Somatotropin Treatment Research Articles

Perioperative Management in Rothmund–Thomson Syndrome

Rothmund-Thomson Syndrome (RTS) is a rare, multisystem disease accompanied by many anomalies that require careful attention from preoperative evaluation to discharge regarding anesthesia preparation and management. Due to craniofacial deformities accompanying facial abnormalities, maintaining the airway becomes a complete struggle with a race against time for survival. This case report presents the preoperative preparation and perioperative management, the risks that may be encountered, and the detailed preparation for a 7-year-old patient diagnosed with RTS and multiple system involvement. General anesthesia was administered to this patient, who had intrauterine growth retardation, nail streaking, redness of the bullae and legs, and a history of somatotropin treatment and antinuclear antibody (ANA) positivity under optimum conditions. Thanks to successful and detailed preoperative preparation and perioperative management, the patient was followed up and discharged without any complications. Although RTS is rare, the need for general anesthesia often arises due to juvenile cataracts, dental anomalies, syndactyly and other extremity anomalies in these patients whose airway management is complex. Furthermore, this increases the current risk in the population of these patients. Managing these patients with a multidisciplinary approach will reduce complications, morbidity, mortality, and length of stay.

Correlation of Bovine Dairy Igf-1 And the Neoplasia Development

Cow's milk and its derivatives are among the most consumed foods in the world being part of the daily diet of several people. However, its consumption is linked to factors that were associated with neoplastic development, such as IGF-1. IGF-1 acts by stimulating growth effects on most cells of the body via the IGF1R receptor. In this context, this work aimed to investigate studies that correlate these variables: IGF-1, cow's milk, and neoplasias. The results showed that IGF-1 in cow's milk may increase serum IGF-1 levels in humans from milk consumption. Also, we have shown it that some supplements such as choline and casein do not alter the amount of IGF-1, but when the cow undergoes recombinant bovine somatotropin treatment, there is a significant increase in circulating IGF-1. However, further studies are needed to explain the cause-and-effect relationship noted in this study.

The Association between Somatotropin Therapy and the Risk of SARS-CoV-2 Infection in Children with Short Stature: A Population-Based Cross-Sectional Study.

COVID-19 is a worldwide pandemic caused by SARS-CoV-2, to which adults are usually more susceptible than children. Growth hormone (GH) levels differ between children and adults and decrease with age. There is bidirectional crosstalk between the GH/insulin-like growth factor-1 (IGF-1) pathway and the immune system that plays a significant role in SARS-CoV-2 infection. We evaluated the association between somatotropin treatment (GH replacement therapy) and the risk for SARS-CoV-2 positivity (a marker for COVID-19 infection) in children with growth hormone issues (GHI): growth hormone deficiency (GHD) and idiopathic short stature (ISS). A population-based cross-sectional study in Leumit Health Services (LHS) was performed using the electronic health record (EHR) database. The rates of SARS-CoV-2 positivity were evaluated among children with GHI, treated or untreated with somatotropin. Higher rates of SARS-CoV-2 positivity were found in GHI children, influenced by the same confounders reported in the pediatric population. A lower prevalence of SARS-CoV-2 PCR positivity was found among the somatotropin-treated children. A multivariate analysis documented that somatotropin treatment was associated with a reduced risk of SARS-CoV-2 positivity (Odds Ratio (OR) = 0.47, Confidence Interval (CI) 0.24-0.94, p = 0.032). Thus, somatotropin might be a protective factor against SARS-CoV-2 infections, possibly related to its immunomodulatory activity.

Impact of Recombinant Bovine Somatotropin on Bovine Milk Composition and Fatty Acidome: A Multidose Longitudinal Study.

Somatotropin is a species-specific polypeptide hormone produced in the pituitary gland of vertebrates. When administered exogenously to cattle, it can increase milk yield. However, the trade and administration of recombinant bovine somatotropin (rbST) to farm animals have been banned in the European Union (EU). Aside from food safety issues, very little is known about the effects of this hormone on milk composition and quality. In this work, a wide profile of fatty acids (the so-called fatty acidome) was determined by GC-FID in raw milk collected from control and rbST-treated lactating cows in a multidose longitudinal study. Milk composition (lactose, protein, fat, dry matter), including minerals (Ca, K, Mg, Na, P), was also determined, and milk yield was recorded. A tendency toward a less saturated profile was observed in the milk collected from animals treated with rbST, with higher concentrations of monounsaturated fatty acids. In addition, less calcium and potassium and more lactose and protein content were observed in milk from treated animals than in regular milk. As a result of this multicomponent profiling of milk, a clear impact of somatotropin treatment on milk quality was observed. The obtained results should be particularly interesting for those countries that permit the use of this hormone in dairy production.

