Injections Of Growth Hormone-releasing Factor Research Articles

Effects of growth hormone-releasing factor on growth hormone response, growth and feed conversion efficiency in buffalo heifers ( Bubalus bubalis)

The aim of this study was to determine the benefits of growth hormone-releasing factor (GRF) on growth and feed conversion efficiency (FCE) in buffaloes. Twelve Murrah buffalo heifers ( Bubalus bubalis) of mean age 24.8 months and mean body weight 302.4 kg were divided into two groups (treatment and control) with six animals in each group. The buffaloes were given intravenous injections of bovine GRF (bGRF) at a dose rate of 10 μg/100 kg body weight or an equal volume of saline at 15-day intervals for a period of 9 months. Plasma growth hormone (GH) responses to bGRF challenge were measured in blood samples collected at 90-day intervals on days 1, 90, 180 and 270 and samples were taken at −60, −30, 0, +10, +20, +30, +60, +120 and +180 min relative to bGRF injection. Blood samples were also collected weekly by jugular venepuncture for the quantification of plasma GH. The average growth rate (AGR) and FCE of all animals were recorded at 15-day intervals. Plasma GH concentrations increased ( P = 0.001) steadily following bGRF challenge, peaking 10–20 min after challenge and declining to baseline by 180 min. In the treatment group, there were no significant differences ( P > 0.05) in either the peak heights of the GH response or the area under the curve (AUC) of the GH response after bGRF challenge on any of the four occasions of intensive bleeding. There were overall increases in plasma GH concentrations ( P < 0.01), AGR ( P < 0.01) and FCE ( P = 0.05) in the treatment group compared with the control animals. The study showed that GH responsiveness to administration of bGRF at 15-day intervals over 9 months of treatment remained unchanged in buffalo heifers. Exogenous bGRF treatment for a long period can therefore enhance GH release leading to higher growth rates and better feed conversion efficiency in buffalo heifers.

Mammary gland development of sows injected with growth hormone-releasing factor during gestation and(or) lactation

Twenty-four gilts received s.c. injections of saline or growth hormone-releasing factor (GRF) in late gestation and(or) lactation. Sows were sacrificed on day 30 of lactation and functional mammary glands were excised for chemical analyses. Weight of parenchymal (P = 0.004) and extra-parenchymal tissues (P = 0.002) were decreased with GRF injections during lactation. Parenchymal mass per milligram of DNA also decreased (P = 0.025) with GRF in lactation while parenchymal DNA concentration increased (P = 0.03). Exogenous GRF given to sows during lactation therefore decreased total parenchymal mass, increased cell density and decreased mammary cell size. Key words: Sow, mammary gland, growth hormone-releasing factor

Dynamics of secretory granules in somatotrophs of rats after stimulation with growth hormone-releasing factor: a stereological analysis.

The anterior pituitary tissue of male rats injected with growth hormone-releasing factor (GRF) was either processed for stereology at the light- and electron-microscopic levels, or homogenized for growth hormone (GH) assay 2-60 min after GRF injection. Secretory granules of somatotrophs became smaller but increased in numerical density 2 min after GRF injection. Their volume density began to increase at 5 min. The frequency of exocytosis of the granules was most prominent as early as 2 min after GRF injection and reduced thereafter. GH levels in the tissue were lowest at 2-5 min, and returned to the control value by 60 min. Serum GH levels were highest at 15 min; even at 60 min, this value was higher than in the controls. These findings suggest that secretory granules in somatotrophs are stimulated to divide by GRF, resulting in a decrease in size and an increase in number. The discrepancy between the earlier formation of new secretory granules and the later restoration of intracellular GH levels implies that GRF first stimulates the synthesis of constituents of granules other than GH, and only later the synthesis of GH, and that newly formed small secretory granules contain less GH. From the clearance rate of serum GH and the frequency of granule exocytosis, it can be estimated that about a half million granules are released to maintain 1 ng/ml of serum GH in rats.

