Administration Of pGH Research Articles

Porcine skin gelatin hydrolysate as a dipeptidyl peptidase IV inhibitor improves glycemic control in streptozotocin-induced diabetic rats

The peptides (PGH) in the < 1 kDa ultrafiltration (UF) fraction of the porcine skin gelatin hydrolysates obtained by Flavourzyme® (FLA) hydrolysis showed the greatest in vitro dipeptidyl peptidase IV (DPP-IV) inhibitory activity and were used for an in vivo animal experiment. PGH comprises three peptides with a molecular mass between 742.327 and 780.276, and one of the peptides had Pro as the penultimate N-terminal residue and showed DPP-IV inhibitory activity. The daily administration of PGH (300 mg/day for 42 days) was able to improve the glucose tolerance in streptozotocin-induced diabetic rats at days 21 and 42. After 42 days of treatment, the plasma DPP-IV activity was inhibited, and the glucagon-like peptide-1 (GLP-1) and insulin levels increased, accompanied by an insignificant reduction in the glucagon content. Therefore, porcine skin gelatin has potential as a functional food for the management of type 2 diabetes mellitus.

Effect of Exogenous Porcine GH Administration on GH Responses to GH-releasing Peptide-2 and GH-releasing Hormone in Swine

Negative feedback on GH responses to GH-releasing hormone (GHRH) and GH-releasing peptides (GHRPs) has been reported and this action has been suggested to act through an increase in somatostatin. To determine whether the acute administration of porcine GH (pGH) inhibits GH responsiveness to GHRP-2 and GHRH in swine, swine were intravenously administered with pGH (5 µg/kg BW) or placebo followed 180 min later by a second intravenous administration of saline, GHRP-2 (30 µg/kg BW), GHRH (1 µg/kg BW) and a combination of GHRP-2 and GHRH. Plasma GH concentration was measured by radioimmunoassay. Administration of pGH caused a significant increase in GH area under curve and GH peak concentrations (p<0.001) over placebo-treated group. Plasma GH concentrations peaked at 15 min and returned to baseline level within 90 min. Pretreatment of pGH abolished (p<0.01) GH response to GHRH and attenuated (p<0.05) GH response to GHRP-2 and GHRH combined, without affecting GH response to GHRP-2. These results demonstrate that negative feedback action on GH releasing effect of GHRH occurs in swine, and that GHRP-2 has ability to interact in this action. (Asian-Aust. J. Anim. Sci. 2003. Vol 16, No. 8 : 1188-1192)

Growth, body composition, and endocrine responses to chronic administration of insulin-like growth factor I and(or) porcine growth hormone in pigs.

The actions of IGF-I, alone and in combination with porcine growth hormone (pGH), on growth and circulating endocrines and metabolites important in growth were investigated in peripubertal-age Meishan barrows. Pigs were assigned to four treatments: control, buffer; IGF-I, 33 microg rhIGF-I/kg BW injected twice daily; pGH, 33 microg rpGH/kg BW injected once daily; and IGF-I+pGH, 33 microg rhIGF-I/kg BW injected twice daily plus 33 microg rpGH/kg BW injected once daily. Treatments were administered for 28 d. Feed intake, BW, and backfat were recorded and blood samples were collected weekly. At slaughter, organ and primal cut weights were recorded. Offal and half the carcass were ground for chemical analysis. Serum concentrations of IGF-I on d 7, 14, 21, and 28 in the IGF-I, pGH, and IGF-I+pGH groups were increased 60, 107, and 131%, respectively, compared with those of the control group. Administration of pGH increased gain 43%, feed efficiency 60%, carcass protein accretion 88%, and trimmed lean cuts 16%, whereas IGF-I administration increased gain 22%, carcass protein accretion 33%, and trimmed lean cuts 5%. There was little difference in responses to administration of IGF-I+pGH and pGH alone except that coadministration of IGF-I with pGH reduced the ability of pGH to suppress backfat gain (P < .02). Even though administration of IGF-I resulted in a 60% increase in chronic nadir serum concentrations of IGF-I, only a few growth and carcass measures were changed when compared with control pigs. These included increased (P < .05) weight of body, leaf fat, kidneys, and belly. The actions of pGH on growth of pigs were not mimicked, and some were countermanded by administration of IGF-I at a dose that produces significantly increased serum concentrations of IGF-I.

