Ontogeny of IGF-I responsiveness to bGH in young lambs

The ontogeny of hepatic growth hormone (GH) receptors (GHR), as measured by responses of both plasma insulin-like growth factor-I (IGF-I) and hepatic GHR to an exogenous bGH stimulus, was examined using sheep of different ages (Days 1-7, 14-21, 28-35, and 56-63 of life, and yearlings). The IGF-I response to bGH was first examined in yearling sheep using two doses of bGH (0.1 and 0.2 mg/kg LW/d). Based on these results, lambs in four groups up to Day 63 of life were treated for 5 d with bGH (n = 10) at a dose of 0.15 mg/kg LW/d or with saline (n = 10). Jugular blood samples were taken once daily on Days - 1, 4, and 5 of treatment. bGH treatment in lambs up to Day 63 of life had little effect on plasma concentrations of GH, insulin, glucose or urea, but significantly (P < 0.05) increased circulating concentrations of IGF-I at all ages and of NEFA at Day 62/63 of life. In contrast, bGH treatment at either dose in yearlings significantly increased these parameters, except for plasma urea concentrations which were decreased in bGH-treated yearlings. However, the responses of plasma IGF-I concentration to bGH stimulus in lambs up to Day 63 of life were small compared to those in yearling sheep. Consistent with this, bGH treatment failed to affect hepatic GH binding in young lambs, but up-regulated it in yearling sheep. Furthermore, basal (unstimulated) GH binding did not differ between sheep of 7 vs. 63 vs. 365 d of age, despite the greater IGF-I responses to bGH in the latter group. It is suggested that hepatic GHR in lambs up to Day 63 of life are not fully functional compared to the situation in yearlings.     

Ontogeny of IGF-I responsiveness to bGH in young lambs

The ontogeny of hepatic growth hormone (GH) receptors (GHR), as measured by responses of both plasma insulin-like growth factor-I (IGF-I) and hepatic GHR to an exogenous bGH stimulus, was examined using sheep of different ages (Days 1-7, 14-21, 28-35, and 56-63 of life, and yearlings). The IGF-I response to bGH was first examined in yearling sheep using two doses of bGH (0.1 and 0.2 mg/kg LW/d). Based on these results, lambs in four groups up to Day 63 of life were treated for 5 d with bGH (n = 10) at a dose of 0.15 mg/kg LW/d or with saline (n = 10). Jugular blood samples were taken once daily on Days - 1, 4, and 5 of treatment. bGH treatment in lambs up to Day 63 of life had little effect on plasma concentrations of GH, insulin, glucose or urea, but significantly (P < 0.05) increased circulating concentrations of IGF-I at all ages and of NEFA at Day 62/63 of life. In contrast, bGH treatment at either dose in yearlings significantly increased these parameters, except for plasma urea concentrations which were decreased in bGH-treated yearlings. However, the responses of plasma IGF-I concentration to bGH stimulus in lambs up to Day 63 of life were small compared to those in yearling sheep. Consistent with this, bGH treatment failed to affect hepatic GH binding in young lambs, but up-regulated it in yearling sheep. Furthermore, basal (unstimulated) GH binding did not differ between sheep of 7 vs. 63 vs. 365 d of age, despite the greater IGF-I responses to bGH in the latter group. It is suggested that hepatic GHR in lambs up to Day 63 of life are not fully functional compared to the situation in yearlings.     

Antepartal insulin-like growth factor concentrations indicating differences in the metabolic adaptive capacity of dairy cows

Cows with different Insulin-like Growth Factor-I (IGF-I) concentrations showed comparable expression levels of hepatic growth hormone receptor (GHR). Suppressor of cytokine signaling 2 (SOCS2), could be responsible for additional inhibition of the GHR signal cascade. The aims were to monitor cows with high or low antepartal IGF-I concentrations (IGF-I^high or IGF-I^low), evaluate the interrelationships of endocrine endpoints, and measure hepatic SOCS2 expression. Dairy cows (n = 20) were selected (240 to 254 days after artificial insemination (AI)). Blood samples were drawn daily (day -17 until calving) and IGF-I, GH, insulin, thyroid hormones, estradiol, and progesterone concentrations were measured. Liver biopsies were taken (day 264 ± 1 after AI and postpartum) to measure mRNA expression (IGF-I, IGFBP-2, IGFBP-3, IGFBP-4, acid labile subunit (ALS), SOCS2, deiodinase1, GHR1A). IGF-I concentrations in the two groups were different (p < 0.0001). However, GH concentrations and GHR1A mRNA expression were comparable (p > 0.05). Thyroxine levels and ALS expression were higher in the IGF-I^high cows compared to IGF-I^low cows. Estradiol concentration tended to be greater in the IGF-I^low group (p = 0.06). It was hypothesized that low IGF-I levels are associated with enhanced SOCS2 expression although this could not be decisively confirmed by the present study.     

