Infusion Of Growth Hormone Releasing Factor Research Articles

Pulsatile infusion of growth hormone-releasing factor depresses growth of young broiler chickens

This study was conducted to determine the effects of programmed intravenous infusion of growth hormone-releasing factor (GRF) on the growth and metabolism of young broiler chickens (4–7 weeks of age). Twelve 4-week-old chickens, fitted with jugular catheters, were randomly assigned to three treatment groups (four birds/group): pulsed infusion of saline [SAL-P] at 3 hr intervals, pulsed infusion of GRF 1–44 (5μg/kg at 3 hr intervals)(GRF-P], or continuous infusion of GRF (40 μg/kg-day)(GRF-C]. The GRF-P treatment depressed ( P < 0.05) average daily gain by 32%, average daily feed consumption by 24%, and final body weight by 17% when compared with the SAL-P group. Pulsatile infusion of GRF (GRF-P) reduced ( P < 0.05) abdominal fat weight by 39% and body fat content by 28% when compared to the SAL-P group. Plasma GH levels were elevated ( P < 0.05) 2.1-fold in the GRF-P group at 15 min-post-infusion, while GH levels in the GRF-C group were maintained about 70% higher than those in the SAL-P group. Plasma levels of insulin-like growth factor-I (IGF-I) were consistently lower in the GRF-P group at all ages. There were no significant differences in plasma levels of triiodothyronine (T 3), thyroxine (T 4), insulin, or glucose among treatment groups. This study shows that pulsatile infusion of GRF, designed to enhance plasma GH levels, does not improve growth rate, feed efficiency, or body composition of young broiler chickens.

The effects of growth hormone-releasing factor on food consumption in anorexia nervosa patients and normals

Current evidence from animal studies indicate that growth hormone-releasing factor (GRF) has direct effects on mechanisms controlling eating behavior. There is also evidence that eating disorder patients have abnormalities in their GRF-growth hormone (GH) axis. The present study investigated the possibility that GRF abnormalities contribute to the expression of abnormal eating patterns in anorexia nervosa (AN) patients, and that GRF has therapeutic potential in this regard. To this end, patients diagnosed with anorexia nervosa or combined anorexia nervosa/bulimia nervosa (AN/BN), as well as normal female subjects, were tested for their eating and GH responses following intravenous infusion of GRF (1 μg/kg) or placebo. Results indicated that GRF stimulates food consumption in AN patients and attenuates the elevated food consumption in AN/BN patients. These results are consistent with the notion that GRF abnormalities contribute to abnormal eating behavior, and provide preliminary evidence for the therapeutic potential of GRF in such conditions. The extent to which the present effects of GRF are dependent on nutritional status, GH actions, or direct central actions of GRF, are discussed.

Effect of growth hormone-releasing factor infusion on somatotropin, prolactin, thyroxine, insulin, insulin-like growth factor I and blood metabolites in control and somatostatin-immunized growing pigs

The aim of this study was to characterize the effects of prolonged infusion of growth hormone-releasing factor (1–29)NH 2 (GRF) on plasma concentrations of hormones and metabolites when administered to control pigs and pigs immunized against somatostatin (SRIF). In the first experiment, eight purebred Yorkshire boars averaging 113 ± 2 kg BW were immunized against SRIF conjugated to bovine serum albumin (BSA) (n = 4) or BSA alone (n = 4). Somatotropin (ST) response to four rates of GRF infusion (0, 1.66, 5 and 15 ng/min/kg BW) for 6 hr was evaluated using a double balanced 4 × 4 Latin square design. During the 4 hr before infusion, SRIF-immunized animals tended (P = 0.06) to have a higher ST release (613 vs 316 ng · min/ml, SE = 232) than controls. During infusion, GRF elicited a dose-dependent increase in ST release in both squares; the ST response was not better in SRIF-immunized animals than in controls (P > 0.05) (1435 vs 880 ng · min/ml; SE = 597). In the second experiment, ten purebred Yorkshire boars (5 controls and 5 SRIF-immunized animals) averaging 69 ± 2 kg BW were continuously infused with GRF at the rate of 15 ng/min/kg BW for six consecutive d. Under GRF infusion, ST concentrations increased (P < 0.05) from 805 to 4768 ng · min/ml (SE = 507) from day 1 to day 6 in both SRIF-immunized and control animals. Prolactin levels increased (P < 0.05) with GRF infusion; pattern of increase was different (P<.01) overtime in control and SRIF-immunized animals. Thyroxine levels increased from 2.53 to 3.45 μg/dl (SE = 0.16) after six d of infusion. Insulin-like growth factor I was higher (P<0.05) before (139 vs 90 ng/ml; SE = 11) and during (222 vs 185 ng/ml; SE = 11) GRF infusion in SRIF-immunized animals. A transient increase (P < 0.05) in glucose and insulin was observed in both groups. Immunization against SRIF had no effect on blood metabolites; however, GRF infusion increased free fatty acids from 157 to 204 μEq/l (SE = 11) and decreased blood urea nitrogen from 4.1 to 3.5 mmol/l (SE = 0.2) from day 1 to day 6, respectively. In summary, active immunization against SRIF in growing pigs increased ST and IGF-I concentrations. Infusion of GRF continuously raised ST levels with days of infusion without any sign of decrease responsiveness.