Regulation of insulin-like growth factor-binding proteins in rats with insulin-dependent diabetes mellitus.

As previously reported, activation of the adrenocorticotropic hormone (ACTH)-adrenal cortical axis in rats with insulin-dependent diabetes mellitus (IDDM) reduces their growth and circulating insulin-like growth factor-I (IGF-I) levels and induces a resistance to growth hormone (GH) and IGF-I. The studies reported herein were conducted to determine whether the pituitary and/or adrenal gland influence the changes in basal and GH-stimulated serum concentrations of IGF-binding proteins (IGFBPs) in rats with IDDM. Male rats were made diabetic by injections of streptozotocin. Intact nondiabetic (NonDb), diabetic (Db), hypophysectomized diabetic (HxDb), and adrenalectomized diabetic (AxDb) rats were injected twice daily with 50 micrograms porcine (p) GH or with 0.9% saline for 2 weeks following the surgeries. Changes in serum IGFBP concentrations were determined by Western ligand- or immuno-blot analysis. Neither IGFBP-5 nor -6 was detected in any of the treatment groups. Induction of IDDM increased serum concentrations of IGFBP-1 and -2 and reduced those of IGFBP-3 and -4. Although serum IGFBP-1 and -2 concentrations remained elevated in the HxDb rats compared with the NonDb controls, IGFBP-1 levels were reduced compared with those in the Db controls. Serum IGFBP-3 and -4 were reduced to levels below those in Db controls. Although IGFBP-3 and -4 concentrations were elevated to normal in AxDb rats, the IGFBP-2 concentration was increased above those in both NonDb and Db rats and the IGFBP-1 concentration was reduced. Administration of pGH increased serum IGFBP-4 concentrations in all groups and IGFBP-3 concentrations in all groups except the Db. In addition, pGH reduced the concentration of IGFBP-1 in HxDb rats and nearly abolished it in AxDb rats, but had no effect on IGFBP-1 concentration in NonDb or Db rats. Administration of corticosterone (B; 25 micrograms/ml of 0.9% saline drinking water) to AxDb rats restored Db-like profiles of all IGFBPs. The refractoriness of Db rats to pGH is associated with a failure of the hormone to elevate IGFBP-2 and -3 titers and to reduce those of IGFBP-1. Adrenal B production appears to be responsible for this resistance to GH. However, the elevated IGFBP-2 concentration in Db rats does not appear to be due to B or any other pituitary-controlled or -derived factors. Impaired growth was associated with substantially reduced IGFBP-3 concentrations and elevated IGFBP-1, whereas growth restoration was associated with the opposite changes.

Hypophysectomy or Adrenalectomy of Rats with Insulin-Dependent Diabetes Mellitus Partially Restores Their Responsiveness to Growth Hormone

The studies reported herein were conducted to confirm that the pituitary gland is involved in maintaining growth hormone (GH) resistance in rats with insulin-dependent diabetes mellitus (IDDM) and to determine whether the adrenocorticotropic hormone (ACTH)-adrenal cortical axis is responsible. The rats were made diabetic by injecting streptozotocin (85 mg/kg body wt) IP once daily on two consecutive days. They were then injected with 15 IU insulin SC twice daily on two consecutive days to enable them to survive hypophysectomy or adrenalectomy. Intact nondiabetic (NonDb), diabetic (Db), hypophysectomized diabetic (HxDb), and adrenalectomized diabetic (AxDb) rats were injected twice daily with 50 micrograms porcine (p) GH or with 0.9% saline for 2 weeks following the surgeries. Serum glucose levels of the saline-injected Db, HxDb, and AxDb rats were significantly greater than those of the NonDb rats by 106%, 65% and 49%, respectively. However, the levels in the HxDb and AxDb animals were significantly lower than those of the Db group by 20% and 28%, respectively. Injections of pGH into NonDb rats increased serum glucose concentrations by 38%, over their saline-treated controls, and by 29% in AxDb rats. This diabetogenic effect of GH was not seen in any other group. Administration of pGH to Db rats failed to increase body weight gain, tall growth, tibial epiphysial plate width, or serum IGF-I concentration over saline-injected controls. By contrast, HxDb and AxDb rats injected with pGH showed significant increases in all four growth parameters. Total serum IGF-I concentrations in AxDb rats injected with pGH equaled those in NonDb controls. To determine whether the lack of corticosterone (B) in the AxDb rats was responsible for the reduced hyperglycemia and restored responsiveness to pGH, AxDb rats were given B in their drinking water at 5 or 25 micrograms/ml. Administration of B reduced the beneficial effects of adrenalectomy by restoring hyperglycemia and growth impairment, and partially restored resistance to the pGH injections. These studies confirm that the pituitary contributes to diabetic growth impairment and show that the ACTH-adrenal cortical axis is primarily responsible for the GH-resistant state that develops in rats with IDDM.

