Plasma IGF-I Concentrations Research Articles

Effects of age on thermoregulatory responses during cold exposure in a nonhuman primate, Microcebus murinus

Cold resistance appears altered with aging. Among existing hypotheses, the impaired capacity in response to cold could be related to an altered regulation of plasma IGF-1 concentration. The combined effects of age and cold exposure were studied in a short-living primate, the gray mouse lemur (Microcebus murinus), which adjusts its energy balance using a daily torpor phase, to avoid high energy cost of normothermia maintenance. Changes in body mass, core temperature, locomotor activity, and caloric intake were monitored under 9-day exposures to 25 degrees C and 12 degrees C in captive animals in winter conditions. Short-term (after 2 days) and long-term (after 9 days) cold-induced changes in IGF-1 levels were also evaluated. In thermoneutral conditions (25 degrees C), general characteristics of the daily rhythm of core temperature were preserved with age. At 12 degrees C, age-related changes were mainly characterized by a deeper hypothermia and an increased frequency of torpor phases, associated with a loss of body mass. A short-term cold-induced decrease in plasma IGF-1 levels was observed. IGF-1 levels returned to basal values after 9 days of cold exposure. No significant effect of age could be evidenced on IGF-1 response. However, IGF-1 levels of cold-exposed aged animals were negatively correlated with the frequency of daily torpor. Responses exhibited by aged mouse lemurs exposed to cold revealed difficulties in the maintenance of normothermia and energy balance and might involve modulations of IGF-1 levels.

Sex-related variation in compact bone microstructure of the femoral diaphysis in juvenile rabbits

BackgroundWhile gross morphological changes in the skeleton between males and females are well know, differences between sexes in the histomorphology are less known. It is important to have knowledge on the bone structure of rabbits, as this is a widely used species in biomedical research. A study was performed to evaluate the association between sex and the compact bone morphology of the femoral diaphysis in juvenile rabbits.MethodsSeventeen clinically healthy 2–3 month-old rabbits (9 females, 8 males) were included in the study. The rabbits were euthanized and the right femur was sampled for analysis. 70–80 microns thick bone sections of the femoral diaphysis were prepared using standard histological equipment. The qualitative histological characteristics were determined according to internationally accepted classification systems while the quantitative parameters were assessed using the software Scion Image. Areas, perimeters, minimum and maximum diameters of primary osteons' vascular canals, Haversian canals and secondary osteons were measured. Additionally, blood plasma concentrations of progesterone, corticosterone, IGF-I, testosterone and estradiol were analyzed.ResultsQualitative histological characteristics were similar for both sexes. However, variations of certain quantitative histological characteristics were identified. Measured parameters of the primary osteons' vascular canals were higher in males than for females. On the other hand, females had significant higher values of secondary osteons parameters. Differences in Haversian canals parameters were only significant for minimum diameter.ConclusionThe study demonstrated that quantitative histological characteristics of compact bone tissue of the femoral diaphysis in juvenile rabbits were sex dependent. The variations may be associated with different growth and modeling of the femur through influence by sex-specific steroids, mechanical loads, genetic factors and a multitude of other sources. The results can be applied in experimental studies focusing on comparison of the skeletal biology of the sexes.

Effects of body condition score at parturition and postpartum protein supplementation on estrous behavior and size of the dominant follicle in beef cows1,2

The objective of this study was to determine the effects of BCS at calving and the amount of postpartum protein supplementation on the dominant follicle (DF) and behavioral characteristics at the first postpartum estrus of mature beef cows. Multiparous Angus x Hereford cows (n = 45) were fed to calve in thin (T; < 5) or moderate (M; >or=5) BCS. Cows were stratified by BCS and calving date, and randomly assigned to receive lesser (L; 1.2 kg/d) or greater (G; 2.5 kg/d) amounts of a 42% CP supplement. All cows grazed the same native grass pasture and were fed in individual stalls for 49 +/- 2 d. Beginning 20 d after calving, blood samples were collected from each cow thrice weekly, and estrous behavior was monitored continuously with a radiotelemetry system. At 4 to 16 h after the onset of estrus, size of the DF was determined by ultrasonography. Body condition score of T cows was less (P < 0.01) at calving than M cows; L and G cows had similar BCS at calving and at the end of the feeding period. Body weight gains during treatment did not differ for L or G cows. Duration from calving to first estrus was greater (P < 0.01) for T than M cows. The incidence of a short luteal phase before first estrus was not influenced by BCS or protein supplement. Concentrations of IGF-I in plasma tended (P < 0.07) to be greater and size of the DF was greater (P < 0.01) for M than T cows. Size of the DF tended (P < 0.06) to be greater for G than L cows. Duration and number of mounts received at the first estrus were not influenced by BCS or supplement. Pregnancy rate of M cows during the breeding season was greater (P < 0.05) than T cows. Postpartum protein intake and BCS at calving influenced the size of the DF at the first postpartum estrus in mature suckled beef cows. Cows should be managed to calve in moderate BCS and maintain BW after parturition to decrease the interval to first estrus, increase follicular development, and maximize pregnancy rate.

