Search

Feedback on chest compressions and ventilations during cardiopulmonary resuscitation (CPR) is important to improve survival from out-of-hospital cardiac arrest (OHCA). The thoracic impedance signal acquired by monitor-defibrillators during treatment can be used to provide feedback on ventilations, but chest compression components prevent accurate detection of ventilations. This study introduces the first method for accurate ventilation detection using the impedance while chest compressions are concurrently delivered by a mechanical CPR device. A total of 423 OHCA patients treated with mechanical CPR were included, 761 analysis intervals were selected which in total comprised 5 884 minutes and contained 34 864 ventilations. Ground truth ventilations were determined using the expired CO 2 channel. The method uses adaptive signal processing to obtain the impedance ventilation waveform. Then, 14 features were calculated from the ventilation waveform and fed to a random forest (RF) classifier to discriminate false positive detections from actual ventilations. The RF feature importance was used to determine the best feature subset for the classifier. The method was trained and tested using stratified 10-fold cross validation (CV) partitions. The training/test process was repeated 20 times to statistically characterize the results. The best ventilation detector had a median (interdecile range, IDR) F 1 -score of 96.32 (96.26-96.37). When used to provide feedback in 1-min intervals, the median (IDR) error and relative error in ventilation rate were 0.002 (-0.334-0.572) min -1 and 0.05 (-3.71-9.08)%, respectively. An accurate ventilation detector during mechanical CPR was demonstrated. The algorithm could be introduced in current equipment for feedback on ventilation rate and quality, and it could contribute to improve OHCA survival rates.

Importance: Emergency medical services (EMS) commonly perform endotracheal intubation (ETI) or insertion of supraglottic airways, such as the laryngeal tube (LT), on patients with out-of-hospital cardiac arrest (OHCA). The optimal method for OHCA advanced airway management is unknown., Objective: To compare the effectiveness of a strategy of initial LT insertion vs initial ETI in adults with OHCA., Design, Setting, and Participants: Multicenter pragmatic cluster-crossover clinical trial involving EMS agencies from the Resuscitation Outcomes Consortium. The trial included 3004 adults with OHCA and anticipated need for advanced airway management who were enrolled from December 1, 2015, to November 4, 2017. The final date of follow-up was November 10, 2017., Interventions: Twenty-seven EMS agencies were randomized in 13 clusters to initial airway management strategy with LT (n = 1505 patients) or ETI (n = 1499 patients), with crossover to the alternate strategy at 3- to 5-month intervals., Main Outcomes and Measures: The primary outcome was 72-hour survival. Secondary outcomes included return of spontaneous circulation, survival to hospital discharge, favorable neurological status at hospital discharge (Modified Rankin Scale score ≤3), and key adverse events., Results: Among 3004 enrolled patients (median [interquartile range] age, 64 [53-76] years, 1829 [60.9%] men), 3000 were included in the primary analysis. Rates of initial airway success were 90.3% with LT and 51.6% with ETI. Seventy-two hour survival was 18.3% in the LT group vs 15.4% in the ETI group (adjusted difference, 2.9% [95% CI, 0.2%-5.6%]; P = .04). Secondary outcomes in the LT group vs ETI group were return of spontaneous circulation (27.9% vs 24.3%; adjusted difference, 3.6% [95% CI, 0.3%-6.8%]; P = .03); hospital survival (10.8% vs 8.1%; adjusted difference, 2.7% [95% CI, 0.6%-4.8%]; P = .01); and favorable neurological status at discharge (7.1% vs 5.0%; adjusted difference, 2.1% [95% CI, 0.3%-3.8%]; P = .02). There were no significant differences in oropharyngeal or hypopharyngeal injury (0.2% vs 0.3%), airway swelling (1.1% vs 1.0%), or pneumonia or pneumonitis (26.1% vs 22.3%)., Conclusions and Relevance: Among adults with OHCA, a strategy of initial LT insertion was associated with significantly greater 72-hour survival compared with a strategy of initial ETI. These findings suggest that LT insertion may be considered as an initial airway management strategy in patients with OHCA, but limitations of the pragmatic design, practice setting, and ETI performance characteristics suggest that further research is warranted., Trial Registration: ClinicalTrials.gov Identifier: NCT02419573.

