-I-4, AFP-8758C). Ovine GH (NIDDK oGH-I-4, AFP-8758C) was iodinated using the chloramine T method. The assay had a minimum-detectable concentration of 0.098 ng/ml. Inter- and intra-assay coefficients of
variation were 6.3 and 6.3%, respectively. Plasma glucose was determined by the glucose-oxidase method (glucose CII-Test Wako, Wako
Pure Chemical). Plasma FFA were determined by the acyl-CoA synthase · acyl-CoA oxidase method
[nonesterified fatty acids (NEFA) C-Test Wako, Wako Pure
Chemical]. Plasma and ruminal fluid were mixed with a one-half volume
of a 25% metaphosphoric acid solution containing crotonic acid (25 mmol/l) as internal standard and were stored at
25°C until
volatile fatty acid (VFA) assay. VFA concentrations were determined
using a gas chromatographic technique (163, Hitachi, Tokyo, Japan). The
length and internal diameter of the column used for the analysis were 2 m and 3 mm, respectively. The rate of flow of the carrier
gas (N2) was 20 ml/min, and the
oven temperature was 145°C.
Statistics.
Mean values as well as the standard errors of the means were
calculated. The area under the curve (AUC) of GH and the mean for the
other data were calculated for the three (feeding experiment) or four
(intraruminal infusion experiment) 2-h periods [for the feeding
experiment: the period before feeding (between 2 and 0 h), the
period after feeding before injection of the cholinergic antagonists
(between 0 and 2 h), and the period after feeding after cholinergic
antagonist injection (between 2 and 4 h); and for the infusion
experiment: the period before infusion of SCFA (between
2 and 0 h), the first period of SCFA infusion before injection of the
cholinergic antagonists (between 0 and 2 h), the second period of SCFA
infusion before cholinergic antagonist injection (between 2 and 4 h),
and during SCFA infusion after cholinergic antagonist injection
(between 4 and 6 h)]. Significant differences between periods
within each treatment were analyzed by analysis of variance, using the
general linear model procedure of the SAS program package (SAS
Institute, Cary, NC) on the GH AUC or the mean for the other data
followed by Dunnett's test for comparing all treatments with the
control test. The significance of differences between the control and
treatments within the same period for the increase in GH AUC and mean
values above basal values (
2 to 0 h) were analyzed by analysis
of variance. The ruminal and plasma SCFA concentration data were
analyzed by analysis of variance comparing all infusions with feeding
by using Dunnett's test.
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RESULTS |
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Feeding experiment.
The time course for the GH response is represented in Fig.
1. The mean basal concentration of plasma
GH before the onset of feeding (2-0 h) was 3.1 ± 0.5 and 3.2 ± 0.7 ng/ml for the control and cholinergic antagonist
injection experiments, respectively. GH concentration was reduced to
<1 ng/ml until 2 h after the onset of feeding. The mean concentration
of GH was immediately enhanced to 5.2 ± 0.9 ng/ml between 2 and
4 h after the injection of cholinergic antagonists. However, the plasma
GH concentration remained at low levels after the saline injection (1.6 ± 0.4 ng/ml). The GH AUC for the antagonist injection was
significantly reduced to 121.8 ± 18.0 ng · ml
1 · min
1
(P < 0.05) between 0 and 2 h
relative to the basal levels (
2-0 h; 370.8 ± 60.1 ng · ml
1 · min
1).
However, GH AUC was significantly increased to 600.6 ± 110.4 ng · ml
1 · min
1
by injection of the cholinergic antagonists between 2 and 4 h postfeeding, whereas the GH AUC for the control injection was significantly reduced (100.2 ± 14.3 and 187.4 ± 50.4 ng · ml
1 · min
1
for the 0- to 2-h and 2- to 4-h periods, respectively;
P < 0.05) relative to the basal
value (
2-0 h; 369.5 ± 89.7 ng · ml
1 · min
1).
Additionally, the AUC above basal values after injection of the
antagonists was significantly higher than that of the control injection
value (P = 0.0032). After feeding
there was an immediate tendency for the glucose concentration to
decrease, followed by a gradual increase (Fig. 1). However, these
trends did not reach statistical significance between periods within
each treatment. In addition, there was no significant difference
(2-4 h) between control and cholinergic antagonist treatment with
respect to the increase in the mean value above basal values. Plasma
FFA concentration gradually decreased after feeding, regardless of the
injection treatment (Fig. 1). The mean concentration for the control
injection significantly decreased to 0.107 ± 0.007 and 0.058 ± 0.005 meq/l (P < 0.05) compared with
the basal value (
2-0 h; 0.221 ± 0.020 meq/l) for the 0- to 2-h and 2- to 4-h periods, respectively. Similarly, plasma FFA for
the cholinergic antagonist injection was significantly reduced to 0.197 ± 0.035 and 0.092 ± 0.026 meq/l (P < 0.05) compared with the basal
value (
2-0 h; 0.265 ± 0.033 meq/l) at the 0- to 2-h and
2- to 4-h periods, respectively. However, there was no significant
difference (2-4 h) between the control and cholinergic antagonist
injection for the AUC above basal values.