Whole sunflower seeds as a source of polyunsaturated fatty acids for grazing dairy cows: Effects on metabolic profiles and resumption of postpartum ovarian cyclicity

Intake of polyunsaturated fatty acids (PUFA) could modify follicular dynamics and reduce the length of the interval from calving to first ovulation (ICOV) in dairy cows, associated with changes in metabolites (i.e. cholesterol) or hormones (i.e. IGF-I). To test this hypothesis, 48 cows were stratified in two groups (primiparous or multiparous) and within each group were randomly assigned to three treatments to begin at calving: 0 kg (SS0), 0.7 kg (SS0.7) and 1.4 kg (SS1.4) of whole sunflower seeds (WSS) per cow per day. The experimental period lasted for 60 days after calving and the diets, which consisted of direct grazing of improved pastures, whole-plant wheat silage and concentrates, were designed to be isocaloric and isoproteic (1.6 Mcal NEL/kg DM, 16.7% CP). Ovaries were examined by ultrasound three times per week from day 8 postpartum (PP) until first PP ovulation. Body condition score (BCS) was determined and blood samples were collected weekly from calving to characterize the metabolic profiles. In treatments SS0.7 and SS1.4, 7/8 and 6/8 primiparous cows ovulated the first follicular wave PP, compared with only 1/8 primiparous cow in treatment SS0, while there were no treatment differences in multiparous cows. The ICOV was 44, 21 and 19 days for the primiparous, and 22, 21 and 25 days for the multiparous cows, in treatments SS0, SS0.7 and SS1.4, respectively. Treatments had no effect on BCS, plasma IGF-I and metabolic profiles except that NEFA and urea were increased by WSS supplementation. Intake of PUFA (WSS up to 1.4 kg/day or 6.7% of the diet) during early lactation reduced the ICOV in primiparous grazing dairy cows in early lactation but not in multiparous cows, and while the precise mechanism for these results is unclear, it was not related to changes in the plasma concentrations of IGF-I or cholesterol.

Treatment of Pituitary Gigantism with the Growth Hormone Receptor Antagonist Pegvisomant

Treatment of pituitary gigantism is complex and the results are usually unsatisfactory. The objective of the study was to describe the results of therapy of three children with pituitary gigantism by a GH receptor antagonist, pegvisomant. This was a descriptive case series of up to 3.5 yr duration. The study was conducted at a university hospital. Patients included three children (one female, two males) with pituitary gigantism whose GH hypersecretion was incompletely controlled by surgery, somatostatin analog, and dopamine agonist. The intervention was administration of pegvisomant. Plasma IGF-I and growth velocity were measured. In all three children, pegvisomant rapidly decreased plasma IGF-I concentrations. Growth velocity declined to subnormal or normal values. Statural growth fell into lower growth percentiles and acromegalic features resolved. Pituitary tumor size did not change in two children but increased in one boy despite concomitant therapy with a somatostatin analog. Pegvisomant may be an effective modality for the therapy of pituitary gigantism in children. Titration of the dose is necessary for optimal efficacy, and regular surveillance of tumor size is mandatory.