Effect of frequency of administration of exogenous porcine growth hormone on growth and carcass traits and ovarian function of prepubertal gilts.

Three experiments were conducted to examine relationships among dose and frequency of administration of exogenous porcine growth hormone (pGH) on growth traits and ovarian function of prepubertal gilts. In Exp. 1, gilts were treated with 0 or 5 mg of pGH daily for 42 d or 5 mg of pGH daily on alternate weeks over a 42-d period. In Exp. 2, gilts were treated with 0, 2.5, or 5 mg of pGH daily for 31 d or daily on alternate weeks for 31 d. In Exp. 3, gilts received 5 mg of pGH daily on either wk 1, 3, and 5 or wk 2, 4, and 6 during a 42-d period. In all experiments, ADG increased dramatically and feed efficiency improved markedly during treatment with pGH, and both traits declined rapidly during periods when treatment was withdrawn. Gilts treated with pGH daily on alternate weeks tended to be more similar (P greater than .05) to control gilts for growth rate, feed efficiency, and carcass measurements than to gilts that received continuous daily administration of pGH during the entire duration of the experiments. Increased concentrations of estradiol and insulin-like growth factor (IGF)-I in follicular fluid and serum, decreased concentrations of IGF-II in follicular fluid, and increased weights of ovaries were evident as both dose and frequency of exogenous pGH administration increased. Therefore, gilts are extremely sensitive to administration and withdrawal of exogenous pGH during the finishing phase of the production cycle and can respond within 7 d to changes in exogenous pGH treatment regimens. Alternate weekly administration of exogenous pGH in vivo may improve follicular function, as indicated by relationships among IGF-I and IGF-II, estradiol, and progesterone, but fails to improve overall growth and carcass traits compared with controls.

Growth hormone binding proteins in pig adipose tissue: Number, size and effects of pGH treatment on pGH and bGH binding

The present study was undertaken to determine the number and size of growth hormone binding proteins present in pig adipose tissue, determine if there were differences in binding of pGH and bGH to adipose tissue membranes and establish the effects of pGH treatment on GH binding. Administration of pGH (0, 25, 50 or 100 μg pGH/kg BW/d) for 7 d did not affect binding of [ 125I]bGH to adipose tissue microsomes. Maximum binding of bGH was approximately 8-fold higher than that observed for pGH. Half-maximal inhibition of [ 125I]bGH binding was observed at 11 ng/ml of bGH. In contrast, a more than 10-fold greater concentration of pGH was required to half-maximally inhibit [ 125I]pGH binding. bGH and pGH both bound to the same GH binding proteins (Mr of 92,000, 73,000 and 53,000). The GH binding proteins appear to be produced by post-translational modification of a single GH receptor transcript rather than alternative splicing of a primary transcript since only one GH receptor mRNA transcript (4.2 kb) was detected on Northern analysis. Our findings indicate that: 1) bGH is the preferred ligand to use to study GH binding in pig adipose tissue membranes (or adipocytes); 2) exogenous pGH does not alter GH binding; and 3) only one GH receptor mRNA transcript is present in pig adipose tissue.