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SCFA infusion (107 µmol · kg1 · min
1)
plus cholinergic blocker.
The time course for the GH response for the 107 µmol · kg
1 · min
1
infusion experiment is presented in Fig. 2.
The mean basal concentrations of plasma GH before 107 µmol · kg
1 · min
1
SCFA infusion began (
2-0 h) were 5.3 ± 1.0 and 4.5 ± 0.9 ng/ml for the control and cholinergic antagonist injections,
respectively. GH concentrations were gradually suppressed during the 4 h of the SCFA infusion. After the cholinergic antagonist injection, however, the plasma GH concentration immediately increased to 6.4 ± 2.1 ng/ml. GH concentrations remained in the suppressed state after the
saline injection (2.8 ± 0.7 ng/ml). The GH AUC was not
significantly different between the periods for the cholinergic antagonist injection. However, the GH AUC for the control injection significantly decreased to 372.7 ± 79.7 and 322.8 ± 73.4 ng · ml
1 · min
1
(P < 0.05) from the basal value
(
2-0 h; 618.9 ± 115.9 ng · ml
1 · min
1)
during the 2- to 4-h and 4- to 6-h periods, respectively. The incremental area minus basal values for the cholinergic antagonist treatment after injection was significantly greater than that for the
saline injection value (P = 0.0455). Plasma glucose concentrations gradually increased after the
start of the SCFA infusions (Fig. 2). However, cholinergic receptor
antagonists had little effect on the plasma glucose concentration. The
mean plasma glucose concentration for the control injection increased
to 59.3 ± 2.5 and 64.0 ± 3.1 mg/100 ml relative to the basal
value (
2-0 h; 51.9 ± 2.4 mg/100 ml) during the 2- to
4-h and 4- to 6-h periods for the 107 µmol · kg
1 · min
1
SCFA infusion, respectively. Similarly, the mean concentration of
glucose significantly increased to 63.4 ± 3.7 mg/100 ml (4-6 h) compared with the basal value (
2-0 h; 54.2 ± 1.6 mg/100 ml) for the cholinergic antagonist injection during the 107 µmol · kg
1 · min
1
SCFA infusion. However, there was no significant difference (4-6 h) between the saline and cholinergic antagonist injection experiments with respect to the increment of mean glucose concentrations from the
baseline. Plasma FFA concentrations were gradually reduced after the
start of the SCFA infusion, and this trend continued soon after the
control and treatment injections (Fig. 2). Plasma FFA concentrations
for the saline injection significantly decreased to 0.062 ± 0.015 meq/l (4-6 h; P < 0.05)
compared with the basal value (
2-0 h; 0.314 ± 0.053 meq/l). Similarly, the mean FFA concentration for the cholinergic
antagonists experiment was significantly reduced to 0.095 ± 0.017 and 0.060 ± 0.012 meq/l (P < 0.05) compared with the basal value (
2-0 h; 0.201 ± 0.025 meq/l) in the 2- to 4-h and 4- to 6-h periods, respectively.
However, there was no significant difference (2-4 h) between
the control and cholinergic antagonist injection in the difference of
the mean value from the baseline.
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SCFA infusion (214 µmol · kg1 · min
1)
plus cholinergic blocker.
The time course for the GH response for the 214 µmol · kg
1 · min
1
infusion experiment is presented in Fig. 2. The mean basal
concentrations of plasma GH before the 214 µmol · kg
1 · min
1
SCFA infusion began (
2-0 h) were 5.2 ± 0.8 and 5.0 ± 0.6 ng/ml for the control and cholinergic antagonists injections,
respectively. GH concentrations gradually decreased during the 4 h of
the SCFA infusion. However, cholinergic receptor antagonists had little effect on the plasma GH concentration. The mean concentrations were 1.1 ± 0.3 and 1.3 ± 0.2 ng/ml for the saline and cholinergic blocker injections, respectively. The GH AUC for the control injection was significantly reduced to 147.6 ± 45.6 ng · ml
1 · min
1
(4-6 h; P < 0.05) relative to
the basal value (
2-0 h; 585.1 ± 104.6 ng · ml
1 · min
1).