Effect of Variable Long-Term Maternal Feed Allowance on the Development of the Ovine Placenta and Fetus

Maternal feed allowance during pregnancy can affect the development of the ovine placenta and fetus. The impact of variations in feed allowance prior to as well as throughout pregnancy has received less attention. Ewes were offered 0.6 (R), 1.2 (C) or 1.8 (AL) maintenance requirements from 89 days before conception until day 133 of pregnancy. Ewes were euthanased on days 50, 92 and 133 of pregnancy. Ewe live weight and body condition score, maternal and fetal metabolic and hormonal profiles, fetal body dimensions and organ weights, and the number, weight and morphology of placentomes were measured. Maternal live weight and condition score were lower in R compared to AL ewes at all stages of pregnancy ( P < 0.05). Plasma glucose and albumin concentrations of R ewes were significantly reduced ( P < 0.05) at mid and late gestation, respectively. Placental components were generally unresponsive to long term variations in maternal feed allowance. However, placental weight was significantly ( P < 0.05) correlated with fetal weight at days 50 ( r = 0.59) and 133 ( r = 0.69) of gestation. By late gestation growth-retarded singleton fetuses from R ewes were 19% lighter ( P < 0.05), with reduced abdominal (9%) and thoracic (10%) girths ( P<0.05) but of similar crown-rump length compared with fetuses from AL ewes. These differences were associated with significantly reduced IGF-I concentrations in fetal plasma ( P < 0.05). In conclusion, maternal, placental and fetal adaptations to long established planes of variable maternal feed allowance were able to maintain fetal growth during early and mid-pregnancy while fetal growth restriction, associated with reduced fetal IGF-I levels, became apparent in late pregnancy.

Effect of dried corn distillers grains plus solubles compared with soybean hulls, in late gestation heifer diets, on animal and reproductive performance1

Dried distillers grains plus solubles (DDGS) contain fat and rumen undegradable intake protein, both of which have been shown to increase reproductive performance in heifers. The mechanisms leading to enhanced reproduction have not been fully defined. The objectives of this research were to evaluate effects of DDGS in late gestation heifer diets on animal and reproductive performance and on blood plasma concentrations of GH, IGF-I, and NEFA. Over 2 yr, 201 heifers were randomly allotted to 1 of 2 diets, which were similar in energy and adequate in rumen degradable intake protein and were fed from d 190 of gestation through calving. Diets were grass hay with DDGS or soybean hulls (SBH) and a supplement. Cow BW and BCS were measured from the beginning of treatment through weaning. Blood samples were collected prepartum on d 71 and 69 of the feeding period and weekly after calving for 4 and 6 wk (d 84 to 105 and d 76 to 111 relative to the feeding period) during yr 1 and 2, respectively. No treatment x year interactions were detected for any of the performance, hormonal, or reproductive dependent variables. Both treatments caused positive BW changes over the feeding period, but DDGS heifers had a greater (P < 0.01) positive BW change compared with SBH heifers. Initial and final BCS and BCS change were similar (P >/= 0.26) between DDGS and SBH treatments. Treatment did not influence (P >/= 0.12) BW or BCS change during the postpartum period. Calving ease, calf vigor, and calf birth weight, weaning weight, and ADG (birth to weaning) were similar (P >/= 0.41) between treatments. The proportion of cows that had initiated estrous cycles (P = 0.46) and the pregnancy distribution (P >/= 0.21) were similar between treatments. However, a greater (P = 0.058) percentage of DDGS cows became pregnant compared with SBH cows (94 and 84%). In both years, there were no effects of treatment (P >/= 0.17) or treatment x time (P >/= 0.52), but time influenced (P </= 0.05) the concentrations of GH, IGF-I, and NEFA. Concentrations of GH were greater (P </= 0.05) at calving and decreased through d 4 after calving. The IGF-I concentrations were greater (P < 0.01) around calving and decreased (P < 0.05) through d 8 or 6 (yr 1 or 2) and remained similar (P > 0.10) for the duration of the sampling period. Concentrations of NEFA increased from calving through d 8 and gradually declined through d 20. Prepartum diets containing DDGS, a source of fat and UIP, benefited pregnancy rates in well-maintained, primiparous beef heifers.