Effect of photoperiod on hepatic growth hormone receptor 1A expression in steer calves

Photoperiod manipulation, specifically a long-day photoperiod (LDPP), increases milk production in lactating cattle. We have previously reported that the galactopoietic effect of LDPP is associated with an increase in circulating IGF-I, which seems to occur independently of changes in concentrations of GH, IGFBP-2, and IGFBP-3. This study tested the hypothesis that LDPP increases the expression of GH receptor (GHR) 1A messenger RNA (mRNA) in the liver. Two groups of Holstein steer calves (98 +/- 4 d old) were maintained indoors and exposed to LDPP (16-h light: 8-h dark; n = 6) or short-day photoperiod (SDPP; 8-h light: 16-h dark; n = 6) for 60 d. Calves were individually fed a grain- and alfalfa-based diet. Jugular blood samples were collected weekly and via cannula at 15-min intervals for a 4-h period on d 1, 26, and 55 of the study to monitor pulsatile hormone secretion. Serum was harvested and assayed for IGF-I, prolactin (PRL), and GH using RIA. Liver biopsies were obtained at 3-wk intervals to quantify changes in hepatic IGF-I and GHR 1A mRNA using real-time PCR. Steer BW increased during the study but did not differ between treatments. No differences in ADG or total DMI were observed. Relative to SDPP, calves on LDPP had higher (P < 0.05) serum IGF-I concentrations. Concentrations of PRL increased (P < 0.01) in calves exposed to LDPP compared with calves exposed to SDPP. Differences (P < 0.05) in pulsatile GH secretion were also detected. Hepatic IGF-I and GHR 1A mRNA were positively correlated with circulating IGF-I concentrations, and although both increased with time, they were not affected by photoperiod treatment. These results confirm that LDPP increases circulating concentrations of IGF-I, but this occurs independently of changes in IGF-I synthesis and GHR 1A mRNA expression in the liver. Therefore, our hypothesis that LDPP increases the expression of GHR 1A mRNA in the bovine liver is rejected.     

Influence of nutritional deprivation on insulin-like growth factor I, somatotropin, and metabolic hormones in swine

Although growth hormone (GH) is a primary stimulus for the synthesis of insulin-like growth factor I (IGF-I), other factors such as nutritional status, insulin, and thyroid hormones are important modulators of circulating IGF-I levels. Thus, the effects of feed restriction and subsequent refeeding on plasma levels of IGF-I, GH, insulin, and thyroid hormones were studied in swine. Despite an elevation in plasma GH levels after 48 h of feed restriction, circulating IGF-I levels were decreased by 53% (P less than .05). Plasma triiodothyronine (T3) and insulin were lower (P less than .05) within 24 h after the feed restriction began, whereas thyroxine (T4) did not decrease until 48 h after removal of feed. Blood glucose levels remained unchanged throughout the experiment. Refeeding after the 48-h fast was associated with a decline (P less than .05) in circulating GH levels within 2 h, concomitant with an elevation (P less than .05) in plasma insulin and T3. Refeeding fasted pigs was associated with an increase (P less than .05) in plasma IGF-I; however, levels still had not returned to prefast concentrations within 24 h after refeeding. These data indicate that the GH-IGF-I axis becomes uncoupled during nutritional restriction in swine and that inadequate nutrient supply may limit the expression of the anabolic effects of GH.     

Effect of growth hormone administration to mature miniature Brahman cattle treated with or without insulin on circulating concentrations of insulin-like growth factor-I and other metabolic hormones and metabolites