Aim: Current consensus guidelines for cardiopulmonary resuscitation (CPR) recommend that chest compressions resume immediately after defibrillation attempts and that rhythm and pulse checks be deferred until completion of 5 compression:ventilation cycles or minimally for 2min. However, data specifically confirming the post-shock duration of asystole or pulseless electrical activity before return of spontaneous circulation (ROSC) are lacking. Our aim was to describe the frequency of the various post-shock cardiac rhythms and the duration of post-shock pulselessness in out-of-hospital non-traumatic cardiac arrest., Method: Using prospectively-collected data from the Resuscitation Outcomes Consortium (ROC) Epistry database, the investigators reviewed monitor-defibrillator recordings of 176 patients who received defibrillation attempts in the out-of-hospital setting for ventricular fibrillation (VF) or ventricular tachycardia (VT) with absent pulses,., Results: Among 376 different defibrillation attempts delivered in the 176 patients, there were 182 resulting episodes of post-shock asystole. The mean interval of asystole after defibrillation was 69±136s (median 20s; IQR 36) and the mean interval for return of an organized rhythm was 64±157s (median 7s; IQR 26). The mean time to ROSC was 280±320s (median 136s; IQR 445)., Conclusion: After defibrillation attempts, the majority of patients remain pulseless for over 2min and the duration of asystole before return of pulses is longer than 120s beyond the shock gap in as many as 25%. These data support the recommendation to immediately resume chest compressions for 2min following attempted defibrillation., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Cardiopulmonary resuscitation (CPR) guidelines recommend the administration of chest compressions (CC) at a standardized rate and depth without guidance from patient physiologic output. The relationship between CC performance and actual CPR-generated blood flow is poorly understood, limiting the ability to define "optimal" CPR delivery. End-tidal carbon dioxide (ETCO2) has been proposed as a surrogate measure of blood flow during CPR, and has been suggested as a tool to guide CPR despite a paucity of clinical data. We sought to quantify the relationship between ETCO2 and CPR characteristics during clinical resuscitation care., Methods: Multicenter cohort study of 583 in- and out-of-hospital cardiac arrests with time-synchronized ETCO2 and CPR performance data captured between 4/2006 and 5/2013. ETCO2, ventilation rate, CC rate and depth were averaged over 15-s epochs. A total of 29,028 epochs were processed for analysis using mixed-effects regression techniques., Results: CC depth was a significant predictor of increased ETCO2. For every 10mm increase in depth, ETCO2 was elevated by 1.4mmHg (p<.001). For every 10 breaths/min increase in ventilation rate, ETCO2 was lowered by 3.0mmHg (p<.001). CC rate was not a predictor of ETCO2 over the dynamic range of actual CC delivery. Case-averaged ETCO2 values in patients with return of spontaneous circulation were higher compared to those who did not have a pulse restored (34.5±4.5 vs 23.1±12.9mmHg, p<.001)., Conclusions: ETCO2 values generated during CPR were statistically associated with CC depth and ventilation rate. Further studies are needed to assess ETCO2 as a potential tool to guide care., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Litter size and progeny birth weights are lower in gilts than in sows. Somatotropin (ST) is an important regulator of ovulation, fetal growth and survival. We therefore investigated effects of pST treatment of gilts for two to four weeks before mating on ovulation rate, behavioural estrus, fetal growth and survival, litter size and birth weights. In Experiment One, gilts were injected with 0, 30, 60 or 90 µg pST/kg/day for 14 days commencing 7 days after first estrus. Reproductive tracts were collected and corpora lutea and follicle numbers counted 5.5 days after second estrus. Ovulation rate (P=0.031) and number of medium-sized follicles (P=0.059) correlated positively with pST dose. In Experiment Two, gilts were injected with 0, 12.5, 25 or 50 µg pST/kg/day for 21 days from first estrus, and mated at second estrus. Numbers of corpora lutea, follicles and fetuses were counted at day 31 of pregnancy. Numbers of medium follicles and ovary weights were positively related to pST dose. In Experiment Three, 31 week old (1(st) replicate) or 27 week old (2(nd) replicate) gilts were injected daily with 0 or 12.5 µg pST/kg/day until mating 25.9 ± 0.6 days later, and delivered at term. Pre-mating pST increased total litter size in younger gilts in the 2(nd) replicate only (P<0.05). In conclusion, injecting gilts with pST before mating does not consistently alter ovulation rate, increases the number of medium follicles available for recruitment at the second mating after treatment and increases subsequent litter size in younger gilts.