Changes of activity and mRNA expression of urea cycle enzymes in the liver of developing Holstein calves1

Urea is an important reutilizable nitrogen source for the ruminant and is mainly synthesized through the urea cycle in the liver. The cycle is undertaken by 5 enzymes: carbamoyl phosphate synthetase (CPS), ornithine transcarbamoylase (OTC), arginino-succinate synthetase (AS), argininosuccinate lyase (AL), and arginase. The purpose of this study was to investigate changes in the activity of the enzymes and mRNA expression, given that previous observations have indicated an increase in plasma urea concentrations with age in Holstein calves. First, plasma concentrations of metabolites and hormones were determined in calves at 1, 3, 8, 13, and 19 wk of age (n = 4, weaned at 6 wk of age). The plasma concentration of urea drastically increased after weaning (P < 0.001). The plasma concentration of glucose was lowest at 8 wk. The plasma concentration of IGF-I gradually increased with age, although those of NEFA, glucagon, and cortisol decreased (P < 0.001). Concentrations of triglyceride, alpha-amino nitrogen, growth hormone, and insulin did not change significantly with age of the calf. Next, using the liver tissues taken from calves at 2, 13, and 19 wk of age (n = 4 to 6 at each time point, weaned at 6 wk of age), we measured the activity and mRNA expression of the enzymes by biochemical methods and quantitative reverse transcription-PCR, respectively. The activities of CPS (P < 0.001), OTC (P = 0.001), and AS (P = 0.015) increased with age, whereas AL (P = 0.003) decreased. Although mRNA expression was decreased with age for AL (P = 0.002) and arginase (P = 0.007), no significant change was observed for CPS, OTC, or AS mRNA expression. We conclude that the increased urea production in the liver may be explained not only by an increase in the activities of the urea cycle enzymes, but also by increased ammonia production by rumen fermentation and gluconeogenesis from amino acids around weaning time.

Supplementation of Holstein Cows with Low Doses of Bovine Somatotropin (bST) Prepartum and Postpartum Affects Physiological Adaptations and Milk Production

Major objectives were to evaluate effects of three schemes of bST-supplementation of Holstein cows (142.8 mg/14 d, POSILAC) during the prepartum and/or postpartum periods through 63 d (±3 d) of lactation. Measures evaluated the potential of treatments to improve body weight (BW) and body condition score (BCS), provoke changes in plasma concentrations of somatotropin (ST) and IGF-I, and improve milk yield, milk composition (percentages of protein and fat, and somatic cell counts), and several calving variables. Multiparous Holstein cows were randomly assigned to a 2x2 factorial arrangement of treatments (TRT) to give four groups (I = no bST, n = 26; II = bST postpartum, n = 25; III = bST prepartum, n = 27; IV = bST prepartum and postpartum, n = 25). During the prepartum period, cows in groups I and II were not supplemented but those in groups III and IV were supplemented every 2-wk beginning 21 d before expected calving date through calving. During the first 63 DIM only cows in groups II and IV were supplemented with bST. From 64 DIM through the end of lactation cows in all groups were supplemented with the full lactation dose of bST (500 mg/14 d). The BW and BCS were recorded weekly throughout the prepartum and postpartum periods and every 2-wk beyond 70 DIM. Blood samples were collected 3-times a week for analyses of ST and IGF-I. Milk yields were recorded daily though 150 DIM. Prepartum supplementation of bST did not affect BW or BCS, but mean concentrations of ST were increased 12.2% and were 15.5% greater at calving. Overall, mean concentration of IGF-I was not affected by treatment but concentrations were greater at 1 and 2 wk before calving in bST-supplemented cows. During the first 63 DIM the BW and BCS were not affected by treatment. Significant effects of bST-supplementation were detected on concentrations of ST, IGF-I and on milk yield compared to non-supplemented cows in group I. Postpartum concentrations of ST were greater in bST-supplemented cows (TRT II and IV; +41.9 and 54.6%). However, concentrations of IGF-I were greater only in cows in group IV (+25.9%) during the postpartum period. Overall, the three bST-supplemented groups had greater actual milk yield than the control group (I) during the first 63 and 150 DIM. The actual milk yields during 63 and 150 DIM were 6.5 and 4.6 kg/d greater for cows in group IV than cows in group I and the 305-d ME milk yield also was 15.6% greater. No adverse effects of TRT were observed on calf birth weight, colostrum immunoglobulins, ease of calving or other measures evaluated.

