A Moloney MLV-rat somatotropin fusion gene produces biologically active somatotropin in a transgenic pig.

Expression of a Moloney murine leukemia virus (MLV) rat somatotropin fusion gene was examined in a transgenic pig. The fusion gene was integrated in a single site within the genome in a tandem array with approximately eight copies per cell. The integrated in a single site within the genome in a tandem array with approximately eight copies per cell. The integrated MLV-rat somatotropin fusion gene produced high levels of circulating rat somatotropin and resulted in an elevation in the circulating levels of insulin-like growth factor I. Although there was no increase in the rate of growth of the transgenic animal during the rapid growth phase, several phenotypic changes were evident. Skeletal growth was markedly increased and fat deposition was reduced throughout the animal. Blood glucose levels were elevated without ketosis. Northern blot analyses of rat somatotropin RNA revealed that expression of the fusion gene was highest in the spleen, lung, intestine, lymph nodes, and bone marrow. These results show that the MLV promoter can be used to express high levels of biologically active rat somatotropin in transgenic swine.

Intracerebroventricular melanin-concentrating hormone stimulates food intake in sheep.

Melanin-concentrating hormone (MCH) stimulates feeding when injected intracerebroventricularly (ICV) in rats. At present it is not clear whether the function of MCH is similar in ruminants, which are species with a continuous delivery of nutrients. Therefore the current investigation sought to determine the role of MCH in sheep. In the first experiment, six, castrate male sheep were satiated and received one of four treatments [saline, 0.1, or 1.0 nmol/kg MCH, and NPY (0.1 nmol/kg)] injected ICV over 30s, then infused ICV for 6 h ( approximately 500 microl/h). Food intake was measured for 2 h before and at 2, 4, 6, 8, 12 and 24 h. In this experiment, feed intake was increased (P

Obesity and dehydroepiandrosterone/dehydroepiandrosterone sulfate relationships in lean, obese, and meat-type cross-bred boars: responses to porcine growth hormone.

As so many variables can affect obesity (age, genetics, health status), new directions, other than reducing or altering diet, are being pursued in controlling obesity in our society. Both dehydroepiandrosterone (DHEA) and GH have reported antiobesity effects; thus, the possible interaction of these hormones was investigated in genetically lean, obese, and meat-type cross-bred male pigs (boars) administered implants that released 0, 2, or 4 mg/day recombinant porcine GH (pGH) for 42 days. Subcutaneous fat was determined by measurement of back fat depth at 2-week intervals, and blood samples were obtained 0, 7, 14, 28, and 42 days post-implant. The weight of perinephrenic fat, an index of abdominal fat, was obtained at death. The obese line had higher DHEA/DHEA sulfate (DHEA-SO4) serum concentrations than the lean and cross-bred boars. Treatment with pGH reduced sc and perinephrenic fat in all lines at both doses (P < 0.01). There was no relationship between day 42 concentrations of DHEA/DHEA-SO4 and indexes of obesity. Concentrations of DHEA/DHEA-SO4 were decreased by pGH treatment (P < 0.01) by days 7-14 in all genetic lines. Concentrations of insulin-like growth factor I, insulin-like growth factor II, and insulin were increased with pGH treatment in all lines (P < 0.01). The a priori hypothesis that increases in these peptides would stimulate gonadal steroidal synthesis (as demonstrated in vitro) and result in elevated DHEA/DHEA-SO4 concentrations and reduced obesity was not supported by pGH-induced decreases in DHEA/DHEA-SO4. Insulin concentrations were elevated 7-14 days postimplant in all lines (P < 0.01), then declined in the later stages of the trial. Insulin concentrations and DHEA/DHEA-SO4 concentrations were inversely related (r = -0.59; P < 0.05); this may indicate that with elevated insulin levels, DHEA/DHEA-SO4 is decreased and has a limited opportunity to affect obesity. Although the administration of DHEA may reduce obesity, the lipolytic action of pGH does not appear to be through increased circulating concentrations of DHEA/DHEA-SO4.

Endocrine and metabolite responses to porcine growth hormone administered by sustained release implant for different lengths of time in male pigs.