Aims: The insulin-like growth factors (IGFs) are thought to contribute to glucose homeostasis. The aim of our study was to examine the response of the IGFs and their binding proteins to an intravenous load of glucose in a cohort of young men and women with normal glucose tolerance., Methods: The intravenous glucose tolerance test (IVGTT) was used to quantify insulin sensitivity and insulin secretion in 160 adults aged 20-21 years in Adelaide, Australia. Serum IGF-I, IGF-II, IGF-binding protein (IGFBP)-1 and IGFBP-3 were measured during the IVGTT., Results: Women were less insulin sensitive than men with higher fasting insulin (women 55.6 +/- 4.4, men 44.1 +/- 3.6 pmol L(-1), P = 0.001) and first phase insulin secretion (women 3490 +/- 286, men 3038 +/- 271 pmol L(-1) min, P = 0.042). Women showed lower fasting free IGF-I (women 0.29 +/- 0.02, men 0.36 +/- 0.02 mug L(-1), P = 0.004) but higher IGFBP-3 (women 46.3 +/- 0.53, men 43.3 +/- 0.58 mg dL(-1), P = 0.001) and higher IGFBP-1 concentrations (women 37.0 +/- 2.9, men 24.8 +/- 2.3 mug L(-1), P = 0.012). IGFBP-1 fell by 5 min and remained suppressed. IGFBP-3 and total IGF-I fell until 60 min rising again by 2 h. IGF and IGFBP values were all higher in women. IGFBP-1 showed a negative association with fasting and stimulated insulin concentrations in both genders. First phase insulin secretion however showed positive correlations with IGFBP-3 (r = 0.321, P = 0.004) and IGF-I (r = 0.339 P = 0.002) in men but not women., Conclusion: Our data show that IGFBP-1, IGFBP-3 and IGF-I show acute changes following a glucose load and there are marked gender differences in these responses.

Blood IGF-I concentrations are persistently elevated throughout pregnancy in humans and guinea pigs and may regulate substrate partitioning between mother and conceptus. In the guinea pig, liver and adipose tissue have recently been suggested to contribute to the increased levels of circulating IGF-I in mid-pregnancy, but whether this persists in late pregnancy in undernutrition is not known. Therefore the effect of pregnancy and undernutrition on circulating IGF-I and hepatic expression of IGF-I in late gestation in the guinea pig was examined. Female guinea pigs (Cavia porcellus) were fed ad libitum throughout pregnancy or 70% of ad libitum intake for 28 days prior to and throughout pregnancy (term is 69 d). Non-pregnant animals were maintained for 88 days on the same diets. Plasma IGF-I was measured by RIA after molecular sieving chromatography at low pH. Abundances of IGF-I and beta-actin mRNA in maternal liver were quantified by digoxigenin-ELISA after RT PCR. Late pregnancy increased both the concentration of IGF-I protein (p<0.001) in plasma and the relative abundance of liver IGF-I mRNA (p<0.001) in ad libitum fed, but not in feed restricted pregnant guinea pigs. The concentration of IGF-I protein in plasma correlated positively with the relative abundance of IGF-I mRNA in liver overall (p<0.002), suggesting the liver as a major source of endocrine IGF-I in late pregnant guinea pigs. This study demonstrates that hepatic expression of IGF-I remains elevated during late pregnancy in the well fed guinea pig, which is in contrast to that observed in other non-human species.