Effect of prolonged intravenous glucose and essential amino acid infusion on nitrogen balance, muscle protein degradation and ubiquitin-conjugating enzyme gene expression in calves

BackgroundIntravenous infusions of glucose and amino acids increase both nitrogen balance and muscle accretion. We hypothesised that co-infusion of glucose (to stimulate insulin) and essential amino acids (EAA) would act additively to improve nitrogen balance by decreasing muscle protein degradation in association with alterations in muscle expression of components of the ubiquitin-proteasome proteolytic pathway.MethodsWe examined the effect of a 5 day intravenous infusions of saline, glucose, EAA and glucose + EAA, on urinary nitrogen excretion and muscle protein degradation. We carried out the study in 6 restrained calves since ruminants offer the advantage that muscle protein degradation can be assessed by excretion of 3 methyl-histidine and multiple muscle biopsies can be taken from the same animal. On the final day of infusion blood samples were taken for hormone and metabolite measurement and muscle biopsies for expression of ubiquitin, the 14-kDa E2 ubiquitin conjugating enzyme, and proteasome sub-units C2 and C8.ResultsOn day 5 of glucose infusion, plasma glucose, insulin and IGF-1 concentrations were increased while urea nitrogen excretion and myofibrillar protein degradation was decreased. Co-infusion of glucose + EAA prevented the loss of urinary nitrogen observed with EAA infusions alone and enhanced the increase in plasma IGF-1 concentration but there was no synergistic effect of glucose + EAA on the decrease in myofibrillar protein degradation. Muscle mRNA expression of the ubiquitin conjugating enzyme, 14-kDa E2 and proteasome sub-unit C2 were significantly decreased, after glucose but not amino acid infusions, and there was no further response to the combined infusions of glucose + EAA.ConclusionProlonged glucose infusion decreases myofibrillar protein degradation, prevents the excretion of infused EAA, and acts additively with EAA to increase plasma IGF-1 and improve net nitrogen balance. There was no evidence of synergistic effects between glucose + EAA infusion on muscle protein degradation or expression of components of the ubiquitin-proteasome proteolytic pathway.

Energy balance, leptin, NEFA and IGF-I plasma concentrations and resumption of post partum ovarian activity in swedish red and white breed cows

In the purpose to provide further information in respect of the relationship between metabolism and post partum (PP) ovarian activity resumption in dairy cows, the aim of the present study was to characterize the energy balance (EB) and leptin, NEFA and IGF-I plasma levels in Swedish Red and White (SRW) cows with and without ovarian activity re-initiation within 7 weeks PP. The study was conducted on 12 primiparous SRW cows fed the same diet as total mixed ration for ad libitum intake. The EB was calculated weekly from parturition until seven weeks PP. Blood samples were collected weekly from one week before until 7 weeks after calving for leptin, NEFA and IGF-I analysis. For progesterone (P4) analysis, blood samples were collected two times per week from parturition until the end of the study. P4 profile was used in addition to the clinical examination to detect cows with and without ovarian activity resumption. The clinical and ultrasonographic examination, coupled with P4 profile analysis showed the resumption of ovarian activity within 7 weeks after calving in 8 (group A) and no ovarian resumption in 4 cows (group B). No significant differences were detected in the whole period of observation in the amount of milk production between the two groups, while the mean milk protein content was significantly lower in group B at the third week PP. The calculated EB was negative in both groups in the first three weeks after calving, but more marked in group B. NEFA and Leptin plasma levels did not show significant differences between the two groups. In conclusion, the results of the present study showed that, when low milk producing primiparous cows are concerned, no significant differences in BW loss, milk yield, EB and leptin and NEFA plasma levels between the cows with and without resumption of ovarian activity within 7 weeks post partum were seen. However, significantly higher IGF-I levels in the first two weeks after calving were found in cows with post partum ovarian activity resumption, highlighting the important role of IGF-I as sensitive signal between metabolism and reproduction.