Previously, we determined that a primary cause of proportional stunted growth in a line of Brahman cattle was related to an apparent refractoriness in metabolic response to GH in young animals. The objective of this study was to determine the effect of administration of GH, insulin (INS), and GH plus INS to mature miniature Brahman cows (n = 6; 9.7 ± 2.06 y; 391 ± 48.6 kg) and bulls (n = 8; 9.4 ± 2.00 y; 441 ± 54.0 kg) on circulating concentrations of metabolic hormones and metabolites, primarily IGF-I and IGF-I binding proteins. We hypothesized that IGF-I secretion could be enhanced by concomitant administration of exogenous GH and INS, and neither alone would be effective. Animals were allotted to a modified crossover design that included four treatments: control (CON), GH, INS, and GH + INS. At the start of the study, one-half of the cattle were administered GH (Posilac; 14-d slow release) and the other one-half served as CON for 7 d. Beginning on day 8, and for 7 d, INS (Novolin L) was administered (0.125 IU/kg BW) twice daily (7:00 AM and 7:00 PM) to all animals; hence, the INS and GH + INS treatments. Cattle were rested for 14 d and then were switched to the reciprocal crossover treatments. Blood samples were collected at 12-hour intervals during the study. Compared with CON, GH treatment increased (P < 0.01) mean plasma concentrations of GH (11.1 vs 15.7 ± 0.94 ng/mL), INS (0.48 vs 1.00 ± 0.081 ng/mL), IGF-I (191.3 vs 319.3 ± 29.59 ng/mL), and glucose (73.9 vs 83.4 ± 2.12 mg/dL) but decreased (P < 0.05) plasma urea nitrogen (14.2 vs 11.5 ± 0.75 mg/dL). Compared with INS, GH + INS treatment increased (P < 0.05) mean plasma concentration of INS (0.71 vs 0.96 ± 0.081 ng/mL), IGF-I (228.7 vs 392.3 ± 29.74 ng/mL), and glucose (48.1 vs 66.7 ± 2.12 mg/dL), decreased (P < 0.01) plasma urea nitrogen (13.6 vs 10.4 ± 0.76 mg/dL), and did not affect GH (13.5 vs 12.7 ± 0.95 ng/mL). In the miniature Brahman model, both the GH and GH + INS treatments dramatically increased circulating concentrations of IGF-I in mature cattle, suggesting that this line of Brahman cattle is capable of responding to bioactive GH.     

Metabolic adaptations associated with irreversible glucose loss are different to those observed during under-nutrition

In this study the hypothesis that irreversible glucose loss results in an 'uncoupling' of the somatotrophic axis (increasing plasma GH levels and decreasing plasma IGF-I) was tested. During periods of negative energy balance the somatotrophic axis respond by increasing plasma GH and decreasing plasma IGF-I levels. In turn, elevated GH repartitions nutrient by increasing lipolysis and protein synthesis, and decreases protein degradation. Irreversible glucose loss was induced using sub-cutaneous injections of phloridizin. Seven non-lactating cows were treated with 8g/day phloridizin (PHZ) and seven control animals (CTRL, 0g/day), while being restricted to a diet of 80% maintenance. PHZ treatment increased urinary glucose excretion (P<0.001), resulting in hypoglycemia (P<0.001). As a response to this glucose loss, the PHZ treated animals had elevated plasma NEFA (P<0.005) and BHBA (P<0.001) levels. Average plasma insulin concentrations were not altered with PHZ treatment (P=0.059). Plasma GH was not different between the two groups (P>0.1), whereas plasma IGF-I levels decreased significantly (P<0.001) with PHZ treatment. The decline in plasma IGF-I concentrations was mirrored by a decrease in the abundance of hepatic IGF-I mRNA (P=0.005), in addition the abundance of hepatic mRNA for both growth hormone receptors (GHR(tot) and GHR(1A)) was also decreased (P<0.05). Therefore, the irreversible glucose loss resulted in a partial 'uncoupling' of the somatotrophic axis, as no increase in plasma GH levels occurred although plasma IGF-I levels, hepatic IGF-I mRNA declined, and the abundance of liver GH receptor mRNA declined.     

Plasma concentrations of growth hormone and insulin-like growth factor-I in prepuberal quarter horses and ponies

The hypotheses were tested that among types of horses with phenotypically different mature sizes, a difference in pattern of secretion of 1) GH and 2) insulin-like growth factor-I (IGF-I) would exist prepuberally. To test these hypotheses, plasma was collected each 20 min for 8 hr from three types of horses [Quarter Horses (n=5), ponies (n=4), and Quarter Horse-pony F₁ crosses (n=5)] at 2, 4, and 10 months of age. Plasma concentrations of GH and IGF-I were determined by RIA and the patterns of secretion were quantified. Type of horse had no effect on tonic patterns of secretion of GH (P=0.92) or IGF-I (P=0.39), so the hypotheses were rejected and the data were pooled across types within age. Mean plasma concentrations of GH did not differ (P=0.74) with respect to age of horse. In contrast, number of pulses of GH per 8 hour (2 months = 2.3±0.4; 4 months = 2.2±0.5; 10 months = 2.8±0.9) and the interval between pulses (2 months = 87.1±23.1; 4 months = 121.7±25; 10 months = 111.5±15 min) changed quadratically (P=0.03 and P=0.02). Plasma concentrations of IGF-I decreased quadratically (P=0.01) from 2 months through 10 months of age. These data provide evidence to suggest that tonic secretion of GH and IGF-I may differ among prepuberal Quarter Horses and ponies with respect to age of horse but not type of horse.     