The effects of long term administration of GH on serum concentrations of hormones and metabolites was investigated in intact and castrate male swine. At 10 weeks of age, male swine were assigned to six treatments (n = 10/group): nonimplanted intact and castrate males; intact males implanted for 6 weeks, from 22-28 weeks of age; intact males implanted for 12 weeks, from 16-28 weeks of age; and intact and castrate males implanted for 18 weeks, from 10-28 weeks of age. Recombinant porcine GH was administered with sustained release implants designed to deliver a dose of 4 mg/day for 6 weeks. Throughout the study, blood samples were collected, and serum was harvested to quantitate circulating concentrations of glucose, urea nitrogen, GH, insulin, insulin-like growth factor I (IGF-I), IGF-II, and PRL. The pattern of administered GH in the serum suggests that the presence of testes and prior treatment with GH influence GH clearance. Somatotropin treatment elevated serum concentrations of GH and increased serum levels of glucose, insulin, IGF-I, and IGF-II in both intact and castrate animals. However, during the prepubertal period of 10-16 weeks, GH-treated intact males were resistant to the diabetogenic actions of GH, whereas significantly increased serum levels of glucose and insulin occurred in GH-treated castrates during this period. Changes in serum levels of IGF-I throughout the study and in insulin after the first 6 weeks followed the pattern of circulating GH concentrations in the treated animals. Serum concentrations of IGF-II were increased after GH administration, but, in contrast to the IGF-I response, IGF-II levels remained elevated as GH concentrations waned in the latter portion of the implant period. The maintenance of higher serum levels of IGF-II may be less dependent upon GH than are insulin and IGF-I. Administration of GH to intact males is more efficacious in altering metabolites and hormones, with the exception of IGF-I, during the peripubertal and postpubertal periods than during the prepubertal period.

Expression of insulin-like growth factor-I during chicken development.

We have investigated the expression of insulin-like growth factor-I (IGF-I) during ontogeny in the chick. IGF-I mRNA was first detectable in whole embryos on day 6, while serum IGF-I could be measured on day 9, the earliest time point examined. Serum IGF-I values rose 10-fold from about 3 ng/ml on day 10 to a prehatch peak of 30-35 ng/ml during days 15-17, and then declined to about 10 ng/ml at the time of hatching. On days 17 and 20 of incubation, IGF-I mRNA was detected in eye, skeletal muscle, and brain, but could not be found in liver or heart until after hatching. During the posthatch period, serum IGF-I rose from 10 ng/ml in the first week to 35-40 ng/ml during weeks 3-6, and liver IGF-I mRNA increased nearly 5-fold from weeks 1-7. The increases observed during weeks 1-3 correlated with a posthatch rise in serum GH from 21 to 37 ng/ml, although GH levels declined over the subsequent 4 weeks without an appreciable change in serum IGF-I values. By contrast, before embryonic day 12 no GH could be detected in the circulation, while IGF-I was 19 ng/ml on day 11. These observations suggest that there is both GH-dependent and GH-independent regulation of IGF-I gene expression in the chick, as has been found in mammals, and support the idea that IGF-I plays a role in chicken embryonic development.

The effects of thyroxine on serum and tissue concentrations of insulin-like growth factors (IGF-I and -II) and IGF-binding proteins in the fetal pig.

We have extensively studied the effect of hypophysectomy on the growth and development of tissues in the fetal pig. However, little is known about the effect of hypophysectomy on tissue levels of insulin-like growth factors I and II (IGF-I and -II) and how these growth factors are affected by T4 replacement. Fetal pigs were hypophysectomized (Hypox) at 70 days of gestation, and pellets containing 15 mg T4 were implanted into the lateral musculature of the hind limb at either 70 or 90 days of gestation. Fetuses were removed at either 90 or 105 days of gestation, respectively. Control (non-Hypox), Hypox, and T4 (Hypox-T4) fetal weights were similar at 90 days, but Hypox-T4 weighted less than control and Hypox fetuses at 105 days. Hypophysectomy decreased levels of serum T4, LH, cortisol, and IGF-I (105 days) when compared with controls. Heart and liver (105 days and 90 days) and fat, muscle, and kidney (90 days) IGF-I levels were lower in Hypox fetuses when compared with controls. Hypophysectomy decreased concentrations of IGF-II in only 105-day fetal kidneys. Hypophysectomy decreased serum levels of IGF binding protein 1 (IGFBP-1) (90 days) and IGFBP-2 (105 days) and increased IGFBP-4 (105 days) in comparison with control. T4 treatment of Hypox fetuses increased serum concentrations of T4 and IGF-I over Hypox levels at both 90 and 105 days gestation. Cortisol levels remained decreased in the T4-treated fetuses. Levels of IGF-I in the heart (90 and 105 days) and liver (90 days) of Hypox fetuses were increased by T4 treatment. T4 did not effect tissue IGF-II levels when compared with Hypox. T4 increased serum IGFBP-1, -2, and -4 levels over Hypox values. We suggest that T4 enhances production of IGF-I (as opposed to IGF-II), which in turn mediates some of T4's capability to enhance tissue development in the fetal pig.