Growth Hormone Exerts Acute Vascular Effects Independent of Systemic or Muscle Insulin-like Growth Factor I

Endothelial dysfunction is common in patients with GH deficiency who are at increased risk for premature cardiovascular death. GH regulates vascular tone and reactivity in humans. Our objective was to explore the mechanisms underlying the GH's acute vascular effects. DESIGN AND STUDY SETTING: There were 10 healthy, lean and young, volunteers studied after an overnight fast. GH was infused systemically for 6 h at 0.06 microg/kg.min. Biopsy of the vastus lateralis muscle was done in seven subjects before and after GH infusion. Human aortic endothelial cells (HAECs) were incubated with GH in vitro. GH infusion increased plasma GH to 32.9 +/- 1.5 ng/ml and forearm blood flow by 66% (P < 0.001). GH infusion did not significantly change plasma IGF-I concentrations, muscle IGF-I mRNA expression, and muscle Akt phosphorylation, suggesting a lack of IGF-I action in muscle. Because it was reported that GH exerts an acute vascular effect via a nitric oxide (NO)-dependent mechanism, we performed additional in vitro experiments using HAECs. HAECs express abundant GH receptors. Incubating HAECs with GH at 30 ng/ml for 3 or 6 h did not alter endothelial NO synthase (eNOS) protein content but time dependently increased the phosphorylation and activity of eNOS, thus demonstrating a direct effect of GH on endothelial cells. GH exerts an acute vascular effect independent of both systemic and local IGF-I production, and this effect is likely via direct action on GH receptors and eNOS in the vascular endothelium.

Uterine and Hepatic Gene Expression in Relation to Days Postpartum, Estrus, and Pregnancy in Postpartum Dairy Cows

The somatotropic axis consisting of growth hormone, the growth hormone receptor (GHR) insulin-like growth factor (IGF)-I, and IGF binding proteins changes with the stage of lactation and nutrition of the cow and may be 1 mechanism through which lactation and nutrition affect the establishment of pregnancy. The objective of this study was to quantify GHR, IGF-I, and IGF binding protein-2 (IGFBP-2) mRNA in liver and uterine endometrial tissue at 4 stages of lactation (40, 80, 120, and 160 days in milk) and around the time of artificial insemination. Estrus was synchronized with GnRH and PGF2α, and cows were inseminated 12h after estrus. Uterine biopsies were collected immediately before the second injection of PGF2α (before estrus), at the initiation of standing estrus, and 4 d after estrus. Liver biopsies were collected once on 4 d after estrus. The abundance of GHR, IGF-I, and IGFBP-2 mRNA in liver and uterus was determined by real-time quantitative PCR. The amount of liver IGF-I mRNA was positively correlated with plasma IGF-I concentrations. Cows that became pregnant after AI had more GHR and IGFBP-2 mRNA in their liver than cows that did not become pregnant. There was no effect of DIM or pregnancy status on abundance of uterine mRNA; however, uterine GHR and IGF-I mRNA was most abundant at estrus. In summary, cows at different stages of lactation or with different pregnancy statuses had similar quantities of uterine mRNA. In contrast, liver quantities of mRNA differed relative to pregnancy status. These data provide evidence that liver indices of metabolic state may be indicative of pregnancy success.

A comparison of energy balance and metabolic profiles of the New Zealand and North American strains of Holstein Friesian dairy cow

The milk production, energy balance (EB), endocrine and metabolite profiles of 10 New Zealand Holstein Friesian (NZ) cows and 10 North American Holstein Friesian (NA) cows were compared. The NA cows had greater peak milk yields and total lactation milk yields (7387 v. 6208 kg; s.e.d. = 359), lower milk fat and similar protein concentrations compared with the NZ cows. Body weight (BW) was greater for NA cows compared with NZ cows throughout lactation (596 v. 544 kg; s.e.d. = 15.5), while body condition score (BCS) tended to be lower. The NA strain tended to have greater dry matter intake (DMI) (17.2 v. 15.7 kg/day; s.e.d. = 0.78) for week 1 to 20 of lactation, though DMI as a proportion of metabolic BW was similar for both strains. No differences were observed between the strains in the timing and magnitude of the EB nadir, interval to neutral EB, or mean daily EB for week 1 to 20 of lactation. Plasma concentrations of glucose and insulin were greater for NA cows during the transition period (day 14 prepartum to day 28 postpartum). Plasma IGF-I concentrations were similar for the strains at this time, but NZ cows had greater plasma IGF-I concentration from day 29 to day 100 of lactation, despite similar calculated EB. In conclusion, the results of this study do not support the premise that the NZ strain has a more favourable metabolic status during the transition period. The results, however, indicate that NZ cows begin to partition nutrients towards body reserves during mid-lactation, whereas NA cows continue to partition nutrients to milk production.