Effects of exogenous porcine growth hormone on serum insulin-like growth factor-binding proteins in growing pigs

The insulin-like growth factor-binding proteins (IGFBPs) in sera of growing pigs were partially characterized with respect to their size, immunological relationships to other known IGFBPs and their regulation by porcine (p) GH. Castrated male pigs (14-16 weeks of age) were treated with either vehicle or pGH (up to 100 micrograms/kg body weight per day) by daily i.m. injection for 7 days. Blood samples were collected by jugular venepuncture at the time of injection. Five IGFBPs of 43, 40, 34, 30 and 26 kDa were identified on ligand blots of porcine sera. A 30 kDa IGFBP, in addition to the 43 and 40 kDa IGFBPs, was immunoprecipitated by antiserum to pIGFBP-3 and found to contain N-linked carbohydrate suggesting that it is a fragment of pIGFBP-3 as has been noted for a 29 kDa N-glycosylated IGFBP in rat sera. The 34 kDa IGFBP in pig sera was precipitated by antisera to rat IGFBP-2 and contained no N-linked carbohydrate. Administration of pGH to normal growing pigs not only increased pIGFBP-3 levels but elicited a dose-dependent suppression of levels of the 34 kDa IGFBP as well. In summary, the Mr pattern of IGFBPs in the sera of growing pigs is similar to that observed in fetal and maternal pig sera and in other species. Furthermore, we report that administration of pGH to normal pigs suppresses the expression of an IGFBP-2-like IGFBP in pig sera while increasing expression of pIGFBP-3.

Growth hormone increases insulin-like growth factor-I (IGF-I) and decreases IGF-II in plasma of growing pigs

Insulin-like growth factor-I (IGF-I) and IGF-II have been measured in plasma obtained from male and female pigs of two strains during daily administration of pituitary-derived porcine GH (pGH; 100 micrograms/kg) from 60 to 90 kg body weight. Each plasma sample was first chromatographed to separate the IGF from binding proteins in order to obtain reliable measurements. IGF-I concentrations showed no differences between strains, but were higher in untreated males (497 +/- 43 (S.E.M.) micrograms/l) than females (299 +/- 15 micrograms/l). GH-treated animals had two-fold higher concentrations of IGF-I. IGF-II concentrations were not significantly different between sexes or strains, but were decreased in pigs treated with pGH (299 +/- 28 micrograms/1) compared with controls (431 +/- 32 micrograms/l). Binding protein concentrations, measured as interference in the IGF-I and IGF-II assays, were not different between sexes or strains, but were increased in pGH-treated animals. Taken together, these results indicate that in addition to the expected increase in IGF-I concentrations, exogenous administration of pGH to pigs leads to an increase in IGF-binding protein and a depression in IGF-II concentrations.

Interaction of dietary protein content and exogenous porcine growth hormone administration on protein and lipid accretion rates in growing pigs.

Sixty-six intact male pigs were used to investigate the relationships between exogenous porcine growth (pGH) administration (0, excipient-treated, and .09 mg recombinant pGH.kg-1.d-1) and dietary protein content (8.3, 11.4, 14.5, 17.6, 20.7 and 23.8%) on protein and lipid accretion rates over the live weight range of 30 to 60 kg. Feed intakes were restricted (1.84 kg.pig-1.d-1) and pGH was administered daily by i.m. injection. Rate of protein deposition increased with increasing dietary protein up to 17.6 and 20.7%, respectively, for control and pGH-treated pigs; both growth and protein deposition were enhanced by pGH on the four higher protein diets but remained unaffected by pGH administration to pigs given the two lowest protein diets. Plasma IGF-I concentration was elevated by pGH administration in pigs given the four higher protein diets but unaffected by pGH with the two lowest protein diets. Rate of fat deposition was depressed on all dietary protein treatments by pGH administration; carcass fat content of control and pGH-treated pigs declined with each increase in dietary protein up to 17.6 and 23.8%, respectively. The results demonstrate that pGH acts independently on protein and lipid metabolism.