Central effects of growth hormone-releasing hexapeptide (GHRP-6) on growth hormone release are inhibited by central somatostatin action

Growth hormone (GH) release is stimulated by a variety of synthetic secretagogues, of which growth hormone-releasing hexapeptide (GHRP-6) has been most thoroughly studied; it is thought to have actions at both pituitary and hypothalamic sites. To evaluate the central actions of this peptide, we have studied GH release in response to direct i.c.v. injections in anaesthetized guinea pigs. GHRP-6 (0.04-1 microgram) stimulated GH release > 10-fold 30-40 min after i.c.v. injection. The same GH response required > 20-fold more GHRP-6 when given by i.v. injection. GH release could also be elicited by a non-peptide GHRP analogue (L-692,585, 1 microgram i.c.v.), whereas a growth hormone-releasing factor (GRF) analogue (human GRF27Nle(1-29)NH2, 2 micrograms, i.c.v.) was ineffective. A long acting somatostatin analogue (Sandostatin, SMS 201-995, 10 micrograms i.c.v.) (SMS) given 20 min before 200 ng GHRP-6 blocked GH release. This was unlikely to be due to a direct effect of SMS leaking out to the pituitary, since central SMS injections did not affect basal GH release, nor did they block GH release in response to i.v. GRF injections. We conclude that the hypothalamus is a major target for GHRP-6 in vivo. Since the GH release induced by central GHRP-6 injections can be inhibited by a central action of somatostatin, and other data indicate that GHRP-6 activates GRF neurones, we suggest that somatostatin may block this activation via receptors known to be located on or near the GRF cells themselves. Somatostatin may therefore be a functional antagonist of GHRP-6 acting centrally, as well as at the pituitary gland.

Effects of growth hormone-releasing factors and cottonseed meal on hormones and metabolites in plasma from lambs fed lucerne chaff ad libitum

This study was part of an experiment on the effects of cottonseed meal (CSM) and growth hormone-releasing factor (GRF) on growth in lambs fed lucerne chaff. Forty-eight crossbred lambs were fed lucerne chaff ad libitum, alone or with a cottonseed meal supplement (CSM; 300 g/day). Eight lambs from each group were injected twice daily with recombinant or synthetic GRF (rGRF and sGRF respectively; 30 8g per kg body weight/day) or excipient only for 28 or 30 days. Jugular blood samples were obtained on days 0, 7, 14, 21 and 28. On day 29, blood samples were taken from selected lambs (n = 2/group) at 0, 20, 40, 60, 80, 100, 120, 160 and 240 min after injection. Supplementation of lucerne chaff with CSM generally increased glucose and urea concentrations in plasma, reflecting improved energy and protein status. However, concentrations of growth hormone, insulin-like growth factor-1 and insulin were unaffected by CSM, as were plasma proteins, triacylglycerols and non-esterified fatty acids. Injection of rGRF and sGRF stimulated secretion of growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin. Peak GH concentrations (20 min) following injection of GRF appeared to be higher in lambs fed CSM than in those receiving lucerne chaff alone. In contrast, maximal concentrations of IGF-1 were seen after 14 days of treatment. These changes were accompanied by increased plasma glucose, with no changes in triacylglycerols, non-esterified fatty acids and protein. Plasma urea was reduced by GRF, indicating that amino acids were diverted away from catabolism towards protein synthesis. These two sources of GRF were very similar in their endocrine and metabolic effects. This confirms similar observations regarding their effects on growth performance and carcass composition.

Constitutive growth hormone secretion in sheep after hypothalamopituitary disconnection and the direct in vivo pituitary effect of growth hormone releasing peptide 6.