We investigated whether leptin can suppress the prepartum activation of the fetal hypothalamus-pituitary-adrenal (HPA) axis and delay the timing of parturition in the sheep. First, we investigated the effects of a 4-day intravascular infusion of recombinant ovine leptin (n = 7) or saline (n = 6) on fetal plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations, starting from 136 days gestation (i.e., at the onset of the prepartum activation of the fetal HPA axis. The effects of a continuous intrafetal infusion of leptin (n = 7) or saline (n = 5) from 144 days gestation on fetal plasma ACTH and cortisol concentrations and the timing of delivery were also determined in a separate study. There was an increase in fetal plasma ACTH (P < 0.01) and cortisol (P < 0.001) concentrations when saline was infused between 136-137 and 140-141 days gestation. Plasma ACTH and cortisol concentrations did not rise, however, when leptin was infused during this period of gestation. When leptin was infused after 144 days gestation, there was no effect of a 4- to 5-fold increase in circulating leptin on fetal ACTH concentrations. In contrast, leptin infusion from 144 days gestation suppressed (P < 0.05) fetal plasma cortisol concentrations by around 40% between 90 and 42 h before delivery. There was no difference, however, in the length of gestation between the saline- and leptin-infused groups (saline infused, 150.2 +/- 0.5 days; leptin infused, 149.8 +/- 1.0 days). In saline-infused fetuses, there was a significant negative relationship between the plasma concentrations of cortisol (y) and leptin (x) between 138 and 146 days gestation (y = 81.4 - 7.7x, r = 0.38, P < 0.005). This study provides evidence for an endocrine negative feedback loop between leptin and the HPA axis in fetal life.

Treatment of pigs with porcine ST (pST) in early to mid-pregnancy increases body weight and length of their fetuses by mid-pregnancy, but this increased weight may not persist to birth. We investigated the effects of short- (25 d) and long-term (75 d) treatment with pST, and interactions between long-term pST treatment and crude protein content of diet, in restricted-fed gilts. In both experiments, Large White x Landrace gilts were bred at first estrus to Large White x Duroc boars and allowed to farrow naturally. In the first experiment, gilts were fed 1.8 kg/d of a diet containing 13.5 MJ DE/kg of DM and 15.05% CP (as-fed basis) throughout pregnancy, and were injected daily with 0, 2, or 4 mg pST from d 25 to 50 of pregnancy. Maternal treatment with pST from d 25 to 50 of pregnancy did not affect the number of piglets born per litter or progeny size at birth. In the second experiment, gilts were injected daily with 0 or 2 mg of pST and fed 2.2 kg/d of a diet containing 14.5 MJ DE/kg and either (as-fed basis) 16.6% (0.81% lysine) or 22.2% CP (1.16% lysine) from d 25 to 100 of pregnancy. All gilts were then fed 3.0 kg/d of the lower protein diet from d 100 of pregnancy to farrowing. Treatment with 2 mg pST/d from d 25 to 100 of pregnancy increased live weight of all gilts during the treatment period (P = 0.016), but the change in maternal live weight from d 25 to 100 of pregnancy was only increased (P = 0.001) by pST in gilts fed the higher protein diet. Live weight of gilts 1 d after farrowing was increased by pST treatment (P = 0.007), but was not altered by protein content of diet during pregnancy. In gilts fed the lower protein diet, but not in those fed the higher protein diet, pST treatment decreased maternal backfat depth during treatment (P < 0.020) and 1 d after farrowing (P = 0.002). Treatment with pST during pregnancy did not affect the number of piglets born per litter but independently increased body weight by 11.6% (P < 0.001) and length by 3.4% (P = 0.005) of progeny at birth and decreased (P < 0.01) the negative effect of litter size on body weight at birth. We conclude that in feed-restricted gilts, fetal weight gains in response to 25 d of pST treatment before mid-pregnancy are not maintained to term but that treatment with pST during most of pregnancy increases progeny size at birth and reduces maternal constraint of fetal growth.

Maternal nutrition and growth hormone (GH) treatment during early- to mid-pregnancy can each alter the subsequent growth and differentiation of muscle in progeny. We have investigated the effects of varying maternal nutrition and maternal treatment with porcine (p) GH during the second quarter of pregnancy in gilts on semitendinosus muscle cross-sectional area and fibre composition of progeny, and relationships between maternal and progeny measures and progeny muscularity. Fifty-three Large White x Landrace gilts, pregnant to Large White x Duroc boars, were fed either 2.2 kg (about 35 % ad libitum intake) or 3.0 kg commercial ration (13.5 MJ digestible energy, 150 g crude protein (N x 6.25)/kg DM)/d and injected with 0, 4 or 8 mg pGH/d from day 25 to 50 of pregnancy, then all were fed 2.2 kg/d for the remainder of pregnancy. The higher maternal feed allowance from day 25 to 50 of pregnancy increased the densities of total and secondary fibres and the secondary:primary fibre ratio in semitendinosus muscles of their female progeny at 61 d of age postnatally. The densities of secondary and total muscle fibres in semitendinosus muscles of progeny were predicted by maternal weight before treatment and maternal plasma insulin-like growth factor-II during treatment. Maternal pGH treatment from day 25 to day 50 of pregnancy did not alter fibre densities, but increased the cross-sectional area of the semitendinosus muscle; this may be partially explained by increased maternal plasma glucose. Thus, maternal nutrition and pGH treatment during the second quarter of pregnancy in pigs independently alter muscle characteristics in progeny.