Profitability of dairy cows submitted to the first service with the Presynch-Ovsynch or Double-Ovsynch protocol and different duration of the voluntary waiting period

The objective of this study was to compare cash flow and parameters of economic performance for dairy cows submitted to the first service using a combination of insemination at detected estrus and timed AI (TAI) in cows synchronized with the Presynch-Ovsynch (PSOv) protocol versus all TAI after synchronization of ovulation with the Double-Ovsynch (DO) protocol with different durations of the voluntary waiting period. A secondary objective was to calculate the variation in cash flow under different input pricing scenarios through stochastic Monte Carlo simulation. Lactating Holstein cows from a commercial dairy farm were randomly assigned to 3 first-service management programs. Cows in the PSOv treatment (n = 450) received first service through a combination of insemination at detected estrus after a voluntary waiting period of 50 d in milk (DIM; i.e., after second PGF2α treatment of the protocol) and TAI at 72 ± 3 DIM. Cows in the DO60 (n = 458) and DO88 (n = 462) treatments received first service by TAI at 60 ± 3 and 88 ± 3 DIM, respectively. Individual cow cash flow was calculated for the calving interval after enrollment and for an 18-mo period after calving. Cash flow was the aggregation of daily income over feed cost, replacement cost, calf value, recombinant bovine somatotropin treatment cost, reproductive cost, and other operating expenses. All analyses were conducted separately for primiparous and multiparous cows. Continuous, binomial, and time to event outcomes were analyzed using ANOVA, logistic regression, and Cox's proportional hazard regression in SAS (SAS Institute Inc., Cary, NC). Treatments affected the dynamics of pregnancy creation, which affected time to pregnancy during lactation. As a result, we observed differences in the proportion of nonpregnant cows at the end of lactation, herd exit dynamics, lactation length, calving interval, and proportion of cows that calved again. Some of these effects varied by parity, affecting the direction and magnitude of treatment differences within parity group. For primiparous cows, maximum cash flow differences per slot for the 18-mo period were in the range of $26 (PSOv > DO60) to $29 (DO88 > DO60) but did not differ statistically. For multiparous cows, maximum cash flow differences per slot for the 18-mo period were in the range of $122 (PSOv > DO88) to $155 (DO60 > DO88) but did not differ statistically. Despite the substantial differences in cash flow (in particular for multiparous cows) caused by the effect of treatments on reproductive performance, herd exit dynamics, and calving interval, large variability in overall cash flow among individual cows and compensation between multiple outcomes resulted in lack of statistical differences in cash flow. Outcomes from the stochastic analysis indicated that similar trends for differences between treatments would be observed under varying scenarios for economic input values. In conclusion, we did not detect statistically significant cash flow differences between the PSOv, DO60, and DO88 treatments, but numerical trends and stochastic simulation indicated that the DO88 and PSOv treatments were more economically favorable than the DO60 treatment for primiparous cows. For multiparous cows, the DO60 and PSOv treatments were more economically favorable than the DO88 treatment.

Effect of recombinant bovine somatotropin (rbST) treatment on follicular population and development in non-lactating dairy cows.