Effect of GH status on IGF-I and IGF-II concentrations and serum IGF binding profiles in pigs.

The present study was conducted to determine 1) whether porcine growth hormone (pGH) affected insulin-like growth factor (IGF)-II concentrations in growing pigs and 2) the distribution of [125I]IGF-I and [125I]IGF-II binding activity and immunoreactive IGF-I and IGF-II in serum from control, pGH-treated and hypophysectomized (hypox) pigs. Seven weeks of pGH treatment had no effect on serum IGF-II concentrations, but after 11 wk serum IGF-II had increased by up to 50%. In normal pig serum, [125I]IGF-I bound to specific insulin-like growth factor binding proteins (IGF-BP) of 40 kDa (87.5%) and 150 kDa (12.5%). Treatment with pGH increased the proportion of IGF-I bound to the large IGF-BP (approximately 48%). In contrast, [125I]IGF-II partitioned to specific IGF-BP of 450 kDa (30%), 150 kDa (46%) and 40 kDa (23%). After treatment with pGH, binding of IGF-II to the 150-kDa IGF-BP increased to 57% of total specific binding. Binding of IGF-I and IGF-II to the 150-kDa IGF-BP was virtually abolished in hypox pig serum. IGF-I immunoreactivity was predominantly associated with the 150-kDa IGF-BP (67 to 83%), with the remainder bound to the small IGF-BP. There was no detectable free IGF-I in pig serum. Treatment with pGH did not affect the distribution of immunoreactive IGF-I between the two IGF-BP complexes, although there was a marked elevation in total serum IGF-I concentration. Immunoreactive IGF-II was detected in all three IGF-BP complexes. In control serum, the largest quantity (46%) of immunoreactive IGF-II was associated with the 40-kDa IGF-BP. Thirty-four percent was bound to the 150-kDa IGF-BP complex. Administration of pGH led to an increased association with the 150-kDa complex (50%) and a concomitant decrease in IGF-II associated with the 40-kDa species (35%). In summary, IGF-II concentrations in the pig are elevated by prolonged pGH treatment. Furthermore, there is a unique large IGF-BP in postnatal pig serum that specifically binds IGF-II but not IGF-I.

Effects of gender and genotype on the response of growing pigs to exogenous administration of porcine growth hormone.

Sixty crossbred pigs (Large White x Landrace) were used in a 2 x 2 x 2 factorial experiment to investigate the effects of gender (intact males vs females) and strain (A vs B) on the response to exogenous porcine growth hormone (pGH) administration (0 [excipient-treated] vs .1 mg pGH.kg live weight-1.d-1). All pigs had ad libitum access to their diet; pGH was administered daily from 60 to 90 kg live weight. All aspects of growth performance and body composition were affected to different degrees by gender and pGH. Strain A pigs had a higher capacity for protein accretion, superior growth performance and contained less fat in the eviscerated carcass and empty body compared with Strain B pigs. Within each strain, intact males ate more feed, had a higher rate of protein deposition and exhibited faster and leaner growth than females. Exogenous pGH administration increased average protein deposition and growth rate by 84 and 34%, respectively, and reduced average feed intake, fat deposition rate, feed:gain and carcass fat content by 14, 59, 37 and 33%, respectively. The magnitude of the changes in growth performance, tissue accretion rates and body composition elicited by pGH were independent of strain. However, within each strain the improvement in feed:gain and reduction in carcass fat measurements elicited by pGH were proportionately larger for females than for intact males.

Effects of exogenous porcine growth hormone administration between 30 and 60 kilograms on the subsequent and overall performance of pigs grown to 90 kilograms.