This study aimed to determine for the first time whether leptin can act to alter the structural and functional characteristics of adipose tissue before birth. Leptin (0.48 mg/kg/day) or saline was infused intravenously into fetal sheep for 4 days from either 136 or 137 days of gestation (term=147+/-3 days). Circulating leptin concentrations were increased approximately four- to fivefold by leptin infusion. Leptin infusion resulted in a significant increase in the proportion of smaller lipid locules present within fetal perirenal adipose tissue (PAT), and this was associated with a significant increase in the proportion of multilocular tissue and a significant decrease in the proportion and relative mass of unilocular tissue in fetal PAT. The relative abundance of leptin mRNA in fetal PAT was significantly lower in the leptin-infused group, and there was a positive correlation between the relative abundance of leptin mRNA and the proportion of unilocular adipose tissue in fetal PAT. The amount of uncoupling protein 1 tended to be higher (P=0.06) in leptin-infused compared with saline-infused fetuses. This is the first demonstration that leptin can act to regulate the lipid storage characteristics, leptin synthetic capacity, and potential thermogenic functions of fat before birth.

In bovine follicles 2-5 mm in diameter, two morphologically distinct types of healthy follicles and two types of atretic follicles have been described recently. Healthy follicles either have columnar basal granulosa cells with follicular basal lamina composed of many layers or 'loops' or they have rounded basal cells with a conventional single-layered, aligned follicular basal lamina. In atretic follicles, cell death either commences at the basal layer and progresses to the antrum (basal atresia) with macrophage penetration of the membrana granulosa or death progresses from the antrum in a basal direction (antral atresia). Little is known about how these different phenotypes develop. To determine whether insulin-like growth factor binding protein (IGFBP) levels in follicular fluid differ between these different types of follicles, we measured IGFBP levels in fluids from these follicles. A total of 61 follicles were assessed by light microscopy and characterized by morphological analysis as either healthy, with columnar or rounded basal granulosa cells, or as undergoing antral or basal atresia. The IGFBP concentration in the follicular fluid of individual follicles from the four groups (n = 12-20 per group) was identified by Western ligand blots using (125)I-insulin-like growth factor (IGF)-II as a probe. Insulin-like growth factor binding proteins 2, 3 (44 and 40 kDa), 4 (glycosylated and non-glycosylated) and 5 were observed. The levels (per volume of fluid) of IGFBPs 2, 4 and 5 were greater in atretic follicles than in healthy follicles. However, there were no statistical differences in levels of each IGFBP between either the two types of healthy follicle or between the two types of atretic follicles. Thus, IGFBP levels are not related to the different types of healthy or atretic follicles.

Maternal nutrient restriction and impaired fetal growth are associated with postnatal insulin resistance, hyperinsulinemia, and glucose intolerance in humans but not consistently in other species, such as the rat or sheep. We therefore determined the effect of mild (85% ad libitum intake/kg body wt) or moderate (70% ad libitum intake/kg body wt) maternal feed restriction throughout pregnancy on glucose and insulin responses to an intravenous glucose tolerance test (IVGTT) in the young adult guinea pig. Maternal feed restriction reduced birth weight (mild and moderate: both P < 0.02) in male offspring. Moderate restriction increased plasma glucose area under the curve (P < 0.04) and decreased the glucose tolerance index (K(G)) (P < 0.02) during the IVGTT in male offspring compared with those of mildly restricted but not of ad libitum-fed mothers. Moderate restriction increased fasting plasma insulin (P < 0.04, adjusted for litter size) and the insulin response to IVGTT (P < 0.001), and both moderate and mild restriction increased the insulin-to-glucose ratio during the IVGTT (P < 0.003 and P < 0.02) in male offspring. When offspring were classed into tertiles according to birth weight, glucose tolerance was not altered, but fasting insulin concentrations were increased in low compared with medium birth weight males (P < 0.03). The insulin-to-glucose ratio throughout the IVGTT was increased in low compared with medium (P < 0.01) or high (P < 0.05) birth weight males. Thus maternal feed restriction in the guinea pig restricts fetal growth and causes hyperinsulinemia in young adult male offspring, suggestive of insulin resistance. These findings suggest that mild to moderate prenatal perturbation programs postnatal glucose homeostasis adversely in the guinea pig, as in the human.