The aim of this study was to evaluate the long-term effects of recombinant bovine somatotropin (rbST) on follicle population and ovulatory follicle development in non-lactating dairy cows. Twenty-one Jersey cows were allocated in rbST (n=11) or control (n=10) groups. On day -60, cows in rbST group received 500 mg of somatotropin (s.c. Lactotropin®, Elanco). On day 0, control and rbST cows received an intravaginal progesterone-releasing device (1.9 g, CIDR®, Zoetis) and GnRH (100 mg, IM, Factrel®, Zoetis). On day 8, cows received PGF2α (25 mg, IM, Lutalyse®, Zoetis) and the CIDR® was removed. Twelve hours after device removal (D8), serum, follicular fluid and granulosa cells samples were collected. Serum and follicular concentration of estradiol (E2) and progesterone (P4) were analyzed. Total RNA was extracted from granulosa cells to measure gene expression of LHCGR, STAR, HSD-3B1, CYP11A1, CYP19A1, CYP17A1, IGFR and PAPPA by real-time PCR. Ultrasonography was performed on days -60, -53, -46, -14, -7, 0 and 8 for antral follicle count. Results were analyzed by repeated measures ANOVA and t-test. There was no effect of rbST treatment on the number of follicles during the 60 days period, as well as no effect on serum and follicular fluid E2 and follicular fluid P4 at the moment of follicle aspiration. There was a reduction in PAPPA (P = 0.006), CYP11A1 (P = 0.04) and CYP19A1 (P = 0.002) mRNA levels in granulosa cells of the pre-ovulatory follicle of rbST treated cows. In conclusion, a single dose of rbST did not have long-term effects on antral follicle population, serum and follicular E2/P4 concentrations in non-lactating dairy cows. Despite that, rbST injection decreased granulosa cell expression of genes related to steroidogenesis in the pre-ovulatory follicle.

Case Study: Effects of body weight gain and bovine somatotropin treatment of postpartum beef cows on concentrations of IGF-1, insulin, and glucose in blood plasma; luteal activity; and calf growth

ABSTRACT Angus × Hereford cows (2 and 3 yr of age, n = 37) were used to evaluate the effects of postpartum BW gain and treatment with bovine somatotropin (bST) on concentrations of IGF-I, glucose, and insulin in plasma during early lactation; luteal activity; and calf growth. Cows (456 ± 52 kg, BCS = 4.6 ± 0.4) were stratified based on calving date and BCS and randomly assigned to a 2 × 2 × 2 factorial: weight gain ≤0.4 kg/d (MWG) or >0.4 kg/d (HWG) during 24 to 59 d postpartum, injection with bST or saline (CON) on d 31 and 45 postpartum, and 2 or 3 yr of age. Concentrations of IGF-I in plasma before bST treatment were greater (P = 0.02) for HWG compared with MWG cows, and IGF-I was greater (P

Adherence to somatotropin treatment administered with an electronic device

IntroductionAdherence to somatotropin treatment is associated with increased growth velocity and improved adult height. The purpose of this study is to determine the adherence of patients undergoing treatment with an electronic device and its relationship with different variables (age, gender, duration of treatment, diagnosis, height, and growth rate). Material and methodsDescriptive, longitudinal and retrospective study of children less than 14 years of age undergoing treatment with somatotropin administered with the Easypod® electronic device in the Paediatric Endocrinology Outpatient Clinic of the General University Hospital of Ciudad Real, Spain. Adherence was monitored for 12 months and was defined according to the equation: (days administered at the prescribed dose/prescribed days)×100. The data analysis was performed using SPSS software. ResultsData were collected from 30 patients, with a predominance of males (57%), a mean age of 6.09 years, with 51% of children less than 5 years old. The most common reasons for the treatment were: small for gestational age (55%) and growth hormone deficiency (38%). The mean duration of treatment was 4.3 years (3.6–5). A mean adherence of 92.3% (87.7–96.9) was observed, and there was a significant correlation with age (Pearson R=−0.384, P=0.03), and duration of treatment (Pearson R=−0.537; P=0.003). ConclusionsThe adherence in our patients with electronic device is high (92.3%), and is inversely associated with age and duration. The use of electronic devices allows monitoring of therapeutic compliance, which affects the optimisation of treatment.

Adherencia al tratamiento con somatotropina administrada con dispositivo electrónico

IntroductionAdherence to somatotropin treatment is associated with increased growth velocity and improved adult height. The purpose of this study is to determine the adherence of patients undergoing treatment with an electronic device and its relationship with different variables (age, gender, duration of treatment, diagnosis, height, and growth rate). Material and methodsDescriptive, longitudinal and retrospective study of children less than 14 years of age undergoing treatment with somatotropin administered with the Easypod® electronic device in the Paediatric Endocrinology Outpatient Clinic of the General University Hospital of Ciudad Real, Spain. Adherence was monitored for 12 months and was defined according to the equation: (days administered at the prescribed dose / prescribed days)×100. The data analysis was performed using SPSS software. ResultsData were collected from 30 patients, with a predominance of males (57%), a mean age of 6.09 years, with 51% of children less than 5 years old. The most common reasons for the treatment were: small for gestational age (55%) and growth hormone deficiency (38%). The mean duration of treatment was 4.3 years (3.6-5). A mean adherence of 92.3% (87.7-96.9) was observed, and there was a significant correlation with age (Pearson R = -0.384, P=.03), and duration of treatment (Pearson R = -0.537; P=.003). ConclusionsThe adherence in our patients with electronic device is high (92.3%), and is inversely associated with age and duration. The use of electronic devices allows monitoring of therapeutic compliance, which affects the optimisation of treatment.