Relationships between plasma concentrations of leptin and other metabolic hormones in GH-transgenic sheep infused with glucose

To study the regulation of leptin secretion in sheep, we infused glucose (0.32 g/h/kg for 12 h) into GH-transgenic animals (n = 8) that have chronically high plasma concentrations of ovine GH and insulin, but low body condition and low plasma leptin concentrations, and compared the responses with those in controls (n = 8). In both groups, the infusion increased plasma concentrations of glucose and insulin within 1 h and maintained high levels throughout the infusion period (P < 0.0001). Compared with controls, GH-transgenics had higher concentrations of insulin, IGF-1, GH (all P < 0.0001) and cortisol (P < 0.05), but lower GH pulse frequency (P < 0.0001). Overall, leptin concentrations were lower in GH-transgenics than in controls (P < 0.01). A postprandial increase in leptin concentrations was observed in both groups, independently of glucose treatment, after which the values remained elevated in animals infused with glucose, but returned to basal levels in those infused with saline, independently of transgene status. In both GH-transgenics and controls, glucose infusion did not affect the concentrations of GH, IGF-1, or cortisol. In conclusion, GH-transgenic and control sheep show similar responses to glucose infusion for leptin and other metabolic hormones, despite differences between them in body condition and basal levels of these hormones. Glucose, insulin, GH, IGF-1 and cortisol are probably not major factors in the acute control of leptin secretion in sheep, although sustained high concentrations of GH and IGF-1 might reduce adipose tissue mass or inhibit leptin gene expression.     

Serum leptin concentrations, luteinizing hormone and growth hormone secretion during feed and metabolic fuel restriction in the prepuberal gilt

Two experiments were conducted to determine 1) the effect of acute feed deprivation on leptin secretion and 2) if the effect of metabolic fuel restriction on LH and GH secretion is associated with changes in serum leptin concentrations. Experiment (EXP) I, seven crossbred prepuberal gilts, 66 +/- 1 kg body weight (BW) and 130 d of age were used. All pigs were fed ad libitum. On the day of the EXP, feed was removed from four of the pigs at 0800 (time = 0) and pigs remained without feed for 28 hr. Blood samples were collected every 10 min from zero to 4 hr = Period (P) 1, 12 to 16 hr = P 2, and 24 to 28 hr = P 3 after feed removal. At hr 28 fasted animals were presented with feed and blood samples collected for an additional 2 hr = P 4. EXP II, gilts, averaging 140 d of age (n = 15) and which had been ovariectomized, were individually penned in an environmentally controlled building and exposed to a constant ambient temperature of 22 C and 12:12 hr light: dark photoperiod. Pigs were fed daily at 0700 hr. Gilts were randomly assigned to the following treatments: saline (S, n = 7), 100 (n = 4), or 300 (n = 4) mg/kg BW of 2-deoxy-D-glucose (2DG), a competitive inhibitor of glycolysis, in saline iv. Blood samples were collected every 15 min for 2 hr before and 5 hr after treatment. Blood samples from EXP I and II were assayed for LH, GH and leptin by RIA. Selected samples were quantified for glucose, insulin and free fatty acids (FFA). In EXP I, fasting reduced (P < 0.04) leptin pulse frequency by P 3. Plasma glucose concentrations were reduced (P < 0.02) throughout the fast compared to fed animals, where as serum insulin concentrations did not decrease (P < 0.02) until P 3. Serum FFA concentrations increased (P < 0.02) by P 2 and remained elevated. Subcutaneous back fat thickness was similar among pigs. Serum IGF-I concentration decreased (P < 0.01) by P 2 in fasted animals compared to fed animals and remained lower through periods 3 and 4. Serum LH and GH concentrations were not effected by fast. Realimentation resulted in a marked increase in serum glucose (P < 0.02), insulin (P < 0.02), serum GH (P < 0.01) concentrations and leptin pulse frequency (P < 0.01). EXP II treatment did not alter serum insulin levels but increased (P < 0.01) plasma glucose concentrations in the 300 mg 2DG group. Serum leptin concentrations were 4.0 +/- 0.1, 2.8 +/- 0.2, and 4.9 +/- 0.2 ng/ml for S, 100 and 300 mg 2DG pigs respectively, prior to treatment and remained unchanged following treatment. Serum IGF-I concentrations were not effected by treatment. The 300 mg dose of 2DG increased (P < 0.0001) mean GH concentrations (2.0 +/- 0.2 ng/ml) compared to S (0.8 +/- 0.2 ng/ml) and 100 mg 2DG (0.7 +/- 0.2 ng/ml). Frequency and amplitude of GH pulses were unaffected. However, number of LH pulses/5 hr were decreased (P < 0.01) by the 300 mg dose of 2DG (1.8 +/- 0.5) compared to S (4.0 +/- 0.4) and the 100 mg dose of 2DG (4.5 +/- 0.5). Mean serum LH concentrations and amplitude of LH pulses were unaffected. These results suggest that acute effects of energy deprivation on LH and GH secretion are independent of changes in serum leptin concentrations.     