Similarly, the GH AUC for the blocker injection was also significantly reduced to 161.6 ± 28.4 ng · ml
1 · min
1
(4-6 h; P < 0.05) relative to
the basal value (
2-0 h; 554.6 ± 92.9 ng · ml
1 · min
1).
The incremental area minus basal values after the control and antagonists injections were not significantly different. The mean plasma glucose concentration gradually increased after the onset of the
SCFA infusion (Fig. 2). However, the cholinergic antagonists had no
significant effect on this increase. The mean glucose concentration for
the control experiment increased to 66.7 ± 2.0 and 75.2 ± 3.3 mg/100 ml compared with the basal value (
2-0 h; 60.0 ± 2.3 mg/100 ml) at the 2- to 4-h and 4- to 6-h periods,
respectively. Similarly, the mean concentration of glucose for the
antagonist experiment was significantly increased to 65.9 ± 2.2 and
72.1 ± 3.4 mg/100 ml compared with the basal value (
2-0
h; 54.2 ± 1.6 mg/100 ml) at 2- to 4-h and 4- to 6-h periods,
respectively. However, there was no significant difference (4-6 h)
between saline and cholinergic antagonist injections for the increment
of glucose concentrations above the baseline. Plasma FFA concentrations
were gradually reduced after the start of the SCFA infusion, and
injection of the cholinergic blocker did not change the concentration
of plasma FFA. This is in contrast to the saline injection, which apparently caused a small increase in FFA concentrations (Fig. 2). The
mean FFA concentration for the control experiment significantly decreased to 0.101 ± 0.021 and 0.070 ± 0.011 meq/l
(P < 0.05) compared with the basal
value (
2-0 h; 0.163 ± 0.017 meq/l) in the 2- to 4-h and
4- to 6-h periods, respectively. Plasma FFA for the antagonist
experiment was also significantly reduced to 0.080 ± 0.011 meq/l
(4-6 h; P < 0.05) compared with
the basal value (
2-0 h; 0.155 ± 0.012 meq/l). In
addition, there was no significant difference (2-4 h) between
control and antagonist experiments for the increment of mean FFA values
compared with the baseline.
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DISCUSSION |
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This experiment demonstrates that feeding and the intraruminal infusion of SCFA to cause a rumen SCFA content at near-physiological levels except for above pharmacological levels caused suppression of GH secretion via the parasympathetic nerve.
Inhibition of plasma GH levels and the GRF-induced GH response after feeding have been reported in sheep (2, 14, 29) and goats (28). Trenkle (29) demonstrated a clear and chronic reduction in GH secretion within 30 min after feeding in sheep by estimating the magnitude of the GH response to GRF. He further demonstrated that both distention of the rumen and the anticipation of being fed each rapidly reduced the GH response to the intravenous injection GRF but that basal plasma GH concentrations remained unchanged in sheep. Tindal et al. (28) also observed that artificial distention of the cranial sac of the rumen with a water-filled balloon and the anticipation of being fed each caused an immediate decline in the plasma GH concentration in goats. Additionally, when lambs drank milk diluted with water or vigorously ate chopped lucerne hay or when adult wether sheep ate dry feed rapidly or were fitted with an esophageal fistula and were sham fed, the plasma GH level declined rapidly (4). These data suggest that mechanical or visual stimuli at ingestion of feed via some neural pathway may be one of the factors causing the immediate suppression of GH secretion by the somatotroph, either directly and/or by other neuropeptides released in the hypothalamus after feeding. The vagus nerve is known to transmit signals from chemo- and mechanoreceptors existing in the rumen epithelium (11, 19), which could be a possible mechanism. Tindal et al. investigated the role of visceral stimuli in the regulation of GH release in castrated male goats by bilateral cooling of exteriorized vagi. However, it was not possible to determine whether bilateral cooling of the vagi was able to block transmission of afferent impulses that inhibit release of GH, because the stress associated with cooling-induced paralysis of the swallowing mechanism itself may have suppressed GH release. In addition, the stress associated with accidental embolism was also found to inhibit GH release. Therefore, it is difficult to demonstrate the control GH release by this mechanism with surgical methods. However, in the present experiment, we clearly demonstrated that GH release is mediated via the parasympathetic nervous system by a pharmacological method, although we cannot stipulate that this mechanism is mediated via the vagus nerve.