Blunted growth hormone response to peripheral infusion of human growth hormone-releasing factor in patients with panic disorder

Patients with panic disorder (N = 11) and age- and sex-matched normal control subjects (N = 11) were challenged with human growth hormone-releasing factor (GH-RF) (1 microgram/kg i.v.) or placebo in random order. The control subjects had significantly increased plasma growth hormone (GH) levels after GH-RF infusion whereas panic disorder patients did not. At 15 and 30 minutes after GH-RF infusion, GH concentrations were significantly higher in the control subjects than in the patients. These findings with GH-RF extend findings from earlier reports that patients with panic disorder show blunted GH response to phobic stimulation and clonidine.

Effect of α-methyl-p-tyrosine and an antiserum to rat growth hormone (GH)-releasing factor (GRF) on plasma GH secretory profile during a continuous infusion of human GRF in rats

The effects of α-methyl-p-tyrosine (α-MT) and an antiserum specific to rat growth hormone-releasing factor (GRF) on growth hormone (GH) secretory profile during a 6-h continuous infusion of human GRF(1–44)NH 2 were observed in unrestrained adult male Wistar rats. All rats were provided with two indwelling cannulae: one in the right atrium for undisturbed blood collection and the other in the inferior vena cava for 0.9% NaCl or GRF infusion. GRF was administered by an infusion pump at a dose of 50 ng/kg b.wt./min for 6 h. Serial blood specimens were withdrawn every 20 min. In control rats, episodic GH secretion occured every 170 min and plasma GH levels during baseline period were low with little fluctuation. GH secretion was augmented significantly during continuous GRF infusion in control rats but interpeak intervals remained unaltered. When an antiserum specific to rat GRF was administered, episodic GH secretion was abolished. In these rats, pulsatile GH secretion indistinguishable from that of control rats was observed in the continuous presence of human GRF. Although α-MT inhibited episodic GH secretion, α-MT-treated rats exhibited high-frequency, low-amplitude episodic GH secretion and elevated baseline levels during the stimulation. There were no differences in the amount of GH secreted during GRF infusion between rats that had received either α-MT or antiserum to rat GRF. Since GH secretion to GRF is determined largely by somatostatin, the results suggest that phasic release of somatostatin plays an important role in determining the rhythmicity of episodic GH secretion, and that is modulated by α-MT but not by the immunoneutralization of GRF.

Human growth hormone releasing factor infusion effects on plasma growth hormone in affective disorder patients and normal controls

In a preliminary, prospective pilot study, five patients with major depressive disorder and eleven age and sex matched normal controls received intravenous human growth hormone releasing factor (hGRF) (1 microgram/kg in 5 cc of normal saline infused over five minutes) and placebo. Thirty minutes after insertion of the catheter, blood was sampled every 15 minutes for thirty minutes prior to and for 2 hours subsequent to intravenous infusion of hGRF or placebo. hGRF but not placebo caused significant elevations of plasma growth hormone levels in all subjects. Of interest, the depressed patients had a significantly attenuated rise in plasma growth hormone concentrations when compared with the normal controls. These results must be considered preliminary awaiting replication with a larger subject population.

Serum growth hormone and nitrogen metabolism responses in young bull calves infused with growth hormone-releasing factor for 20 days