Luteinizing hormone,growth hormone,insulin-like growth factor-i,insulin and metabolites before puberty in heifers fed to gain at two rates

Fall born Angus x Hereford heifers were allotted to treatments at 9 mo of age to achieve the following growth rates: 1) fed to gain 1.36 kg/d (n = 10; HGAIN); and 2) fed to gain 0.23 kg/d for 16 wk, then fed to gain 1.36 kg/d (n = 9; LHGAIN). Growth hormone (GH), insulin-like growth factor-1 (IGF-I), insulin, glucose, nonesterified fatty acids (NEFA), and progesterone were quantified in twice weekly blood samples until onset of puberty. Body weight, hip height, and pelvic area were recorded every 28 d. Frequent blood samples (n = 8 heifers/treatment) were collected every 14 d, commencing on day 29 of treatment until onset of puberty to evaluate secretion of luteinizing hormone (LH) and GH. The HGAIN heifers were younger (369 d; P < 0.001), were shorter at the hip (115 cm; P < 0.05) and had smaller pelvic area (140 cm²; P < 0.10), but body weight (321 kg) did not differ at puberty compared with LHGAIN heifers (460 d; 119 cm; 155 cm²; 347 kg, respectively). The HGAIN heifers had greater (P < 0.05) concentrations of LH, IGF-I, and insulin in serum and glucose in plasma during the first 84 d of treatment than LHGAIN heifers, whereas LHGAIN heifers had greater (P < 0.05) concentrations of GH in serum and NEFA in plasma than HGAIN heifers. On Day 68 of treatment, HGAIN heifers had less mean GH (P < 0.01) and greater (P < 0.05) LH pulse frequency than LHGAIN heifers, whereas LH pulse amplitude and mean LH did not differ (P > 0.10) between treatments. Treatment did not influence secretion of LH and GH at 1 and 3 wk before puberty. Mean GH concentrations in serum and GH pulse amplitude in all heifers were greater (P < 0.05) 2 to 9 d (12.9 and 40.7 ng/ml, respectively) than 16 to 23 d (10.4 and 20.0 ng/ml, respectively) before puberty. Nutrient restriction decreased LH pulse frequency and delayed puberty in beef heifers. Furthermore, dramatic changes in mean concentration and amplitude of GH pulses just before puberty in beef heifers may have a role in pubertal development.     

The effect of dietary energy source on serum concentration of insulin-like growth factor-I growth hormone,insulin, glucose,and fat metabolites in weanling horses

Feeding diets high in soluble carbohydrates to growing horses has been implicated in the development of orthopedic diseases; as a result, substitution of dietary fat for soluble carbohydrates has received attention. Because IGF-I is integral to growth and cartilage development and because it is influenced by nutrition, we evaluated the effect of dietary fat substitution on metabolic endpoints and circulating GH and IGF-I in growing horses. Twelve Quarter Horse weanlings, four female and eight male, 151 to 226 d old, were blocked by sex and age and assigned to two treatment groups. Group one (CARB; n = six) was fed a concentrate containing 2.21% fat and 33.9% starch; group two (FAT; n = six) was fed a concentrate containing 10.3% fat and 24.0% starch. Both concentrates contained 3.0 Mcal/kg of DE and 16% CP. Brome hay also was fed. Diets were fed at 0800 and 1600 for 60 d. On d 0, 30, and 60, blood samples were obtained via a jugular catheter from 1 h before until 5 h after the morning feeding. Serum was analyzed for glucose, insulin, GH, IGF-I, NEFA, and total cholesterol (CHOL). Neither ADG (0.85 +/- 0.04 and 0.84 +/- 0.04 kg) nor concentrate DMI (4.04 +/- 0.12 and 4.03 +/- 0.12 kg/d) differed between treatments. There were consistent increases in glucose and insulin in response to feeding on d 0, 30, and 60 for both groups. On d 30, the glucose response to feeding was less (P = 0.07) over time in FAT vs. CARB; however, there were no significant treatment x time effects on d 0 or 60. On d 60, the insulin response to feeding was less (P < 0.05) over time in FAT compared with CARB; however, there was no treatment x time effect on d 0 or 30. Serum CHOL concentrations did not differ between groups on d 0. Horses in the FAT group had increased CHOL concentrations on d 30 and 60 compared with CARB (P < 0.01). Although treatment x time interactions were noted for GH on d 30 and 60 (P < 0.05), only transient and inconsistent differences in the secretory profiles between CARB and FAT treatments were evident at those sampling times. Serum NEFA and IGF-I did not differ between treatments on d 0, 30, or 60. These results suggest that dietary energy source, at least at the level used in this study, did not affect foal growth performance or serum IGF-I and NEFA concentrations. Fat substitution increased serum CHOL and variably affected serum GH, glucose, and insulin concentrations in response to feeding.     