Alterations in the growth hormone/insulin-like growth factor I pathways in feline GM1 gangliosidosis.

Cats affected with feline GM1 gangliosidosis, an autosomal, recessively inherited, lysosomal enzymopathy, have progressive neurological dysfunction, premature thymic involution, stunted growth, and premature death. Although increased membrane GM1 gangliosides can result in increased apoptosis of thymocytes, there is not a direct correlation between thymocyte surface GM1 and thymic apoptosis in vivo, suggesting that other factors may be important to the pathogenesis of thymic involution in affected cats. Because GH and insulin-like growth factor I (IGF-I) are important hormonal peptides supporting thymic function and affecting growth throughout the body, particularly in the prepubescent period, several components of the GH/IGF-I pathway were compared in GM1 mutant and normal age-matched cats. GM1 mutant cat serum IGF-I concentrations were reduced significantly compared with those in normal cats by 150 days of age, and GM1 mutant cats had no peripubertal increase in serum IGF-I. Additionally, IGF-binding protein-3 was reduced, and IGF-binding protein-2 was elevated significantly in GM1 mutant cats more than 200 days of age. Liver IGF-I messenger RNA and pituitary GH messenger RNA both were reduced significantly in GM1 mutant cats. After stimulation by exogenous recombinant canine GH, serum IGF-I levels increased significantly in GM1 mutant cats, indicating that GH/IGF-I signaling pathways within the liver remain intact and suggesting that alterations are external to the liver.

Stimulation of body weight gain of the mature female rat by bovine GH and bovine placental lactogen.

Mature female rats (200 g) were treated for 10 days with either recombinant bovine GH (bGH) or recombinant bovine placental lactogen (bPL) to compare the somatogenic responses elicited by these hormones. The treatments were administered by daily s.c. injection at four dose levels (0.19, 0.56, 1.67 and 5.0 mg/day). Both bGH and bPL stimulated significant increases in weight gain, but the slopes of the dose-response curves were different (P less than 0.05). Bovine PL was more potent than bGH (P less than 0.01) at the lowest dose, although there were no differences between treatment groups at the three higher doses. Feed consumption was stimulated more by bPL than bGH at all doses (P less than 0.001). The concentration of insulin-like growth factor-I (IGF-I) in blood plasma was increased by bGH in a dose-responsive manner and was higher than control at doses of 1.67 and 5 mg/day (P less than 0.05). Low doses of bPL stimulated increases in IGF-I similar to those with bGH. At the highest dose of bPL, however, there was no concomitant increase in plasma IGF-I. Nevertheless, the growth rate of the animals in this group matched that of the group given the highest dose of bGH. Receptor binding studies indicated that bPL bound to both GH and prolactin receptors. This is consistent with the growth data which suggests that bPL stimulated weight gain through a somatogenic mechanism as well as by another route, possibly mediated by lactogenic receptors.

Effect of growth hormone treatment on the distribution of insulin-like growth factor-I between plasma and lymph of lactating sheep.