Intravenous infusion of growth hormone (GH)-releasing factor (GRF) sustains elevated serum GH for at least 5 days in young Holstein steers, but the effects of extended infusion of GRF on serum GH and nitrogen (N) metabolism have not been determined. Thirteen Dutch-Friesian bull calves (148 ± 1.5 kg) were assigned randomly to receive daily either 0 or 3.6 mg GRF (hGRF 1–44NH 2; U-68420) in saline as a continuous infusion for 20 days. Calves were fed milk replacer twice daily while housed indoors in wooden-slatted floor box crates (metabolism cages). Nitrogen determinations were made on daily feed, feces, and urine samples which were pooled for days 9 to 14 of treatment. Concentrations of GH were quantified in blood samples collected at 20 min intervals for 8 hr on day 1, 10 and 20. The infusion of GRF increased baseline GH (P<.07), the number of GH pulses (P<.0001), the amplitude of the GH pulses (P<.001), and area under the GH response curve (P<.0002). Within GRF-infused calves baseline GH (P<.0001) and area under the GH response curve (P<.006) were greater on day 20 than on day 1 or 10 (day × treatment interaction, P<.04). Area under the GH response curve was similar on each sampling day in saline-infused calves, but baseline GH was higher (P<.03) on day 20 than either day 1 or 10. Infusion of GRF increased episodic GH secretion in spite of limited pulsatile activity in saline-infused calves. On days 9–14, infusion of GRF decreased the excretion of urinary N (P<.02) and improved N balance (P<.04) without affecting N intake, fecal N, or the coefficient of N digestibility compared to saline-infused calves. In the present study, GRF administered as a continuous iv infusion for 20 days maintained elevated serum GH concentrations, conserved the episodic GH pattern, and improved N balance in young bull calves. The findings that (1) the pituitary does not become refractory to continued exposure to GRF and (2) a positive effect on N metabolism clearly make GRF or an analog an attractive alternative to exogenous GH as a means to improve animal production.

Does growth hormone releasing factor desensitize the somatotroph? Interpretation of responses of growth hormone during and after 10-hour infusion of GRF 1-29 amide in man.

It is unclear whether growth hormone releasing factor (GRF) administration in vivo may desensitize the somatotroph. To investigate this possibility we have examined the effects of 10-h infusion of the equipotent 1-29 amide analogue of hpGRF on serum GH levels and on the subsequent GH response to a bolus dose of GRF (1-29). Four normal adult males received an intravenous infusion of 1-29 GRF (1 microgram/kg/h) from 0800 to 1800 h, with blood samples taken at 10 min intervals. A 100 micrograms intravenous bolus dose of GRF was given at 1800 h, and sampling continued for a further 90 min. GH levels were near or below the limit of detection (0.5 mU/l) throughout the control 10 h period. During GRF infusion there was increased GH release with pulses of irregular frequency and amplitude (up to 80 mU/l) continuing throughout the entire infusion period. There was no apparent reduction in total GH released towards the latter part of the infusion. On the control day, 100 micrograms GRF bolus increased mean (+/- SEM) GH from 0.82 +/- 0.21 mU/l to a peak of 59.0 +/- 44.8 mU/l (P less than 0.002). Following 10-GRF infusion, responses to bolus injection of GRF were reduced, but variable. In two subjects a small rise in GH levels occurred (basal 6.4 and 7.2 rising to peak values of 11.2 and 23.0 mU/l respectively). In the other two subjects, GH levels fell but in these the GRF bolus had coincided with a GH peak. The loss of GRF responsiveness after GRF infusion may be due to 'desensitization'.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous infusion of growth hormone-releasing factor: effects on pulsatile growth hormone secretion in normal rats.

The effects of a continuous infusion of growth hormone-releasing factor (GRF) on pulsatile growth hormone (GH) secretion were studied in conscious, freely moving rats. Male Sprague-Dawley rats were prepared with 2 indwelling venous catheters and were then housed individually for 6-16 days in isolation chambers. After this period, normal saline, 1.5 microgram/h GRF or 15 micrograms/h GRF were continuously infused for 8 or 31 h via one of the catheters. Blood samples were drawn at approximately 20-min intervals via the other catheter during the last 6-7 h of the infusion. Plasma GH concentrations were determined by RIA. Saline-treated animals exhibited the typical pattern of spontaneous GH pulses. The frequency of GH pulses in animals infused with either dose of GRF was not different from that of the saline-infused rats. Likewise, trough GH concentrations were similar in all three treatment groups. However, peak GH concentrations in the rats receiving the 15-micrograms/h GRF infusion were remarkably higher than the concentrations observed in the other two groups, regardless of the duration of the infusion. This resulted in mean GH concentrations being significantly higher (p less than 0.01) in the 15-micrograms/h GRF-infused rats. These results demonstrate that pituitary episodic GH secretion continues even in the presence of a continuous GRF stimulation.

Growth hormone releasing factor infusion does not sustain elevated GH-levels in normal subjects.