Late gestational nutrient restriction: Effects on ewes' metabolic and homeorhetic adaptation, consequences for lamb birth weight and lactation performance

We investigated the effect of 50% nutrient restriction during the last 6 weeks ofgestation on twin-pregnant ewes' plasma glucose, non-esterified fatty acid, β-hydroxybutyrate, insulin, IGF-1 and leptin concentrations and the effects on lamb birth weight and ewes' lactation performance. Plasma metabolite and hormone concentrations in restricted ewes suggest that maternal tissues were being mobilised. Despite the ewes' adaptations their lambs weighed significantly less at birth. Furthermore, colostrum and milk yields were markedly reduced up until the latest measurement at 3 weeks post partum despite ad libitum access to feed. Reduced milk yields coincided with reduced plasma IGF-1 concentration pre partum in nutrient restricted ewes indicating, that mammary gland development may have been compromised. The present data suggest that leptin is not involved in the regulation of early lactation changes in feed intake and energy balance. It is concluded that severely reduced nutrient availability in late gestation affects fetal growth in utero and has a prolonged negative effect on lactation performance.

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 8 g/day phloridizin (PHZ) and seven control animals (CTRL, 0 g/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.

Metabolic Effects of Oral Versus Transdermal Estrogen in Growth Hormone-Treated Girls with Turner Syndrome

Transdermal (TD) estrogen is often preferred over the oral route in postmenopausal and GH-deficient women taking estrogen, but this has not been studied in detail in girls. Our objective was to study the metabolic effects of oral vs. TD estrogen in GH-treated girls with Turner syndrome. Eleven girls with Turner syndrome, mean age 13.4 +/- 0.5 (se) yr, on GH for at least 6 months were recruited. Studies included [(13)C]leucine and d5-glycerol infusions, indirect calorimetry, dual-emission x-ray absorptiometry, and hormone and substrate measurements. They received, in random order, 17beta-estradiol orally (0.5, 1, and 2 mg for 2 wk each) and TD (0.025, 0.0375, and 0.05 mg for 2 wk each), and studies were repeated after each 6-wk course with 4 wk washout in between. Rates of whole-body protein turnover, oxidation and synthesis, lipolysis, lipid and carbohydrate oxidation, and resting energy expenditure were unaffected by either form of estrogen; nor were lipids, insulin, and fibrinogen concentrations affected. Plasma IGF-I concentrations did not change clinically significantly with either form of estrogen, despite higher estrogen concentrations after oral estrogen. Estradiol concentrations did not correlate with any variables measured. In GH-treated girls with Turner syndrome, neither oral nor TD estrogen adversely affected rates of protein turnover, lipolysis, and lipid oxidation rates or plasma lipids, fibrinogen, or fasting insulin concentrations. There was no clinically significant change in IGF-I concentrations after either form of estrogen. In aggregate, these data suggest that the route of delivery of estrogen does not adversely affect these metabolic effects of GH in young girls with Turner syndrome.

Insulin-like Growth Factors and Ovarian Cancer Risk: A Nested Case-Control Study in Three Cohorts

Insulin-like growth factor (IGF)-related hormones and binding proteins (IGFBP) have been implicated in cancer risk. Specifically, two recent, small prospective studies reported a significant positive association between IGF-I and ovarian cancer risk among women diagnosed before age 55 years. Therefore, we examined whether plasma concentrations of IGF-I, IGFBP-3, and IGFBP-2 were associated with risk of epithelial ovarian cancer in a nested case-control study using data from three prospective cohorts: the Nurses' Health Study (NHS), NHSII, and the Women's Health Study (WHS). The present study had 222 cases (159 from NHS/NHSII and 63 from WHS) and 599 controls (matching ratio, 1:3 for NHS/NHSII and 1:2 for WHS). Women ranged in age from 34 to 73 years (mean, 56 years). The relative risk (RR) comparing the top versus bottom quartile of IGF-I was 0.56 (95% confidence interval, 0.32-0.97; P(trend) = 0.14). The risk did not differ by age at diagnosis (comparable RR for age <55 years at diagnosis, 0.70; RR for age >/=55 years at diagnosis, 0.52). We did not observe any association between IGFBP-3, IGFBP-2, and the ratio of IGF-I to either binding protein and ovarian cancer risk. Overall, our results do not support a positive association between IGF-related proteins and ovarian cancer risk. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1691-5).