Plasma and mammary efferent lymph concentrations of insulin-like growth factor I (IGF-I) were determined in lactating ewes before and after treatment with GH (10 mg/day) for 3 days. The lymph:plasma ratio of IGF-I increased from 0.34 to 0.47 after GH treatment when the IGF-I content of plasma increased by 19.4 nmol/l (from 32.1 nmol/l) and lymph by 13.7 nmol/l (from 10.7 nmol/l). This increase in the relative content of IGF-I in lymph was associated with increased lymph content of IGF-I in a lower molecular mass pool (nominally 50 kDa) derived by size exclusion chromatography. GH treatment increased the total binding capacity for IGF-I in both high (150 kDa) and low (50 kDa) molecular mass pools of plasma and the 150 kDa pool in lymph but there was a proportionally greater increase in 50 kDa total binding in lymph relative to plasma. Further, GH treatment increased the 'saturation' of the 50 kDa binding proteins but decreased the 'saturation' of the 150 kDa fraction, in both plasma and lymph. Ligand blot analysis of IGF-binding proteins (IGFBPs) in plasma and lymph showed that GH treatment of lactating sheep increased IGFBP-3 and decreased IGFBP-2 in plasma and lymph. Radioimmunoassay of IGFBP-2 showed that while GH treatment reduced the plasma content of IGFBP-2 by about half, the lymph:plasma ratio was increased from 0.68 to 0.87. GH treatment of lactating ewes not only increased the IGF-I content of plasma but increased the apparent efficiency of transfer of IGF-I across capillary endothelium to mammary efferent lymph.

Serum half-life and in-vivo actions of recombinant bovine placental lactogen in the dairy cow.

The clearance rate of recombinant bovine placental lactogen (rbPL) from the blood serum of four lactating dairy cows was measured using a specific radioimmunoassay. Two animals were non-pregnant, while the other two were at approximately 120 days of gestation. The rbPL was administered as an i.v. bolus injection (4 mg total) via an indwelling jugular catheter. Blood samples were taken periodically for 180 min and assayed for rbPL. Analysis of the clearance curves for the bolus injection suggested a single-compartment model and a serum half-life of 7.25 min. In a second experiment with the same animals, following cessation of lactation, rbPL or bovine GH (bGH) were administered by s.c. injection (50 mg/day) for 5 consecutive days. Blood samples were taken twice per day during the treatment period and a 3-day pretreatment period. Samples were analysed for glucose, blood urea nitrogen (BUN), non-esterified fatty acids (NEFA), creatinine, insulin, insulin-like growth factor-I (IGF-I) and IGF-II, tri-iodothyronine (T3), progesterone and IGF-binding protein-2 (IGFBP-2) to determine whether rbPL mediates similar metabolic effects to those of bGH. Administration of bGH stimulated an increase in NEFA, glucose, T3 and insulin, whereas none of these variables was affected by rbPL. The plasma concentrations of IGF-I and IGF-II were both increased by treatment with rbPL but, to a lesser extent than occurred with bGH. Interestingly, BUN and IGFBP-2 concentrations were reduced equally by bGH and rbPL. These results suggest that rbPL does not necessarily act as a GH agonist but, rather, may have distinct effects on intermediary metabolism that could be mediated through another specific receptor.

Stimulation of somatotropin secretion following peripheral administration of the tripeptide, syndyphalin 33 in sheep, pigs and rats.

In the present study, a simple tripeptide alkylamine, syndyphalin 33 (SD33, Tyr-DMet (O)-Gly-methylphenethylamide) was shown to stimulate somatotropin (GH) secretion in sheep, hogs and rats following peripheral administration. Intravenous (i.v.) administration of SD33 at doses of 0.05, 0.1 and 0.2 mumol/kg stimulated a significant increase in circulating GH levels in sheep within 5 minutes post-injection. This response was not attenuated following repeated i.v. injections of SD33 (0.05 /mmol/kg) administered at 2 hour intervals. In addition, plasma GH levels were significantly stimulated following either subcutaneous (s.c.) or oral administration of SD33 in hogs and rats. Subcutaneous administration of SD33 at doses of 0.5, 1.0 and 2.0 mumol/kg stimulated a significant increase in plasma GH concentrations within 30 minutes of injection in both species. Oral administration of SD33 at 1.0, 10 or 100 mumol/kg in rats resulted in a significant elevation in plasma GH levels which peaked at 30 minutes post-gavage. In the pig, circulating GH levels were significantly increased within 30 minutes post-ingestion and remained elevated for at least 2 hours at the 2.0 mumol/kg dose level. The ability of naloxone to block SD33-stimulated GH secretion suggests that this peptide acts via mu opiate receptors.