The effect of hypothalamopituitary disconnection (HPD) on growth hormone (GH) secretion was studied in sheep. Plasma GH levels were measured in serial blood samples (10 min x 6-8 h) taken from 12 Romney wethers and 5 ewes which had undergone HPD 40-506 days earlier and from 4 wethers (10 min x 7 h) to serve as controls. Five wethers and 5 ewes were taken approximately 300 days after HPD and injected with vehicle or 10 micrograms/kg of the synthetic hexapeptide growth hormone-releasing peptide 6 (GHRP-6); GH responses were monitored. In a second series of sheep, 4 wethers and 6 HPD wethers were given saline, 0.5 micrograms/kg of synthetic growth hormone-releasing factor (GRF) or 5 micrograms/kg GHRP-6 and were blood-sampled to measure the plasma GH response. A further group of 4 HPD wethers and 3 control wethers were killed and the anterior pituitary glands collected for the quantification of GH and LH beta mRNA by Northern analysis. Three HPD wethers and 1 HPD ewe and 1 control ewe were killed and their brains were perfused; the hypothalami were sectioned and immunostained for the presence of GRF-containing fibres in the median eminence. Normal episodic GH secretion was abolished by HPD in both wethers and ewes but plasma values did not fall below the assay detection limit, indicating constitutive secretion. Northern blot analyses showed that the GH mRNA was detectable in HPD wethers at a lower (p < 0.05) level than in control animals but mRNA for LH beta was undetectable in the HPD wethers. Immunohistochemistry revealed GRF-positive staining in the median eminence of the controls but GRF-positive staining was not seen below the operation site in the median eminence of the HPD animals. In the first series, 3/5 wethers and 3/5 of the ewes responded to GHRP-6 challenge; the magnitude of the response was similar in both sexes. In the second series, responses to GRF were lower (48%) (p < 0.03) in HPD wethers than in control wethers, and responses to GHRP-6 were much lower (p < 0.01) than those to GRF in both controls and HPD wethers. These studies show that HPD removes GRF inputs to the pituitary gland and abolishes pulsatile GH secretion in most cases but constitutive non-pulsatile secretion continues. The HPD wether pituitary glands had lower GH mRNA levels than controls. Accordingly, HPD sheep were able to respond to a single injection of GRF although the response was half that seen in control animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Digestive enzyme development in newborn piglets born of sows immunized against somatostatin and/or receiving growth hormone-releasing factor during gestation.

Thirty-eight second parity sows were either immunized (IMM) against somatostatin (SRIF) and/or injected with growth hormone-releasing factor (GRF) during gestation. Treatment effects on pancreatic, gastric and duodenal development as well as on digestive enzyme activity of piglets at birth (before suckling) or at 24 h postpartum were investigated. Birth weights of piglets were similar across treatments (p > 0.1). Weight, DNA, RNA, total protein content and enzyme activity for all three organs increased between birth and 24 h postpartum (p < 0.01), except for pancreatic RNA and chymotrypsin which decreased (p < 0.01), and protein content of the pancreas which was unaltered (p > 0.1). Gastric RNA, pancreatic weight:DNA, RNA:DNA and amylase:DNA ratios were increased in 1-day-old piglets from SRIF-IMM sows (p < or = 0.05). GRF only had significant effects (p < 0.05) on the maltase:DNA ratio, which it decreased. Yet, there were tendencies (p < 0.1) for duodenal weight, DNA and total protein content to be increased in piglets from GRF-injected dams. It is therefore apparent that major developmental changes of the pancreas, stomach and duodenum of piglets take place during the first 24 h postpartum. Injections of GRF and/or immunization against SRIF during gestation in swine also have several effects on digestive enzyme activity of neonatal pigs. Yet, the physiological implications of these early changes are not clear at the present time.

Lactation performance of sows injected with growth hormone-releasing factor during gestation and(or) lactation.