Cost-Effectiveness of Easypod™ Device Versus Other Somatotropin Delivery Techniques In Egypt In Treatment of Growth Hormone Deficiency

Normalization of height in childhood and adolescence with growth hormone deficiency (GHD) is possible via the use of the recombinant human growth hormone somatotropin. Different injection techniques were developed including easypod™ device, prefilled pens (PP), and the regular subcutaneous syringe (SCS). The aim of this study is to determine whether injecting somatotropin using easypod™ device is a cost-effective treatment option in Egyptian children born with GHD. A Markov decision-tree model was used to calculate the relative costs and health benefits associated with each delivery technique over the treatment period (treatment with somatotropin 0.025 mg/kg/day from ages 5 to 13 years) for a number of simulated children born with GHD using patients charts records data. A wastage model was developed to include the difference in wastage among the various techniques. Estimates of patient height were derived from published literature, as was the proportion of patients achieving normal height through somatotropin treatment. Health care resources and drug costs associated with each of the treatment arms were considered, and cost-effectiveness was estimated as discounted (3.5% per annum) Egyptian pounds (EGP) per centimeter-height (cmH) gained. Somatotropin delivery using easypod™ device was associated with an additional (5.15) cmH gained, at an incremental cost per cmH gained of (-13,021 EGP), compared with somatotropin PP. This means easypod™ device dominates. Versus delivery via SCS, easypod™ device resulted in additional (5.76) cmH gained at an incremental cost of (69,099 EGP). This equates to an incremental cost of (11,990 EGP) per cmH gained - below the widely accepted cost-effectiveness threshold in Egypt of (70,000 EGP). In this model, somatotropin delivery using easypod™ device was a cost-saving option compared with somatropin PP, and a cost-effective one if compared with somatropin SCS. The use of somatropin easypod™ device represents reasonable value for money for the treatment of GHD in Egyptian children.

Effect of hormonal and energy-related factors on plasma adiponectin in transition dairy cows

In transition dairy cows, plasma levels of the insulin-sensitizing hormone adiponectin fall to a nadir at parturition and recover in early lactation. The transition period is also characterized by rapid changes in metabolic and hormonal factors implicated in other species as positive regulators of adiponectin production (i.e., negative energy balance, lipid mobilization) and others as negative regulators (i.e., reduced leptin and insulin and increased growth hormone and plasma fatty acids). To assess the role of onset of negative energy balance and lipid mobilization after parturition, dairy cows were either milked thrice daily (lactating) or never milked (nonlactating) for up to 4 wk after parturition. Plasma adiponectin was 21% higher across time in nonlactating than lactating cows. Moreover, nonlactating cows recovered plasma adiponectin at similar rates as lactating cows even though they failed to lose body condition. Next, we assessed the ability of individual hormones to alter plasma adiponectin in transition dairy cows. In the first experiment, dairy cows received a constant 96-h intravenous infusion of either saline or recombinant human leptin starting on d 8 of lactation. In the second experiment, dairy cows were studied in late pregnancy (LP, starting on prepartum d -31) and again in early lactation (EL, starting on d 7 postpartum) during a 66-h period of basal sampling followed by 48 h of hyperinsulinemic-euglycemia. In the third experiment, cows were studied either in LP (starting on d -40 prepartum) or EL (starting on d 7 postpartum) during a 3-h period of basal sampling followed by 5 d of bovine somatotropin treatment. Plasma adiponectin was reduced by an average of 21% in EL relative to LP in these experiments, but neither leptin, insulin, or growth hormone treatment affected adiponectin in LP or EL. Finally, the possibility that plasma fatty acids repress plasma adiponectin was evaluated by intravenous infusion of a lipid emulsion in nonpregnant, nonlactating cows in the absence or presence of glucagon for 16 consecutive hours. The intralipid infusion increased plasma fatty acid concentration from 102 to over 570 µM within 3 h but had no effect on plasma adiponectin irrespective of presence or absence of glucagon. Overall, these data suggest that energy balance around parturition may regulate plasma adiponectin but do not support roles for lipid mobilization or sustained changes in the plasma concentration of leptin, insulin, growth hormone, or fatty acids.