Effect of nutrient intake on the development of the somatotropic axis and its responsiveness to GH in Holstein bull calves

We investigated the effect of increasing nutrient intake on the responsiveness of the GH/IGF-I system in calves fed a high-protein milk replacer. Fifty-four Holstein bull calves were fed one of three levels (low, medium, and high; n = 18 per treatment) of a 30% crude protein, 20% fat milk replacer to achieve target rates of gain of 0.50, 0.95, or 1.40 kg/d, respectively, for low, medium, and high. Six calves per treatment were slaughtered at approximately 65, 85, and 105 kg BW. Additionally, six calves were slaughtered at 1 d of age to provide baseline data. Plasma aliquots from blood samples collected weekly were analyzed for IGF-I, insulin, glucose, NEFA, and plasma urea nitrogen (PUN). Plasma IGF-I and insulin, measured weekly, increased (P < 0.001) with greater nutrient intake from wk 2 of life to slaughter. Plasma glucose and NEFA also increased (P < 0.05) with nutrient intake. In addition, each calf underwent a GH challenge beginning 4 d before the scheduled slaughter. Plasma from blood collected before the first GH injection and 14 and 24 h after the third injection was analyzed for IGF-I and PUN. Response to challenge, calculated as the absolute difference between the prechallenge and 14-h postchallenge plasma IGF-I concentrations, was significant in calves on all three treatments. Plasma urea nitrogen was not different among treatments as measured weekly but decreased (P < 0.001) following GH challenge in all calves. Results of ribonuclease protection assays showed increased expression of hepatic mRNA for GH receptor 1A and IGF-I with increased intake. The amounts of GH receptor and IGF-I mRNA in muscle and adipose, however, were not affected by intake. In summary, plasma IGF-I was elevated in calves with increased nutrient intake, and the elevations in plasma IGF-I following short-term administration of GH were significant in all calves by 65 kg BW. Data demonstrate that in well-managed milk-fed calves the somatotropic (GH/IGF-I) axis is functionally coordinated and sensitive to nutrient intake and GH.     

Effects of body condition score at parturition and postpartum supplemental fat on metabolite and hormone concentrations of beef cows and their suckling calves

To determine the effects of BCS at parturition and postpartum lipid supplementation on blood metabolite and hormone concentrations, 3-yr-old Angus x Gelbvieh beef cows, which were nutritionally managed to achieve a BCS of 4 +/- 0.07 (479.3 +/- 36.3 kg of BW) or 6 +/- 0.07 (579.6 +/- 53.1 kg of BW) at parturition, were used in a 2-yr experiment (n = 36/yr). Beginning at 3 d postpartum, cows within each BCS were assigned randomly to be fed hay and a low-fat control supplement or lipid supplements with either cracked high-linoleate or high-oleate safflower seeds until d 61 of lactation. The diets were formulated to be isonitrogenous and isocaloric, and the safflower seed supplements were formulated to achieve 5% DMI as fat. On d 31 and 61 of lactation, blood samples were collected preprandially and then hourly postprandially (at 0, 1, 2, 3, and 4 h). Serum insulin (P = 0.27) and glucose (P = 0.64) were not affected by BCS at parturition. The mean concentrations of plasma NEFA (P = 0.08) and beta-hydroxybutyrate (P = 0.08) tended to be greater, and serum IGF-I was greater (P < 0.001) in BCS 6 than BCS 4 cows. Conversely, serum GH was greater (P = 0.003) for BCS 4 cows, indicating that regulation of IGF by GH may have been uncoupled in BCS 4 cows. The postpartum diet did not affect NEFA (P = 0.94), glucose (P = 0.15), IGF-I (P = 0.33), or GH (P = 0.62) concentrations. Oleate-supplemented cows had greater (P = 0.03) serum insulin concentrations, whereas control cows had greater (P = 0.01) plasma beta-hydroxybutyrate concentrations. Concentrations of NEFA (P = 0.05) and glucose (P < 0.001) were greater, and beta-hydroxybutyrate tended (P = 0.07), to be greater at d 3, whereas serum IGF-I was greater (P = 0.003) at d 6 of lactation. Similar concentrations of NEFA, glucose, GH, and IGF-I indicate that the nutritional status of beef cows during early lactation was not influenced by lipid supplementation. However, perturbations of the somatotropic axis in BCS 4 cows indicate that the influence of energy balance and BCS of the cow at parturition on postpartum performance should be considered when making managerial decisions.     