Changes in insulin, glucose and GH concentrations in fed chickens.

The concentrations of insulin, glucose and growth hormone were examined in chickens during the fed and fasted states. In broiler chickens between 5 and 7 weeks of age, blood samples were drawn at intervals which reflected fed (-4 hr), fasted (+0 min) and post meal states (+15 min, immediately after a 15 min meal (and +30 min). Plasma was assayed using a chicken insulin standard in a heterologous RIA. Overall insulin averages, reflecting averaged values for 10 birds/day and 5 replications revealed a decrease with fasting and an increase post-meal. Insulin levels returned to pre-fasted concentrations within 15 min of meal termination. Changes in glucose concentrations correlated with those of insulin with the exception of the +30 min period. When insulin levels were observed in chickens where no food was consumed, insulin levels at +0 and +15 min were not different. No difference in GH concentration occurred at -4 hr, +0 or +15 min but the +30 min value increased (p less than 0.05).

Effect of CCK antibodies on food intake and weight gain in Zucker rats.

While exogenous administration of cholecystokinin (CCK) decreases food intake in many species, it has not been demonstrated conclusively that CCK is necessary for satiety to occur. In these experiments the role of CCK in eliciting satiety was further investigated by using endogenously produced and exogenously administered antibodies to CCK which were hypothesized to sequester circulating CCK. In the first experiment Zucker obese (n = 12, 192 +/- 16 g) and lean (n = 12, 152 +/- 11 g) male rats were administered CCK-8 conjugated to bovine serum albumin or bovine serum albumin by subcutaneous administration in Freund's adjuvant. Average percent binding of 125I-gastrin-17 by serum taken 4, 8 and 12 weeks after treatment initiation was increased (19.9 vs. 2.1, p less than 0.001) in rats treated with CCK conjugate than controls, and the increase was greater in lean (27.5 vs. 1.9) than in obese (12.2 vs. 2.2, p less than 0.001) rats. In lean, but not obese rats, average daily food intake and weight gain were increased (9 and 17% p less than 0.04 and p less than 0.02 respectively) in rats with CCK-AB compared with rats with no CCK-AB during the three months. Development of CCK-AB did not affect food intake response to exogenously administered CCK-8 or pancreas weight relative to body weight. In Experiment 2 increased food intakes of obese and lean rats 30 min after intraperitoneal injection of rabbit serum with CCK-AB were greater than those after intraperitoneal injection of rabbit serum without CCK-AB (1.92 vs. 1.41, g, p less than 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

The neurophysiological regulation of growth hormone secretion.

With the advent of genetic engineering, the importance of GH in the regulation of growth and metabolism in domestic species has been clearly demonstrated. Ample evidence of an integral role for GH in the processes of growth and lactation exists in dairy cattle (1,2), sheep (3), beef cattle (4) and swine (5). For example, circulating GH levels are high during the period of rapid growth in several species including cattle (6), swine (7) and poultry (8). Endogenous GH secretion is primarily controlled by the central nervous system (CNS) via two specific hypothalamic neurohormones, growth hormone-releasing factor (GRF) and somatostatin (SRIF), an inhibitor of GH release. The secretion of GRF and SRIF is governed by a host of neuropeptides and neurotransmitters which provide a functional link between higher CNS centers and hypophysiotropic neurons. This review will focus on the CNS regulation of GH secretion and circulating factors which feedback to either stimulate or inhibit its release.

Recombinant bovine somatotropin stimulates short term increases in growth rate and insulin-like growth factor I (IGF-I) in chickens.

Recombinant bovine somatotropin (rbGH) was administered by subcutaneous injection at daily doses of 0.5 or 2.5 mg/kg for a two week period in female broiler chicks between 4 and 6 weeks of age. Half of the chicks received dietary corticosterone at a 1 ppm level. Growth rate was significantly increased 6.1% and 6.9% following one week of treatment with 0.5 or 2.5 mg/kg rbGH respectively. Treatment with the same respective doses of rbGH in the presence of 1 ppm corticosterone, supplied to suppress any possible immune response elicited by the heterologous somatotropin, resulted in an 8.0% and 7.8% increase (P less than .05) in growth rate during the first week of treatment. The rbGH-associated increase in growth rate was accompanied by a significant increase in food intake, higher circulating levels of IGF-I, and lower plasma T4 concentrations, while plasma T3 levels were unchanged. All effects were attenuated during the second week of treatment, concomitant with the development of high antibody titer against rbGH regardless of dietary corticosterone administration. Carcass parameters relating to bone, muscle and fat were not different between rbGH-treated and control chickens at the end of the two week treatment period. Thus rbGH is capable of stimulating a short-term improvement in growth rate, which is related to increased feed consumption and is of limited duration.