Hepatic mRNA expression for genes related to somatotropic axis, glucose and lipid metabolisms, and inflammatory response of periparturient dairy cows treated with recombinant bovine somatotropin

Objectives of this experiment were to evaluate the effects of recombinant bovine somatotropin (rbST) treatment of periparturient dairy cows on hepatic mRNA expression for genes related to the somatotropic axis, insulin, glucose, and lipid metabolism, inflammation, and oxidative stress. Holstein cows were enrolled in the experiment at 253 ± 3 d of gestation and assigned to 1 of 3 treatments: untreated control (n = 53), 87.5 mg of rbST (n = 56; rbST87.5), and 125 mg of rbST (n = 57; rbST125). Cows in the rbST87.5 and rbST125 treatments received weekly injections of rbST from -21 to 28 d relative to calving. A subsample of cows (control = 20, rbST87.5 = 20, rbST125 = 20) was randomly selected for collection of liver samples according to expected calving date, BCS, and previous lactation 305-d mature equivalent milk yield. Only cows that had liver sampled at -21 ± 3, -7 ± 3, and 7 ± 3 d relative to calving were used in the current experiment. Blood, sampled weekly from -28 to 21 d relative to calving, was used to determine the concentrations of growth hormone, insulin-like growth factor 1, insulin, cortisol, fatty acids, β-hydroxybutyrate, glucose, haptoglobin, and tumor necrosis factor-α. Liver samples were used to determine hepatic mRNA expression of 50 genes. Treatment with rbST increased growth hormone concentrations during the postpartum period (control = 9.0 ± 0.7, rbST87.5 = 15.3 ± 1.0, rbST125 = 18.5 ± 1.3 ng/mL) and increased insulin-like growth factor 1 concentrations during the prepartum period (control = 107.4 ± 7.2, rbST87.5 = 126.9 ± 6.6, rbST125 = 139.4 ± 6.9 ng/mL). Control cows had greater postpartum concentrations of β-hydroxybutyrate (control = 776.4 ± 64.0, rbST87.5 = 628.4 ± 59.7, rbST125 = 595.4 ± 60.9 µmol/L) than rbST cows. The rbST87.5 and rbST125 treatments upregulated the hepatic mRNA expression for somatotropic axis genes (GHR, GHR1A, IGF1, IGFBP3, and SOCS2) on d -7 relative to calving and upregulated the mRNA expression for SOCS2 on d 7. On d -7, rbST87.5 and rbST125 treatments increased mRNA expression for genes involved in hepatic lipid transport (ANGPTL4, APOA5, APOB100, and SCARB1) and downregulated mRNA expression for PPARD, which is involved in lipid storage. On d 7, rbST tended to upregulate the mRNA expression for genes involved in gluconeogenesis (PCK1) and fatty acid β-oxidation (ACOX1), and downregulated the mRNA expression for genes involved in inflammation (TNFRSF1A, ICAM1, CXCL1, MYD88, HIF1A, IL1RN, NFKBIA, and SOCS3) and oxidative stress (XBP1). Administration of rbST during the periparturient period may improve liver function and health by increasing hepatic capacity for gluconeogenesis and lipid transport and by reducing inflammation and oxidative stress.

Paradoxical effects of bovine somatotropin treatment on the ovarian follicular population and in vitro embryo production of lactating buffalo donors submitted to ovum pick-up