Twenty-eight barrows were used to investigate the effects of exogenous porcine growth hormone (pGH) administration (0 and 100 micrograms.kg-1.d-1) between 30 and 60 kg on the subsequent and overall performance and carcass composition of pigs grown to 90 kg. The pGH was administered by daily i.m. injection and all pigs were fed one diet. Control animals were pair-fed to the intake noted for pGH-treated pigs between 30 and 60 kg and all pigs were fed ad libitum from 60 to 90 kg. Pigs administered pGH had an improved rate (36%) and efficiency (28%) of gain and an improved protein accretion rate (46%) compared to excipient-treated pigs. Pigs previously treated with pGH continued to exhibit superior (P less than .01) rate and efficiency of gain, and the gain was associated with enhanced protein accretion during the quiescent (postinjection) period compared with excipient counterparts. Administration of pGH between 30 and 60 kg reduced carcass fat and increased carcass protein and water at 90 kg, although fat accretion rate was comparable to that of control pigs. Results indicate that, to varying degrees, the stimulatory effects of pGH on growth performance are sustained following cessation of hormone treatment.

Interrelationships between sex and exogenous growth hormone administration on performance, body composition and protein and fat accretion of growing pigs.

Forty-five pigs with an average initial live weight of 60 kg were used to investigate the effects of daily exogenous porcine pituitary growth hormone administration at two dose levels (pGH; 0, excipient buffer injected, and 100 micrograms.kg-1.d-1) for a 31-d period on the performance and body composition of boars, gilts and barrows allowed to consume feed ad libitum. Excipient boars consumed less feed, exhibited faster and more efficient growth (P less than .01) and produced less fat and more protein and water (P less than .01) in the empty body compared with excipient barrows, which in turn contained more fat and less water (P less than .05) in the empty body than did excipient gilts. These differences were largely eliminated by pGH administration, which induced differential effects in growth performance and body composition in boars, gilts and barrows. Growth hormone administration improved growth rate by 13, 22 and 16% and feed conversion efficiency by 19, 34 and 32% in boars, gilts and barrows, respectively. The reduction of body fat content (g/kg) elicited by pGH was 22, 36 and 33% for boars, gilts and barrows, respectively, with a corresponding increase (P less than .01) of body protein and water content. The magnitude of the pGH responses was greatest for gilts and barrows compared with boars, negating intrinsic sex-effect differences in growth performance and body composition of pigs. Pigs used in this study and treated with pGH exhibited a rate of protein deposition (approximately 225 g/d) far greater than previously reported, and as such redefine the genetic capacity for lean tissue growth by the pig.

Effects of porcine growth hormone on glucose metabolism of pigs: I. Acute and chronic effects on plasma glucose and insulin status.

The acute and chronic effects of porcine growth hormone (pGH) administration on glucose homeostasis of pigs were investigated in the present study. Twelve Yorkshire barrows (average BW = 65 kg) fitted with femoral artery catheters were allotted to three groups. Pigs received acute, intra-arterial injections of either pituitary pGH, a recombinantly derived pGH analog (ppGH or rpGH, 100 micrograms/kg BW) or saline. Acute injection of pGH did not affect fasting plasma glucose or insulin status. Pigs then were treated daily by i.m. injection for 24 d with 70 micrograms ppGH/kg BW. Serum glucose and insulin concentrations during the fed and fasted states were higher in pGH-treated than in control pigs. On d 25, an acute intra-arterial injection of ppGH (100 micrograms/kg BW) elicited increases in plasma glucose and insulin in pigs chronically treated with pGH. The area circumscribed by the glucose and insulin response curves 5 min to 7 h postinjection was 40% (P less than .005) and 177% (P less than .001), respectively, higher in ppGH-treated than in control pigs. These data indicate that pGH does increase plasma glucose and insulin in the fed and fasted states; however, this response is only observed after chronic pGH administration. In addition, pGH is capable of increasing plasma glucose and insulin acutely in the pig. This effect, however, only is observed in pigs treated chronically with pGH. The mechanisms by which pGH elicit these effects on glucose homeostasis are not known.

Stimulation of in vitro muscle cell proliferation by sera from swine injected with porcine growth hormone.