Ontogeny of growth hormone (GH), insulin-like growth factors (IGF-I and IGF-II) and IGF binding protein-2 (IGFBP-2) in genetically lean and obese swine.

Serum GH, IGF-I, IGF-II and IGFBP-2 concentrations were determined by radioimmunoassay in swine of genetic lines which were selected for high (obese) and low (lean) backfat. Blood samples were collected at birth, before and after nursing, at 1 and 3 days of age and at weekly or fortnightly intervals until 30 weeks of age. Overall, GH, IGF-I, IGF-II and IGFBP-2 were highest at birth and declined during the first week of postnatal life. An age-by-line interaction was apparent for GH and IGF-I during the early neonatal period with levels being higher in the lean line than the obese line at 1 day of age and similar at 1 week of age. At 3 to 5 weeks of age there was an elevation in GH which was greater in lean than obese pigs. IGFBP-2 concentration patterns were characterized by a nadir at 5 to 7 weeks of age and a decline from an apex at 8 weeks of age in both lines. IGF-II declined steadily from birth until about 10 weeks of age. A subsequent increase in IGF-II was then observed between 12 and 22 weeks, which was greater in the obese line and in male pigs but not apparent in lean females. At birth, pigs which had not nursed had higher GH and IGFBP-2 and lower IGF-I and IGF-II concentrations. The effect of nursing on IGF-I was significantly influenced by line.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of insulin-like growth factor 1 (IGF1) and IGF binding protein levels in swine.

A heterologous radioimmunoassay system was validated for the determination of IGF1 concentrations in swine sera. Parallelism, accuracy and response to physiological stimuli were obtained following the incubation of serum samples with 1M glycine-glycine HC1 buffer at a pH of 3.5 +/- 0.2 for 24 hours at 37C. Following acidification and neutralization, circulating IGF1 concentrations were significantly (P less than .05) reduced in hypophysectomized swine and elevated in swine injected with porcine growth hormone (pGH) when compared to IGF1 levels in control hogs. IGF binding protein levels were also increased following GH administration and reduced by hypophysectomy. In addition, circulating IGF1 concentrations were significantly (P less than .05) correlated with body size in three types of swine which differ in growth rate and mature body weight. These data suggest that IGF1 is involved in the regulation of swine growth in vivo and that its physiologic regulation is similar to that in humans.

Interactions between environmental temperature and porcine growth hormone (pGH) treatment in neonatal pigs.

Age-dependent interactions between environmental temperature and porcine growth hormone (pGH) treatment on the function of the somatotrophic axis were evaluated in the neonatal pig. At 3 d of age, 40 Landrace x Yorkshire x Duroc piglets received intraperitoneal implants containing either recombinant pGH (0.5 mg/d; n = 20) or vehicle (control; n = 20). Piglets were maintained at either a low (21 degrees C, 50% relative humidity; n = 20) or high (32 degrees C, 50% relative humidity; n = 20) temperature. At 4 and 6 wk of age, 5 pGH-treated and 5 control piglets from each thermal group were sacrificed for tissue collection. Blood samples were collected at the time of sacrifice and analyzed for serum concentrations of GH, insulin-like growth factor 1 (IGF-1), and IGF-2. Liver RNA was analyzed for mRNAs specific for the GH receptor, IGF-1, IGF-2, and IGF binding protein 3. There was no effect of pGH treatment (P = 0.4) on average daily gain; however, both age (P = 0.002) and temperature (P = 0.001) had an effect on average daily gain such that those animals maintained at a low temperature and those sacrificed at 6 wk had greater average daily gains. Serum concentration of GH was elevated (P = 0.003) by pGH treatment and was lowest in the 6-wk-old group (P = 0.008). Serum concentration of IGF-1 was elevated (P = 0.007) by pGH treatment and increased with age (P = 0.01). Liver GH receptor mRNA was unaffected (P > 0.5) by pGH treatment, but was greater in the 6-wk-old group (P < 0.0001) and in piglets maintained at the high temperature (P = 0.04). IGF-1 mRNA was enhanced by pGH treatment (P = 0.0003) and by exposure to the high temperature (P = 0.04), but did not differ (P > 0.5) between age groups. IGF-2 mRNA was greater (P = 0.0009) in the 4-wk-old group and in piglets maintained at the high temperature (P = 0.007), but was unaffected (P = 0.5) by pGH treatment. IGF binding protein 3 mRNA increased with age (P = 0.0004) and was stimulated by pGH treatment in the 6-wk-old group (P = 0.034). The relatively lower level of GH receptor and IGF mRNAs in conjunction with greater growth in the cold environment suggests that somatotrophic gene expression in the liver is not rate limiting for growth in the neonatal pig.