To evaluate the dynamics of GH-secretion after infusion of growth hormone releasing factor, human pancreatic growth hormone releasing factor (hpGRF1-44) was infused over 2 and 5 h at a dosage of 100 micrograms hpGRF1-44/h into 11 healthy subjects. The infusion was started and terminated with a 50 micrograms hpGRF1-44 bolus injection. In 5 subjects 200 micrograms TRH was given 4 h after starting the infusion. In addition, 4 healthy subjects received 50 micrograms hpGRF1-44 bolus injection every 2 h. GRF, somatostatin, GH, Prl, and TSH were measured by radioimmunoassay. The initial 50 micrograms GRF bolus increased GH-levels in all 11 subjects with a maximum at 30 min (24.1 +/- 5.1 ng/ml +/- SE). However, though hpGRF1-44 was continuously infused and GFR-levels remained elevated, GH decreased to a minimum 270 min after start of infusion (2.6 +/- 0.6 ng/ml). The GH-response to the second bolus at the end of the infusion was lower compared to the first response (14.6 +/- 3.4 ng/ml after 2 h and 7.6 +/- 2.5 ng/ml after 5 h). TRH did not lead to a GH-increase during hpGRF1-44 infusion though Prl and TSH rose normally. The intermittent bolus injection of 50 micrograms hpGRF1-44 led to continuously decreasing GH-responses to the same GRF-dosage (I. bolus: 16.5 +/- 1.6 ng/ml; II. bolus: 4.2 +/- 0.8 ng/ml; III. bolus: 3.4 +/- 0.5 ng/ml). No change in somatostatin levels was observed. These findings show that GRF infusion or bolus injection in short intervals does not sustain elevated GH-levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Pituitary growth hormone response in rats during a 24-hour infusion of growth hormone-releasing factor.

The pituitary GH response during a 24-h iv infusion of GH-releasing factor (hpGRF-44; 15 micrograms/h) and to a subsequent bolus injection of hpGRF-44 (2 micrograms) was studied in conscious, freely moving male rats pretreated with antiserum against somatostatin. Within 2 h of the initiation of the hpGRF-44 infusion, plasma GH concentrations rose from 169 +/- 16 to 2465 +/- 307 (+/- SE) ng/ml. By 6 h, plasma GH concentrations began to fall. They decreased slowly and reached a nadir of 490 +/- 107 ng/ml by 12 h. Rats infused for 24 h with hpGRF-44 failed to respond to a 2-micrograms bolus injection (iv) of hpGRF-44, whereas rats infused for 24 h with saline responded with a normal increase in plasma GH. The pituitary GH content of rats treated with saline was significantly greater than that of rats treated with hpGRF-44. These results demonstrate that the capacity of the pituitary to respond to GRF can be exhausted after the chronic administration of hpGRF-44 and that this lack of response appears to be due, in part, to a depletion of pituitary stores of GH.

Plasma growth hormone secretion during constant growth hormone-releasing factor infusion.

Synthetic human pancreatic growth hormone-releasing factor (hpGRF-44) was infused intravenously at a constant rate of 2.5 micrograms/min for 180 minutes in 3 normal boys of short stature. Plasma GH levels reached a peak at 60-120 min with a mean value (+/- SEM) of 69.1 +/- 14.3 ng/ml, and then, declined gradually in spite of continuous hpGRF-44 infusion up to 180 minutes. Similarly, constant infusion of hpGRF-44 at a rate of 2.5 micrograms/min in 5 normal but short boys for 90 minutes, together with an iv bolus injection of hpGRF-44 (2 micrograms/kg) administered at 0 and 90 minutes, elicited a prompt rise in plasma GH 15-30 minutes after the first bolus but no significant elevation of GH was observed after the second bolus. In contrast, when two iv bolus injections of hpGRF-44 (2 micrograms/kg) were given in 4 normal boys with short stature at 0 and 90 minutes, respectively, significant elevation of plasma GH was found after each bolus. These results suggest that under constant infusion of GRF the pituitary experiences a down-regulation after the initial peak of GH response, possibly due to desensitization to GRF.

An ultrastructural and radioimmunoassay study of anterior pituitary somatotrophs following pituitary portal vessel infusion of growth hormone releasing factor.

The hypophysial portal vessels and anterior pituitary glands of adult male rats were surgically exposed, cannulated and infused for 1 min with saline, growth hormone-releasing factor (GH-RF), and dbcAMP. After cessation of infusion, anterior pituitary glands were collected at 1, 5, 15, 30 or 60 min for electron microscopic and ultrastructural cytochemical examination. Before and after cannulation of a portal vessel a 1-ml sample of blood was collected at 1, 5, 15, 30 or 60 min from the femoral vein for RIA of growth hormone. When viewed ultrastructurally, the initial response following the infusion of GH-RF into a portal vessel was one of granule release. Emiocytic activity was observed at all time intervals studied. This response was followed 30 min later by evidence of increased protein synthesis. Significant increases in plasma GH levels were present at 1, 5, and 15 min following infusion of GH-RF but not at 30 or 60 min. Preliminary analysis of the RIA data suggests that dbcAMP was significantly more potent than GH-RF in elevating radioimmunoassayable plasma GH levels. The results suggest that similar mechanisms of synthesis and release were involved.