Fifty-two Yorkshire x Landrace gilts were equally allotted to four treatments: 1) controls, saline injections (CTL); 2) injections of 12 mg of growth hormone-releasing factor (GRF) (1-29)NH2 thrice daily (0700, 1500, and 2300) from d 100 of gestation until parturition (GEST); 3) injections of GRF thrice daily from d 3 to 29 of lactation (LACT); and 4) injections of GRF thrice daily during gestation (d 100 to parturition) and lactation (d 3 to 29) (GEST-LACT). Within 48 h of birth, litters were standardized to 9 +/- 1 pigs. Weights of the pigs were recorded weekly from birth (less than 24 h) until weaning (d 30) and on d 42 and 56. Weights of gilts at mating, d 110 of gestation, 1 d postfarrowing, and at weaning also were recorded. On d 24 of lactation, milk yield was estimated by the weigh-suckle-weigh method, and a representative milk sample was obtained the next day. Jugular vein cannulas were inserted into six sows per treatment on d 26, and a 6-h blood profile (sampling every 20 min from 0600 to 1200) was obtained on d 29. Daily feed consumption of sows was recorded throughout the study. Weights of the pigs at any one time or survival until weaning were not affected by treatments (P greater than .1). Sows injected with GRF during GEST (P = .05) and(or) LACT (P less than .01) were lighter than CTL sows at weaning; in addition, sows treated during lactation had less backfat (P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of administration of growth hormone-releasing factor to sows during late gestation on growth hormone secretion, reproductive traits, and performance of progeny from birth to 100 kilograms live weight.

The effects of growth hormone-releasing factor (GHRF) injections to sows during late gestation were investigated in two experiments. In the first one, four treatments were applied to eight catheterized sows according to two 4 x 4 Latin squares: oral administration of 2 mg of pyridostigmine, a cholinesterase inhibitor, per kilogram of BW (PYR group); i.m. injection of 50 micrograms of GHRF/kg BW (GHRF group); a combination of the pyridostigmine and GHRF treatments (PYR+GHRF); or i.m. injection of glucose (control). Pyridostigmine slightly increased the plasma concentration of growth hormone (GH). Growth hormone responses to GHRF and PYR+GHRF treatments were similar, with significantly elevated GH concentrations from 5 to 240 min after GHRF injection. In the second experiment, 36 sows were allocated to two treatments at 102 d of gestation. Until farrowing, they were injected twice daily with 50 micrograms of GHRF/kg BW (GHRF group) or isotonic glucose (control). The DM, N, fat, and energy content of 24 pigs per group was determined at weaning at 22 d. Six pigs per litter had ad libitum access to feed until slaughter at 100 kg BW and their carcasses were evaluated. Treatment with GHRF increased pregnancy duration (114.8 vs 113.6 d, P less than .05), weight of pigs at 13 d (3.69 vs 3.54 kg, P less than .05) and at weaning (5.74 vs 5.48 kg, P less than .05), and improved pig survival (86 vs 71%, P less than .05). Lipid (on a DM basis) and energy contents of the pigs slaughtered at weaning were significantly higher in the GHRF group than in the control group (14.4 vs 12.5% and 2,178 vs 2,029 kcal/kg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of growth hormone-releasing factor and feed intake on energy metabolism in growing beef steers: net nutrient metabolism by portal-drained viscera and liver2

Effects of growth hormone-releasing factor (GRF) and intake on net nutrient metabolism by portal-drained viscera (PDV) and liver were measured in six growing Hereford x Angus steers fed a 75% concentrate diet at two intakes in a split-plot design with 4-wk saline or GRF injection periods within 8-wk intake periods. Daily rations were fed as 12 equal meals delivered every 2 h. Steers were injected s.c. for 21 d with either saline or 10 micrograms/kg of (1-29)NH2 human GRF at 12-h intervals. Six hourly measurements of net nutrient flux (venous-arterial concentration different [VA] x blood flow) across PDV and liver were obtained 8 to 10 d after injections began. Energy and N balances were measured using respiration calorimetry during the last week of injections. Greater intake increased blood flow (P less than .01) and net visceral release or removal of most nutrients (P less than .10). Exceptions included a decrease (P less than .10) in net PDV glucose release with greater intake in saline-treated steers and a decrease (P less than .01) in net liver removal of lactate with greater intake. Treatment of steers with GRF decreased net liver removal of alpha-amino N (AAN; P less than .05) and ammonia N (NH3N; P less than .10) and release of urea N (UN; P less than .05), increased liver release of glutamate (P less than .05), and decreased net PDV release of NH3 N (P less than .10). Decreased liver extraction ratio for AAN in GRF-treated steers (P less than .01) implies a direct effect of GRF treatment on liver metabolism separate from changes in liver AAN supply. Proportions of body N retention not accounted for by net total splanchnic AAN release increased with GRF treatment. This suggests a change in peripheral utilization of dietary AAN supply or an increase in total splanchnic N retention.