The proliferation-promoting activity of sera obtained from pigs before and after porcine growth hormone injections was tested in a muscle cell culture bioassay. For 3 d, purified porcine growth hormone (pGH) was administered by intramuscular injection to crossbred barrows. Two levels of pGH were administered: 18 micrograms pGH X kg-1 body weight X d-1 (low dose) or 143 micrograms pGH X kg-1 body weight X d-1 (high dose). Multiple blood samples were withdrawn from jugular catheters for 3 d prior to the injection, during the injection period and for 6 d after the last injection. Although serum pGH levels in low-dose pigs were raised from two to three times pre-injection levels, there was no significant change in serum proliferation-promoting activity or somatomedin-C (SmC), insulin or cortisol levels during or after administration of pGH. In contrast, the proliferation-promoting activity of sera obtained during and after the high-dose pGH injections was higher (P less than .005) than the pre-injection levels. Serum pGH levels were increased approximately 30-fold by 4 h after each injection, and increases in SmC levels were observed 10 to 16 h after the pGH injection. During the injection period SmC levels increased from 1.7 to 4 times pre-injection levels. Insulin and cortisol levels did not change significantly during the 3-d treatment period. We believe that this muscle cell culture bioassay system will be a useful addition to traditional radioimmunoassays and whole animal studies in elucidating the mode of action of pGH in pituitary-intact swine.

Characterization of porcine growth hormone (pGH) binding to porcine liver microsomes: chronic administration of pGH induces pGH binding.

The effect that GH has on regulating GH binding to its receptors has not been resolved. This report describes the characterization of porcine (p) GH binding to pig liver membranes and clarifies the issue of regulation of GH binding by measuring pGH binding to liver membranes prepared from pigs treated daily for 35 days with different doses of pGH (0, 10, 30, or 70 micrograms/kg BW). Specific binding of [125I]pGH was dependent on time, pH, and membrane protein concentration. At 23 C, pGH binding reached a steady state after 24 h. Maximal pGH binding was observed at pH 7. Binding increased linearly as membrane protein concentration was increased from 150 to 450 micrograms/tube. Specificity studies indicated that the hepatic GH receptor was somatogenic, since porcine PRL poorly inhibited [125I] pGH binding (cross-reactivity, 0.1%). Treatment of microsomes from control pigs with 4 m MgCl2 to remove endogenously bound pGH did not affect pGH binding, whereas binding was significantly increased to microsomes from pGH-treated pigs. Binding of pGH increased in a linear manner with the dose of pGH given for 35 days (r = 0.79), thus establishing the inductive effect of chronic pGH administration on pGH binding in pig liver. GH binding was highly correlated with weight gain in pigs treated with pGH (r = 0.76). In addition, the serum insulin-like growth factor I (IGF-I) concentration was increased linearly (r = 0.87) by pGH. This increase in serum IGF-I was also highly correlated with the increase in pGH binding (r = 0.71). These results suggest that hepatic GH binding plays an important role in regulating pig growth, which may be mediated, in part, by an increase in hepatic IGF-I synthesis and secretion. The present report is also the first to establish that exogenous pGH induces pGH binding to pig hepatic GH receptors and to relate this increase in binding to an enhancement in pig growth.

Stimulation of swine growth by porcine growth hormone.

Highly purified porcine growth hormone (pGH; USDA-B1) was administered by im injection (22 micrograms X kg body weight-1 X d-1) to rapidly growing Yorkshire barrows for 30 d. Growth hormone significantly increased growth rate (10%), feed efficiency (4%), cartilage growth and muscle mass. However, pGH did not affect carcass adipose tissue mass. Intramuscular lipid content of the longissimus was increased 50% by pGH administration. Plasma pGH concentration was elevated (7- to 11-fold) for 3 to 5 h post-injection. Chronic administration of pGH depressed pituitary GH content and concentration approximately 45%. No GH antibodies were detected in the plasma of GH-treated swine. Plasma somatomedin-C concentration was increased 55% by GH treatment 3 h post-injection. Plasma glucose and insulin concentrations were both significantly increased in GH-treated swine, suggesting that the animals had developed a state of insulin resistance. Plasma-free fatty acid concentration tended to be higher in GH-treated animals. Treatment of swine with pGH significantly decreased plasma blood urea nitrogen. Assessment of animal health during the trial and postmortem indicated that pGH administration did not have any adverse effects. In summary, treatment of young, rapidly growing swine with pGH stimulated growth performance without affecting animal health or inducing the production of GH antibodies.