Suppression of somatotroph function induced by growth hormone treatment in neonatal pigs.

The effect of recombinant porcine growth hormone (pGH) treatment on pituitary function was evaluated in young pigs. Piglets received intraperitoneal recombinant pGH implants (0.5 mg/d sustained release) or vehicle implants beginning at 3 d of age. Ten piglets were sacrificed at 4 and 6 wk of age (five piglets/treatment group) for the collection of pituitary glands, blood, and liver tissue. Blood samples also were drawn at 3 and 12 d of age. Serum concentrations of GH, prolactin (PRL), thyroid-stimulating hormone (TSH), insulin-like growth factor-1 (IGF-1) and IGF-2 were evaluated. Levels of IGF-1 and IGF-2 mRNA were determined in liver samples. Treatment with GH increased circulating levels of GH and IGF-1 (P < 0.01), but not PRL, TSH, or IGF-2. Hepatic IGF-1, but not IGF-2, mRNA levels were increased by pGH (P < 0.001). Cultured pituitary cells from each animal were challenged with 0.1, 1, and 10 nM GH-releasing hormone (GHRH); 2 nM 8-Br-cAMP; or 100 nM phorbol myristate acetate. The release of GH from cultured pituitary cells was stimulated by all secretagogues (P < 0.001). The secretion of GH, but not PRL or TSH, in culture was inhibited by previous in vivo GH treatment (P < 0.001). Similarly, cellular GH, but not PRL or TSH, content was lower in the GH-implant group (P = 0.005). Cell cultures from 6-wk-old piglets secreted more GH, but not PRL or TSH, than cultures from 4-wk-old piglets (P < 0.05). Likewise, cellular GH, but not PRL or TSH, content was greatest in cultures from 6-wk-old animals (P = 0.002). Piglet growth was not affected by exogenous GH treatment (P = 0.67). These results demonstrate that exogenous pGH treatment selectively down-regulates somatotroph function in young pigs.

Effects of somatostatin immunoneutralization on growth and endocrine parameters in chickens.

The effects of somatostatin immunoneutralization on growth rate, growth hormone (GH) secretion and circulating insulin-like growth factor I (IGF-I) concentrations were investigated in chickens through the use of passive and active immunization techniques. Intravenous bolus injection of goat-antisomatostatin stimulated a significant (P less than .05) increase in plasma GH levels for one hour post-injection in four and six week old male broiler chickens. The GH response to an intravenous bolus injection of hGRF44NH2 was similar in the antisomatostatin treated chicks and normal goat serum treated controls. Despite the presence of circulating somatostatin antisera after 28 hours, plasma GH levels were not different between control and antisomatostatin-treated chicks at that time. Continuous administration of somatostatin antisera by Alzet pump over a two-week period resulted in significant (P less than .05) elevations in plasma GH levels at one week post-implantation and in circulating IGF-I concentrations after two weeks of administration. Chicks which developed antibodies against somatostatin following active immunization exhibited a 7.1% increase in growth rate which was associated with a significant decrease in abdominal fat. However, neither GH nor IGF-I concentrations were elevated in the chicks which developed somatostatin antibodies. Thus, the benefits gained from somatostatin immunoneutralization may be exerted through mechanisms other than GH.