Effect of FSH-P priming on superovulatory response in buffalo (Bubalus bubalis)

The aim of this study was to determine the benefits of growth hormone-releasing factor (GRF) on growth and feed conversion efficiency (FCE) in buffaloes. Twelve Murrah buffalo heifers (Bubalus bubalis) of mean age 24.8 months and mean body weight 302.4 kg were divided into two groups (treatment and control) with six animals in each group. The buffaloes were given intravenous injections of bovine GRF (bGRF) at a dose rate of 10 μg/100 kg body weight or an equal volume of saline at 15-day intervals for a period of 9 months. Plasma growth hormone (GH) responses to bGRF challenge were measured in blood samples collected at 90-day intervals on days 1, 90, 180 and 270 and samples were taken at −60, −30, 0, +10, +20, +30, +60, +120 and +180 min relative to bGRF injection. Blood samples were also collected weekly by jugular venepuncture for the quantification of plasma GH. The average growth rate (AGR) and FCE of all animals were recorded at 15-day intervals.Plasma GH concentrations increased (P = 0.001) steadily following bGRF challenge, peaking 10–20 min after challenge and declining to baseline by 180 min. In the treatment group, there were no significant differences (P > 0.05) in either the peak heights of the GH response or the area under the curve (AUC) of the GH response after bGRF challenge on any of the four occasions of intensive bleeding. There were overall increases in plasma GH concentrations (P < 0.01), AGR (P < 0.01) and FCE (P = 0.05) in the treatment group compared with the control animals. The study showed that GH responsiveness to administration of bGRF at 15-day intervals over 9 months of treatment remained unchanged in buffalo heifers. Exogenous bGRF treatment for a long period can therefore enhance GH release leading to higher growth rates and better feed conversion efficiency in buffalo heifers.

Growth hormone response to acute growth hormone releasing hormone administration in uraemic patients on haemodialysis.

To examine the response of growth hormone (GH) to growth hormone releasing factor (GHRF) in patients on haemodialysis, we performed the acute GHRF test (50 micrograms administered intravenously as a bolus) in 10 uraemic male patients on haemodialysis and eight normal controls. Each patient was tested before and after a haemodialysis session (at 08.30 and 12.30). Controls were tested on the same time schedule. At 08.30, patients had significantly greater basal and peak GH values (2.5 +/- 0.6 and 27.8 +/- 5.5 micrograms/l) than controls (0.68 +/- and 11.5 +/- 4 micrograms/l). After the haemodialysis session, basal and peak values declined significantly (P less than 0.01) in the uraemic group (0.5 +/- 0.03 and 3.1 +/- 1.1 micrograms/l), whereas the controls did not show such a change in the 12.30 test. Basal and intratest glycaemic values were comparable both before and after haemodialysis. After dialysis test results did not change either with the use of glucose-free dialysate or with bicarbonate buffer. Uraemic patients display a greater GH response to GHRF injection than normal subjects, and this response decreases after haemodialysis. The degree of reduction has no relationship with either glycaemia or the dialysate buffer. We suggest that other GH secretion regulating factors are altered by the haemodialysis procedure.

Carcass composition and resistance to fasting in neonatal piglets born of sows immunized against somatostatin and/or receiving growth hormone-releasing factor injections during gestation.