Effects of L-carnitine in the Gestating Sow Diet on Fetal Muscle Development and Carcass Characteristics of the Offspring

Musser, R.E., Dritz, S.S., Davis, D.L., Tokach, M.D., Nelssen, J.L., Goodband, R.D. and Owen, K.Q. 2007. Effects of L-carnitine in the gestating sow diet on fetal muscle development and carcass characteristics of the offspring. J. Appl. Anim. Res., 31: 105–111. A total of 232 sows were used to determine the effects none or an additional 50 ppm of L-carnitine in the gestation diet on sow and offspring performance. Sows were fed dietary treatments from breeding until d 110 of gestation. Offspring from sows were ear-notched according to maternal treatment at birth and carcass data were obtained at slaughter. Sow plasma IGF-I concentration was similar (P>0.10) between control and L-carnitine supplemented sows on d 30 and 60 of gestation at 2 h after feeding. No differences were observed in either the immediate or subsequent number of pigs born per litter. No differences were observed in a sub-sample (n = 181) of pig weight at birth, weaning or d 59 of age between control and treatment offspring. Analysis of newborn pigs revealed no differences in semitendinosus cross-sectional area or primary (slow-twitch, red) fibers. Offspring of sows fed L-carnitine had a numerical tendency (P = 0.11) for a lower ratio of secondary:primary fibers compared with offspring of control sows. No differences were observed in hot carcass weight (87.6 kg); however, loin depth (57.0 < vs 59.4 mm; P < 0.01) and percentage lean (54.45 vs 55.10; P < 0.01) were increased, and backfat decreased (18.4 vs 17.8 mm: P < 0.01) in offspring of sows fed L-carnitine during gestation. Therefore, while feeding L-carnitine during gestation had no effect on the number of pigs born, it improved carcass leanness of the offspring at market weight and tended to lower ratio of secondary.—primary fibers at birth.

Effects of supplement type on performance, reproductive, and physiological responses of Brahman-crossbred females1

Two experiments were conducted to compare the performance and physiological responses of forage-fed beef females supplemented with either a molasses-based (ML) or a citrus pulp-based (CT) supplement. In Exp. 1, BW gain, reproductive performance, and concentrations of blood urea N (BUN), plasma glucose, insulin, IGF-I, and progesterone (P4) were assessed in 60 Brahman x Angus heifers supplemented 3 times weekly with either ML or CT. Supplement intakes were formulated to be isocaloric and isonitrogenous. Reproductive performance was not affected by treatments, but mean BW gain was greater (P < 0.01) for heifers fed CT than for those fed ML (0.40 vs. 0.30 kg/d). Mean plasma concentrations of glucose, insulin, and IGF-I were greater (P < 0.05) for heifers fed CT, whereas BUN was greater (P < 0.05) for heifers fed ML. Mean plasma P4 concentration did not differ between treatments, but both groups had lower plasma P4 concentrations during days that supplements were offered (P < 0.01). In Exp. 2, forage DMI and concentrations of BUN, plasma glucose, insulin, IGF-I, and P4 were assessed in 24 Brahman x British mature cows supplemented with the same treatments described in Exp. 1. Overall forage DMI did not differ between treatments, but a day effect and a treatment x day interaction were detected (P < 0.05). Both groups consumed less forage during the days on which the supplements were offered (P < 0.01), and forage DMI for cows fed CT was less (P < 0.05) than for cows fed ML during those days. No differences were detected in any blood or plasma measurement. In addition, no differences in concentrations of P4 were detected between CT- and ML-fed cows. We concluded that CT-supplemented heifers had greater BW gain compared with ML-supplemented heifers, but no differences in reproductive performance were observed. We also observed that CT-supplemented cows had a greater variability in forage DMI compared with ML-supplemented cows.