The aim of the present study was to evaluate the effect of bovine somatotropin (bST; 500mg) administration on lactating buffalo donors submitted to two different ovum pick-up (OPU) and in vitro embryo production schemes with a 7 or 14d intersession OPU interval. A total of 16 lactating buffalo cows were randomly assigned into one of four experimental groups according to the bST treatment (bST or No-bST) and the OPU intersession interval (7 or 14d) in a 2×2 factorial design (16 weeks of OPU sessions). The females submitted to OPU every 14d had a larger (P<0.001) number of ovarian follicles suitable for puncture (15.6±0.7 vs. 12.8±0.4) and an increased (P=0.004) number of cumulus–oocyte complexes (COCs) recovered (10.0±0.5 vs. 8.5±0.3) compared to the 7d interval group. However, a 7 or 14d interval between OPU sessions had no effect (P=0.34) on the number of blastocysts produced per OPU (1.0±0.1 vs. 1.3±0.2, respectively). In addition, bST treatment increased (P<0.001) the number of ovarian follicles suitable for puncture (15.3±0.5 vs. 12.1±0.4) but reduced the percentage (18.9% vs. 10.9%; P=0.009) and the number (1.4±0.2 vs. 0.8±0.1; P=0.003) of blastocysts produced per OPU session compared with the non-bST-treated buffaloes. In conclusion, the 14d interval between OPU sessions and bST treatment efficiently increased the number of ovarian follicles suitable for puncture. However, the OPU session interval had no effect on embryo production, and bST treatment reduced the in vitro blastocyst outcomes in lactating buffalo donors.

Effect of prepartum somatotropin injection in late pregnant Holstein heifers with high body condition score on metabolic parameters, resumption of ovulation and milk production

Acosta, D. A. V., Pfeifer, L. F. M., Schmitt, E., Schneider, A., Silveira, P. A. S., Jacometo, C. B., Brauner, C. C., Rabassa, V. R., Corrêa, M. N. and Del Pino, F. A. B. 2013. Effect of prepartum somatotropin injection in late pregnant Holstein heifers with high body condition score on metabolic parameters, resumption of ovulation and milk production. Can. J. Anim. Sci. 93: 287–292. In the early post-partum period of dairy cows the duration and intensity of negative energy balance, the level of body condition score (BCS) loss and the milk yield are strongly associated with the timing of the first ovulation. The aim of this study was to determine the effect of pre-partum injections of somatotropin in dairy heifers with high BCS on the metabolism, resumption of ovarian activity and milk production. Holstein heifers (n=20) with high BCS, were divided randomly into two groups: somatotropin (n=10), which received two doses of somatotropin (500 mg) at −28 and −14 d from calving and Control (n=10), which received placebo. Blood samples were collected for evaluation of β-hydroxybutyrate (BHBA) and non-esterified fatty acids (NEFA) concentrations. Follicular development was also monitored via ultrasound. Somatotropin had no effect on plasma NEFA (P=0.35 and P=0.46) or BHBA (P=0.20 and P=0.44,) concentrations in the pre-partum and post-partum period, respectively. Milk production was not different between control (17.53±0.66 kg cow−1 d−1) and somatotropin groups (16.13±0.67 kg cow−1 d−1) (P=0.14). Pre-partum somatotropin administration did not affect (P=0.28) the time of the first post-partum ovulation. The proportion of cows ovulating the first post-partum follicular wave was not different between groups (P=0.49). In conclusion, pre-partum somatotropin treatment in dairy heifers with high body condition score seems not to have any effect on markers of energy balance, milk production or development of the first follicular wave in the early post-partum period.

Porcine somatotropin alters insulin response in growing pigs by reducing insulin sensitivity rather than changing responsiveness

Exogenous porcine somatotropin (pST) treatment consistently improves growth performance and reduces fat deposition in pigs, and it is hypothesized that one component of the mechanism is through altering the sensitivity and/or responsiveness to insulin. Therefore, a study was conducted to investigate the effect of pST treatment on whole-body glucose metabolism in response to varying doses of insulin. Eight barrows were surgically prepared with indwelling catheters and randomly assigned to one of two treatment groups (0 or 120 μg pST/kg BW · d) for 13 d. Whole-body glucose kinetics were measured during infusion of [6-3H]-glucose under basal conditions and during hyperinsulinemic-euglycemic clamps at various insulin infusion rates (7, 28, and 140, and 14, 70, and 280 ng insulin/kg BW · min) and alterations in the dose–response parameters were calculated with nonlinear regression. Treatment with pST increased basal plasma concentrations of glucose (36%; P = 0.005), insulin (276%; P = 0.001), and NEFAs (177%; P = 0.01) and decreased the rate of glucose disappearance (−59%; P = 0.001). The responsiveness (maximum response) for steady state glucose infusion rate to maintain glycemia was not altered by pST (112 vs 106 μmol/min · kg; P = 0.78), whereas the sensitivity (effective dose at 50% of maximum response) was increased almost 7-fold (1.3 vs 8.7 ng/mL; P = 0.027). Similar responses were observed for rate of glucose disappearance and insulin-dependent glucose utilization. Therefore, pST-induced insulin resistance with regard to whole-body glucose uptake is due to a reduced sensitivity to insulin, rather than a change in responsiveness.