Thirty-eight gestating sows were either immunized against somatostatin (SRIF) and/or injected with growth hormone-releasing factor (GRF). Treatment effects on carcass composition and resistance of newborn piglets to a 60-hour fast were investigated. Protein content of carcasses at birth was increased in piglets of sows receiving GRF or immunized against SRIF, however, when sows received both treatments there was a reduction in carcass protein content (p = 0.01). Other carcass components were unaltered by treatments, and none of the treatments affected metabolic or endocrine profiles of piglets at birth. Concentrations of GH, IGF-I (p less than 0.01), glucagon and cortisol (p less than 0.05) increased linearly with duration of fast, whereas glucose values decreased. Resistance to fasting was unaltered in piglets from any treatment thereby suggesting that exogenous GRF and/or SRIF immunization of sows during gestation are unlikely to improve survival of newborn piglets.

Effect of hypothalamic administration of growth hormone-releasing factor (GRF) on feeding behavior in rats

To examine the role and working site of growth hormone-releasing factor (GRF) in feeding behavior, we first tested the effect of the intracerebroventricular (i.c.v.) injection of GRF on food intake after 24 h of food deprivation. Cumulative food intake was measured 1, 3 and 6 h after injection. A lower dose of GRF stimulated food intake in a dose dependent manner (3h; GRF100pmol8.64 ± 1.06g vs saline5.50 ± 0.60g, P < 0.05), while a higher dose (1 nmol, 500 pmol) suppressed food intake (3h; GRF1mol2.65 ± 0.70g vssaline5.50 ± 0.60g, P < 0.01). Second, the effect of i.c.v. injection of 100 pmol of GRF on peripheral metabolites was examined. The subsequent levels of plasma insulin, glucagon, glucose and non-esterified fatty acid showed no significant difference from those of saline administration. Third, the effect of microinjection of GRF (5 pmol) into several hypothalamic areas on food intake was examined. Injection into the ventromedial hypothalamic nucleus (VMN) stimulated food intake (3h;GRF5pmol10.32 ± 1.04g vs saline6.92 ± 0.32g, P < 0.05), but no significant effect was observed following injection either into the lateral hypothalamic area (LHA), paraventricular nucleus (PVN) or medial preoptic area (MPOA). Finally, we tested the stimulatory effect of GRF on food intake in bilateral VMN lesioned rats. I.c.v. injection in these animals had no more significant effect on food intake than did saline injection in VMN lesioned rats (3h;GRF100pmol6.27 ±0.87g vs saline5.34 ± 0.44g). These results suggest that administration of a low dose of GRF centrally enhances feeding behavior and that the VMN is one of the working sites of this effect.

Effects of active immunization against somatostatin (SRIF) and/or injections of growth hormone-releasing factor (GRF) during gestation on hormonal and metabolic profiles in sows

The hormonal responses of gestating sows to immunization against somatostatin conjugated to bovine serum albumin (SRIF-IMM) and/or injections of growth hormone-releasing factor (GRF) were studied with thirty-eight second parity sows. Immunization against bovine serum albumin (BSA-IMM) was used as control. First immunizations were done on day 30 and boosters were given on days 44, 58, 72, 86 and 100 of gestation. Injections of GRF (9 mg of GRF (1–29)NH 2 per injection) or saline were given at 0800, 1400 and 2000 hr daily from day 90 of gestation until parturition. Mean body weights of sows at 85 and 110 d of gestation were 196.3 and 210.5 kg, respectively (SE = 0.8). Jugular blood samples were collected from 0740 hr to 1100 hr at 20 min intervals on days 90, 101 and 112 of gestation. On day 112, additional samples were collected from 1340 hr to 1700 hr and from 2140 hr to 2300 hr. At 112 d of gestation, antibody titers against SRIF (% binding, 1:150 dilution) were higher (P<0.01) for SRIF-IMM (13.5%) vs BSA-IMM (0.95%) sows. There was no effect of SRIF-IMM nor was there a GRF by SRIF-IMM interaction on any variable measured (P>0.05). Injections of GRF increased (P<0.01) the area under the curve (AUC) for growth hormone (GH; 305 vs 1623 ng/min/ml). The increase was greater as days of injection increased (P<0.05). Administration of GRF did not affect prolactin (Prl) AUC (P>0.05). There was no effect of time of injection on GH or Prl AUC (P>0.05). There was no effect of treatments on free fatty acids (FFA), glucose or insulin (P>0.05) but insulin-like growth factor I (IGF-I) concentrations increased in GRF-treated sows (P<0.01; 66 vs 101 ng/ml). Concentrations of FFA and IGF-I increased (P<0.01) as gestation advanced. Treatment with GRF increased weight gain of sows during late lactation (P<0.01). In conclusion, GH AUC was increased by GRF injections but not by SRIF-IMM in gestating sows. Concentrations of FFA, glucose and insulin were not altered by either treatment, but those of IGF-I were increased by GRF.