Effects of growth hormone and gonadotrophin releasing hormone antagonists on ovarian follicle growth in sheep

Our objective was to determine the effects of the administration of growth hormone (GH) alone or plus teverelix, a gonadotrophin releasing hormone antagonist (GnRHa), on follicle development in sheep. Ewes were treated daily for 6 days by the intramuscular route with 15 mg of GH alone (GH group; n = 6) or combined with two subcutaneous doses of GnRHa (1.5 mg) on days 0 and 3 of GH treatment (GH/GnRHa group; n = 6); the control group (n = 6) received similar treatment with saline solution. Plasma follicle stimulating hormone levels were significantly lower in the GH/GnRHa group than in the control (P < 0.001) and GH groups (P < 0.05). The number of follicles > or =2 mm increased to reach significant differences with control (18.7 +/- 0.6) on day 4 in GH/GnRHa group (22.7 +/- 0.5, P < 0.001) and on day 5 in GH group (20.3 +/- 0.4 vs. 17.0 +/- 0.6, P < 0.05). These results indicate that GH and GnRHa may be useful for increasing the number of gonadotrophin-responsive follicles in the ovary. However, follicle function could be affected as both GH and GH/GnRHa groups showed lower plasma inhibin A concentrations than control sheep (90-110 pg/mL vs. 170-185 pg/mL, P < 0.005).     

Effect of exogenous estradiol on plasma concentrations of somatotropin, insulin-like growth factor-I, insulin-like growth factor binding protein activity, and metabolites in ovariectomized angus and braham cows

To determine the effect of breed and estradiol-17β on selected hormones and metabolites, ovariectomized (3 mo) Angus (n = 14) and Brahman (n = 12) cows were paired by age and body weight and randomly assigned as either nonimplanted controls (CON) or implanted with estradiol (E2) for 45 d. After Day 7 and through Day 42, plasma concentration of somatotropin was greater for E2 than CON cows (treatment X day, P < 0.05). During an intensive blood sampling on Day 36, E2 cows tended (P < 0.10) to have greater somatotropin pulse amplitudes than CON cows, but other parameters of somatotropin release were not affected (P > 0.10) by E2 treatment. The effect of breed was apparent on Day 36 as Brahman cows had greater (P < 0.05) somatotropin pulse amplitude, basal secretion, and mean concentration than Angus cows. Overall, plasma concentration of IGF-I was greater (P < 0.01) for E2 than CON cows (158.3 vs. 104.2 ng/ml) and was greater for Brahman than Angus cows (164.1 vs. 98.4 ng/ml). However, there was a trend (P < 0.10) for a treatment X breed X day interaction for IGF-I (i.e., the magnitude of increase in IGF-I concentration was greater in E2-Angus than E2-Brahman cows). After Day 7 and through Day 42, total plasma IGF binding protein (IGFBP) activity was greater (P < 0.01) for E2 than CON cows. Ligand blotting revealed at least five forms of IGFBP activity, and E2 cows had greater (P < 0.05) binding activity of IGFBP-3 and the 30- and 32-kDa IGFBP than CON cows. Brahman cows had greater (P < 0.05) IGFBP-3 and the 32-kDa IGFBP than Angus cows. After Day 14 and through Day 42, concentration of urea nitrogen (PUN) was greater (P < 0.001) for CON than E2 cows (treatment X day, P < 0.001). Brahman had greater (P < 0.01) PUN than Angus cows (16.6 vs. 14.2 mg/dl). Plasma concentration of glucose was greater (P < 0.01) for E2 than CON cows (78.9 vs. 76.4 mg/dl) but was not affected (P > 0.10) by breed. In summary, these data suggest that some, but not all, of the positive effects of estradiol on peripheral concentration of IGF-I and IGFBP activity can be attributed to increased somatotropin. Moreover, breed influenced basal and E2-induced secretion of somatotropin and IGF-I such that differences between Brahman and Angus cows in plasma IGF-I concentrations were abated within 3 wk of estradiol implantation. Thus, breed influences the metabolite and hormonal response of cattle to estrogenic implants.     