Effect of prepartum somatotropin injection in late-pregnant Holstein heifers on metabolism, milk production and postpartum resumption of ovulation

The aim of this study was to determine the effect of prepartum somatotropin injection in late-pregnant Holstein heifers on metabolism, milk production and resumption of postpartum ovulation. For this study, 31 late-pregnant Holstein heifers were used. The heifers were assigned randomly into two treatments: (1) 500 mg sc injections of somatotropin (somatotropin treatment, n = 15) at −35 and −21 days, and, if pertinent, at −7 days from expected calving date and (2) no treatment (control group, n = 16). Blood samples were collected weekly from −5 to 7 weeks after calving. Heifers with progesterone concentrations in plasma above 1 ng/ml in two consecutive postpartum samples were considered as having resumed ovarian activity. A higher proportion (P = 0.04) of heifers treated with somatotropin resumed ovarian activity in the first 7 weeks post partum (73.3%; 11/15) compared with the control group (37.5%; 6/16). A higher number (P = 0.02) of heifers in the somatotropin treatment group also ovulated during the first postpartum follicular wave (53.3%; 8/15) compared with the control group (12.5%; 2/16), as indicated by the number of heifers ovulating in the first 3 weeks post partum. Pregnancy rate was not affected by treatments (P > 0.10) and averaged 40.0% (6/15) in somatotropin-treated and 25.0% (4/16) in control heifers when evaluated up to 150 days in milk. Somatotropin treatment increased the average daily milk production by 2.8 kg/cow per day (P < 0.0001) and reduced the somatic cell count (P = 0.009). Plasma IGF-I was higher (P < 0.05) for somatotropin-treated heifers in the prepartum period. Insulin and body condition score were higher (P < 0.05) and non-esterified fatty acids were lower (P < 0.05) for somatotropin-treated cows in the early postpartum period. In conclusion, somatotropin injection during the prepartum period in late-pregnant Holstein heifers was able to increase the proportion of heifers resuming ovarian activity early post partum, inspite of higher milk production.

Maternal low-dose porcine somatotropin treatment in late gestation increases progeny weight at birth and weaning in sows, but not in gilts1

Birth weight positively predicts postnatal growth and performance in pigs and can be increased by sustained maternal porcine ST (pST) treatment from d 25 to 100 of pregnancy (term ∼115 d). The objective of this study was to test whether a shorter period of maternal pST treatment in late pregnancy (d 75 to 100) could also increase birth and weaning weights of progeny under commercial conditions. Gilts (parity 0) and sows (parities 2 and 3) were not injected (controls) or injected daily with pST (gilts: 2.5 mg•d(-1), sows: 4.0 mg•d(-1), both ∼13 to 14 μg•kg(-1)•d(-1)) from d 75 to 100 of pregnancy. Litter size and BW were recorded at birth and weaning, and dams were followed through the subsequent mating and pregnancy. Maternal pST injections from d 75 to 100 increased litter average progeny weight at birth (+96 g, P = 0.034) and weaning (+430 g, P = 0.038) in sows, but had no effect on progeny weight in gilts (each P > 0.5). Maternal pST treatment did not affect numbers of live-born piglets and increased numbers of stillborn piglets in sows only (+0.4 pigs/litter, P = 0.034). Maternal pST treatment did not affect subsequent reproduction of dams. Together with our previous data, these results suggest that sustained increases in maternal pST are required to increase fetal and postnatal growth in gilt progeny, but that increasing maternal pST in late pregnancy may only be an effective strategy to increase fetal and possibly postnatal growth in sow progeny.