Growth hormone parameters at four ages in intact and castrated male and female cattle

Plasma Growth hormone (GH) profiles, secretion rates (SR), metabolic clearance rates (MCR) of intravenously infused GH, and response to 0.0165, 0.067, and 0.267 μg of growth hormone-releasing factor (GHRF)/kg body weight (bwt) were studied in intact and castrated male and female cattle (4 of each) at 5, 8, 12, and 15 mo of age. As cattle aged, overall GH levels in the plasma decreased (P<.01), GH baseline concentrations declined (P<.05), SR decreased (P<.01), half-life of GH decreased (P<.01), and the GH response to intravenous injections of GHRF declined (P<.05). Bulls had elevated overall and baseline GH concentrations (P<.05), greater amplitude and number of GH secretory periods (P<.01), and greater SR (P<.05) than steers, heifers, or ovariectomized heifers. Males had more frequent GH spikes and secretory periods of higher amplitudes, greater SR, and greater GH responses to 0.0165 μg GHRF/kg bwt (P<.05) than females. Castration had no impact on the GH status of heifers. It is suggested that testosterone or its metabolites enhanced GH secretion in bulls.

Central somatostatin: a re-examination of its effects on feeding

Previous investigations of centrally administered somatostasin (SRIF) have tended to employ pharmacological (nmol and greater) doses of the peptide. Under this protocol contradictory findings of feeding effects have been reported. There is evidence that the use of physiological doses can induce a completely distinct response from that obtained with pharmacological doses. In order to discern whether physiological doses of centrally administered somatostatin have any effect on feeding. SRIF in doses ranging from 0.4 pmol to 3 nmol were administered into the lateral ventricles of rats. Low pmol doses (0.4–40) administered during the light photoperiod increased 1 h feeding whereas 3 nmol decreased 1 h feeding. None of the doses tested during the dark photoperiod significantly altered 1 h food intake. Similarly, no significant change in 24-h food intake was observed following injections of any of the doses tested, whether in the light or dark. A dose of SRIF that increased feeding (1 pmol) did not significantly alter 1 h water intake when applied centrally in the light nor did it alter spontaneous locomotor activity. Furthermore, when applied peripherally it did not change 1 h food intake. These studies suggest that SRIF may work centrally to regulate food intake. A similarity exists between SRIF's feeding effects and the feeding effects we have previously described following central injections of growth hormone-releasing factor (GRF), both in terms of dose-response and photosensitivity. This suggests that these 2 peptides may act via a common mechanism to regulate food consumption; possibly in co-ordination with their regulation of growth hormone release. The possibility that such feeding regulation occurs as part of a short intrahypothalamic feedback loop is discussed.

Characterization of feeding behavior induced by central injection of GRF

The behavior resulting from injection of rat hypothalamic growth hormone-releasing factor (GRF) (0, 0.01, 0.1, 1.0 pmol) into the suprachiasmatic nucleus-medial preoptic area (SCN/MPOA) or the paraventricular nucleus (PVN) of the hypothalamus was examined. After injections of GRF, feeding and other behavioral responses of male Wistar rats were observed for 90 min. In the SCN/MPOA, GRF dose dependently increased food intake, increasing mean meal length at 0.1 pmol and increasing rate of eating with no effect on meal length at 1.0 pmol. Other behavioral measures were unaffected by GRF. There was no effect after injections into the PVN. These data are taken as confirmation that the SCN/MPOA region of the hypothalamus is important for the central stimulatory effects of GRF on feeding. The possibility that the PVN is involved in the expression of feeding derived from intra-SCN/MPOA GRF injections is discussed.