It is interesting that the blocking action of the cholinergic
antagonists was observed only during the 107 µmol · kg1 · min
1
infusion rate. As plasma glucose significantly increased during the 107 µmol · kg
1 · min
1
infusion rate compared with the basal value (
2 to 0 h), the 107 µmol · kg
1 · min
1
infusion rate obviously exceeded physiological concentrations after
feeding (12). However, in sheep, feeding once per day, as in the
present study, commonly raises the ruminal SCFA concentration up to
120-200 mmol/l at 2 h after the onset of feeding (16). In
addition, because the SCFA concentration of the rumen and especially that of the plasma after the 107 µmol · kg
1 · min
1
SCFA infusion were not significantly different from that observed after
feeding, it is suggested that this infusion rate only slightly exceeded
what would be physiologically normal. However, the plasma glucose
concentration was significantly increased by the 214 µmol · kg
1 · min
1
SCFA infusion rate relative to the basal values (
2-0 h) and the SCFA concentration of ruminal fluid and plasma after infusion was
significantly increased by this infusion rate relative to after
feeding. In this case, the ewes were infused with SCFA at a
pharmacological rate. Thus there was a clearly significant difference in the rumen fluid and plasma SCFA concentration between the two infusion rates. Recently, Ishiwata et al. (17) suggested that propionate and butyrate have an inhibitory effect on GRF-induced GH
release from goat in primary cultured anterior pituitary cells. Therefore, it is possible that the increase of SCFA in peripheral blood
had a direct effect on the pituitary during the 214 µmol · kg
1 · min
1
infusion rate. In addition, the pituitary is not the site of action of
the cholinergic antagonist, because muscarinic antagonists in
particular are known to have no effect on pituitary GH secretion (8,
9). This assumption was supported by the fact that
scopolamine-N-butyl bromide, which was
used in this study, has been shown to have no direct effects on the
pituitary outside of the BBB with respect to GH secretion (24).
Consequently, antagonists may be unsuccessful in blocking the direct
suppression of GH secretion from the pituitary, apparently caused by
the increase in peripheral blood SCFA after a SCFA infusion in the
pharmacological range. Furthermore, it is likely that the direct
inhibitory effects of peripheral blood SCFA on pituitary GH secretion
overcame the GH-releasing effect of the cholinergic antagonists
blocking the parasympathetic nervous system. However, it is possible
that the signals stimulated by the intraruminal SCFA infusion were
transmitted by the vagus nerve from chemoreceptors in the rumen
epithelium to brain centers above the pituitary level during the 107 µmol · kg
1 · min
1
infusion rate, as for the feeding experiment. Therefore, these results
may indicate that increment of SCFA concentration in the rumen acts as
one of the factors on the suppression of GH secretion after feeding in
sheep.
In the present experiment, plasma glucose was unchanged after feeding, although there was a trend for an initial decrease that was then followed by an increase. Plasma FFA was significantly reduced by feeding. These trends and significant difference agree with the previous study of Bassett (3). In the case of glucose, it is possible that the sampling time in the present study was too short for the fermentation in the rumen to provide the glucose precursors required to cause an increase in glucose levels for the fermentation in the rumen after feeding (3, 16). On the other hand, intraruminal infusion of SCFA caused hyperglycemia and suppression of the FFA concentration. These changes in metabolite concentration also agree with previous studies (4, 12), although the increase in plasma glucose was not significant in the experiment of deJong (12) using goats infused with SCFA at an infusion rate similar to that of the present study. Glucose and FFA concentrations have been reported to affect GH secretion in ruminants (15, 26). However, the cholinergic blocker had no significant effect on the plasma glucose and FFA concentrations, although it increased GH secretion in the present investigation. Therefore, the possible involvement of these metabolites in the suppression of GH secretion after feeding and intraruminal infusion of SCFA can be excluded.
In ruminant animals, it has been reported that long-term nutritional status affects GH and IGF-I secretion in addition to the effect of acute feeding. Although the reports detailing these mechanisms are conflicting, it has been suggested that the mechanism is mediated by neural peptides such as GRF or somatostatin at the level of the hypothalamus (1a, 27). From the results of the present study, we suggest that the stimulus of acute feeding in the alimentary tract is transmitted to the pituitary level. Therefore, a further detailed study of the mechanism by which GH secretion is suppressed by feeding in ruminants above the level of the pituitary is required.
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ACKNOWLEDGEMENTS |
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We are grateful to Dr. M. T. Rose (Japanese Institute of Animal Industry, Tsukuba) for valuable advice on this manuscript. We thank the National Hormone and Pituitary Program (of the National Institute of Diabetes and Digestive and Kidney Diseases) for providing ovine GH antiserum and antigen.
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FOOTNOTES |
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Address for reprint requests: N. Matsunaga, Laboratory of Animal Production, Dept. of Animal Science, Obihiro Univ. of Agriculture and Veterinary Medicine, Inada-cho, Obihiro 080, Japan.
Received 30 April 1997; accepted in final form 18 September 1997.
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