Abundance of message for insulin-like growth factors-I and -II and for receptors for growth hormone,insulin-like growth factors-I and -II,and insulin in the intestine and liver of pre- and full-term calves

The somatotropic axis and insulin are involved in pre- and postnatal development. In pre- and full-term calves (GrP0 and GrN0; born after 277 and 290 d of pregnancy, respectively) and in preterm calves on d 8 of life after being fed for 7 d (GrP8), we studied whether there are differences in the abundance of messenger RNA (mRNA) of IGF-I and IGF-II and of receptors for GH, IGF-I, IGF-II, and insulin among different intestinal sites (duodenum, jejunum, ileum, and colon) and whether there are ontogenetic differences during the perinatal period in intestine and liver. Intestinal site differences (P < 0.05) existed in mRNA levels of IGF-I and IGF-II and receptors for GH, IGF-I, IGF-II, and insulin. Abundance of mRNA of IGF-I and -II and of receptors for IGF-I and GH was highest (P < 0.05) in the colon, abundance of the receptor for IGF-II was comparably high in the colon and ileum, and that of the receptor for insulin was similarly high in colon, ileum, and jejunum. Among GrP0, GrN0, and GrP8 groups, there were differences (P < 0.05) in mRNA levels of IGF-I and IGF-II and of receptors for GH, IGF-I, IGF-II and insulin. Abundance of mRNA of IGF-I and IGF-II and of receptors for GH, IGF-I, IGF-II and insulin was highest (P < 0.05) in GrP0 calves immediately after birth and was primarily seen in the ileum. In liver, the mRNA levels differed (P < 0.05) among groups for IGF-II and receptors for IGF-I, IGF-II, and insulin, and were highest (P < 0.05) for IGF-II in GrP0, for receptors of IGF-I in GrN0, and were higher (P < 0.05) in GrP0 than GrP8 for receptors of IGF-II. In conclusion, mRNA levels of IGF-I and IGF-II and of receptors for GH, IGF-I, IGF-II, and insulin were different at different intestinal sites and in intestine and liver and changed during the perinatal period.     

Effects of low feed intake and hot environment on plasma profiles of glucose, nonesterified fatty acids, insulin, glucagon, and IGF-I in lactating sows

This experiment was designed to compare the effects of high ambient temperature and of feed restriction on plasma hormones and metabolites in primiparous lactating sows. Females were exposed to a constant thermoneutral (20 degrees C) or hot environment (30 degrees C) during lactation. Sows housed at 30 degrees C were given free access to feed (30AL: n = 12), whereas those housed at 20 degrees C were either pair-fed with those at 30 degrees C (20RF: n = 6) or were fed ad libitum (20AL: n = 6). A jugular vein catheter was surgically inserted in all sows at 100 d of gestation. Absorption of nutrients during the meal induced significant increases in plasma glucose, insulin, and glucagon, and a decrease in nonesterified fatty acids on Day 19 of lactation and Day 1 postweaning (P < 0.05). On Day 19, feed restriction at 20 degrees C was associated with higher plasma glucagon before the meal, lower plasma insulin after the meal and a lower insulin-to-glucagon ratio (I/GA) before and after the meal (P < 0.05). On Day 19, mean plasma concentrations measured in 30AL females were between those measured in 20AL and 20RF sows for nonesterified fatty acids and glucagon before feeding, and for glucose, nonesterified fatty acids, insulin, and glucagon after feeding. None of the differences between the 30AL and the 20RF groups was significant (P < 0.1). On Day 19, the only significant differences between the 30AL and 20AL groups were observed after the meal for plasma insulin and I/GA. Plasma insulin-like growth factor-I increased after farrowing in 20AL and 30AL sows only (P < 0.05). It was higher in 20AL than in 20RF and 30AL sows on Days 4 and 19 of lactation (P < 0.05). Overall, underfeeding at 20 degrees C induced changes in plasma insulin, glucagon, I/GA, and insulin-like growth factor-I, which would favor gluconeogenesis and body-reserve mobilization during lactation. Differences in glucagon and I/GA before the meal between well-fed sows at 20 degrees C and heat-exposed sows were attenuated, which could have detrimental consequences on glucose availability to the mammary gland and hence on milk production at 30 degrees C.