The Antagonism of Glucocorticoid Inhibition of Wound Healing in Rats by Growth Hormone-Releasing Factor

Daily therapeutic injections of cortisone to rats will cause weight loss and impaired wound healing. Weight loss is attributed to the catabolic effect of steroid, whereas impaired healing is associated with reductions in fibroplasia and connective tissue deposition. As the major structural protein component of connective tissue is collagen, its absence is responsible for the retarded gain in wound breaking strength. Cortisone also blocks wound closure by inhibiting wound contraction. An anabolic agent such as growth hormone may antagonize the effect of cortisone on the wound healing process. Endogenous GH can be released from the pituitary by exogenous injections of growth hormone-releasing factor (GRF). Two synthetic GRF peptides, a natural 44-amino acid peptide of the human GRF sequence, GRF-44, and an N-terminally substituted analog 29 residues, GRF-29A, were studied. Each was given twice daily with a single daily injection of cortisone for a 7-day period. Concurrent administration of GRF-44 or GRF-29A and cortisone to rats had no effect on restored body weight loss or inhibited wound contraction. While GRF-44 restored collagen deposition and caused restored wound breaking strength, GRF-29A was ineffective in restoring either. GRF-44, a synthetic peptide that stimulates pituitary release of growth hormone, antagonized some of the inhibiting effect of steroid on wound repair by promoting fibroplasia and collagen deposition.

Insulin-like growth factor-I concentration in Holstein female cattle: variations with age, stage of lactation and growth hormone-releasing factor administration

Plasma insulin-like growth factor-I (IGF-I) concentrations were monitored in Holstein females through different periods of their growth, lactation and after acute or chronic growth hormone-releasing factor (GRF) administration. Plasma samples were radioimmunoassayed using a human IGF-I antibody after a 24 hr incubation in a HC1(.1N)-glycine(.2M) buffer (pH 2). In a first study, IGF-I concentrations were measured in Holstein females of different ages and(or) stages of lactation (n = 6 per group). The IGF-I concentrations in newborn calves (102.0 ± 11.3 ng/ml) markedly decreased (P<.01) in 1 mo old animals (50.2 ± 7.1 ng/ml), then increased (P<.01) to 137.0 ± 5.1 and 137.4 ± 11.0 ng/ml in 6 and 10 mo old heifers, respectively. In dairy cows, IGF-I concentrations were low 24 hr post-partum (44.7 ± 7.6 ng/ml) and then increased (P<.05) to remain stable throughout lactation (91.3 ± 4.9, 92.8 ± 12.9, 96.1 ± 7.6, 90.7 ± 8.8 ng/ml at 2, 3, 6 and 9 mo of lactation, respectively). There was a further increase (P<.05) to 113.7 ± 3.1 ng/ml during the dry period. In a second trial, blood samples were collected from lactating dairy cows every 2 hr for 24 hr following a sc injection of saline (n = 4) or human (h) GRF (1–29)NH 2 (10 μg/kg BW, n = 4). The IGF-I peak concentration was reached on average 10 hr after the GRF injection and was higher (P<.01) in treated cows than in control cows (135.4 vs 86.9 ± 16.2 ng/ml). In the last trial, daily sc injections of 10 μg of hGRF(1–29)NH 2 per kg BW to dairy cows (252 days of lactation) for 57 days, which increased milk production by 14% (2 kg/day), also increased (P<.01) IGF-I concentration: 127.1 ± 5.3 and 118.0 ± 1.6 vs 90.7 ± 4.7 and 96.0 ± 5.0 ng/ml on days 29 and 57 of treatment for treated (n = 9) and control (n = 8) cows, respectively. Thus, the IGF-I concentration in dairy cattle varies with age and stage of lactation, and is increased by GRF administration in lactating dairy cows.