Somatotropic gene response to recombinant somatotropin treatment in buffalo leukocytes

The septins are a conserved family of guanine nucleotide binding proteins, often named the fourth component of the cytoskeleton. They self-assemble into non-polar filaments and further into higher ordered structures. Properly assembled septin structures are required for a wide range of indispensable intracellular processes such as cytokinesis, vesicular transport, polarity establishment and cellular adhesion. Septins belong structurally to the P-Loop NTPases. However, unlike the small GTPases like Ras, septins do not mediate signals to effectors through GTP binding and hydrolysis. The role of nucleotide binding and subsequent GTP hydrolysis by the septins is rather controversially debated. We compile here the structural features from the existing septin crystal- and cryo-EM structures regarding protofilament formation, inter-subunit interface architecture and nucleotide binding and hydrolysis. These findings are supplemented with a summary of available biochemical studies providing information regarding nucleotide binding and hydrolysis of fungal and mammalian septins.

Effect of exogenous somatotropin in Holstein calves on mammary gland composition and proliferation

Pubertal mammary gland growth and development are hormonally regulated, but the details are poorly understood in calves. Our purpose was to evaluate the effects of exogenous growth hormone (GH) on the biochemical composition of the prepubertal mammary gland, mRNA expression of selected genes, and histological characteristics of the developing parenchyma (PAR). In this experiment, 19 calves (7±4 d of age) were randomly assigned to 1 of 2 treatments: bovine somatotropin (bST, 500mg; n=10) or placebo (Sal; 0.9% saline; n=9). Animals were treated every 3 wk beginning on d 23. Calves were assigned to an early (65 d; tissue harvested after 2 treatment injections) or late collection time (107 d; tissue harvested after 4 treatment injections). Calves were fed milk replacer and calf starter for 8 wk and starter and hay thereafter. Parenchyma and mammary fat pad (MFP) from one udder half were harvested for analysis of protein, lipid, and DNA. Additional tissues were preserved for histological analysis or snap-frozen for quantitative real-time PCR. Somatotropin treatment did not significantly alter the mass of PAR or MFP or the general pattern of development of epithelial structures. Significant increases were observed in protein/100kg of body weight (BW), total protein, DNA concentration, DNA/100kg of BW, and total DNA in 107-d calves, and a significant treatment by day interaction was observed for DNA and lipid concentrations in PAR. In MFP, a significant decrease was observed in protein/100kg of BW in bST-treated calves and in total MFP protein in 65-d calves. A treatment by day interaction was found for total protein, DNA, and protein/100kg of BW. In PAR, relative expression of ATPase-binding cassette 3 and growth hormone receptor were reduced by bST and both were lower in 107-d-harvest calves. Epithelial cell retention of bromodeoxyuridine (BrdU; possible indicator of stem-like cells) was greatest in 65-d bST-treated calves, and a significant time of sampling response and treatment × time interaction were observed. Expression of the proliferation marker protein Ki67 was numerically higher in bST-treated calves but the difference was nonsignificant. Retention of the BrdU label was reduced in 107-d calves. Exogenous growth hormone given to calves may affect mammary tissue composition and epithelial cell gene expression in subtle ways but exogenous supplementation with bST alone is not likely to alter overall development patterns or affect the mass of mammary parenchymal tissue. Whether such subtle changes have an effect on subsequent development or function is unknown.

Somatotropin-mediated gene expression profiling of differentially displayed ESTs during lactation in Indian buffalo (Bubalus bubalis)

The study of bovine mammary gland functional genomics requires appropriate cDNA library collections to access gene expression patterns from different developmental and physiological stages. The present study was undertaken with the objective to identify candidate genes involved in the process of increased milk synthesis following 0, 48 and 96 h of recombinant bovine somatotropin (rbST) treatment to Surti buffalo (Bubalus bubalis) through differential display reverse transcriptase PCR (DDRT-PCR). Of a total 50 sequenced DD bands, 64% of ESTs were differentially expressed (appeared only in post-treatment samples, i.e. 48 h and 96 h) and 36% were up-regulated after rbST treatment. Of the ESTs 32%were found to be located on Bos taurus chromosome 24 (equivalent to buffalo chromosome 22), whereas 16% of ESTs could not be mapped, indicating that they are specific to buffalo. Quantitative real time PCR assay of 15 ESTs revealed transcript level surge in 13 ESTs, and decline in one EST, while one showed up-regulation in expression level at 48 h while down-regulation at 96 h. This study indicates more than 30 novel transcripts, with unknown function, involved in increased milk synthesis and also the involvement of many more genes in the physiology of milk production than once thought.