Restricting maternal nutrition before and throughout pregnancy in the guinea-pig restricts foetal growth in part by altering placental structural determinants of substrate transfer function. The insulin-like growth factors have been implicated in mediating these changes. To assess the role of IGF-I in placental adaptation to maternal undernutrition, we examined the associations of circulating IGF-I and IGF binding proteins -1, -3 and -4 in the mother with placental structural development. In both mid- and late pregnancy, maternal food restriction reduced maternal plasma IGF-I by 56 per cent (P<0.0005) and 50 per cent (P<0.0005) respectively, and plasma IGFBP-3 by 47 per cent (P=0.03) and 55 per cent (P=0.002), respectively. Maternal plasma IGFBP-4 was reduced by 45 per cent (P=0.041) in food restricted guinea-pigs in mid-pregnancy but not late in pregnancy, while IGFBP-1 was unaltered at both stages. Late in pregnancy, food restriction reduced the ratio of maternal circulating IGF-I to IGFBP-1 by 52 per cent (P=0.011) and increased the ratio of IGF-I to IGFBP-3 in maternal plasma by 10 per cent (P=0.011). The relationships between the maternal IGF axis and structural correlates of placental function were assessed using pooled data from both ad libitum fed and food restricted animals. In mid-pregnancy, the volume density of the maternal blood space in the placental labyrinth correlated positively with both maternal plasma IGF-I and IGFBP-3, while maternal blood space volume correlated negatively with maternal plasma IGFBP-1. In late pregnancy, placental weight correlated positively with both maternal plasma IGF-I and IGFBP-4, while the surface area of syncytiotrophoblast and weight of trophoblast correlated positively, and mean syncytiotrophoblast thickness negatively, with maternal plasma IGF-I. Late in pregnancy, the volume density and weight of syncytiotrophoblast, the surface density and total surface area of trophoblast and the volume of the maternal blood space each correlated positively, and syncytiotrophoblast thickness correlated negatively with maternal plasma IGFBP-3. Concomitantly, placental weight, placental diameter, placental volume, volume density and weight of syncytiotrophoblast, weight of foetal capillaries, syncytiotrophoblast surface density and total syncytiotrophoblast surface area in the placental labyrinth, each correlated positively with the ratio of IGF-I to IGFBP-1 in maternal plasma, while syncytiotrophoblast thickness correlated negatively with this ratio. In late pregnancy therefore, increased trophoblast abundance and placental vascularity, and a reduced barrier to diffusion between maternal and foetal blood, occurs in association with increased abundance of IGF-I and its major carrier, IGFBP-3, and a reduction in that of IGFBP-1 in maternal blood in the guinea-pig. This suggests that systemic IGF-I and modulation of its bioavailability by IGFBPs -1 and -3 within the mother may influence placental growth and differentiation in an endocrine fashion, particularly when nutrition is limited., (Copyright 2002 Elsevier Science Ltd.)

We have investigated the effects of maternal undernutrition during late gestation on maternal and fetal plasma concentrations of leptin and on leptin gene expression in fetal perirenal adipose tissue. Pregnant ewes were randomly assigned at 115 days of gestation (term = 147 +/- 3 days [mean +/- SEM]) to either a control group (n = 13) or an undernourished group (n = 16) that received approximately 50% of the control diet until 144-147 days of gestation. Maternal plasma glucose, but not leptin, concentrations were lower in the undernourished ewes. A significant correlation was found, however, between mean maternal plasma leptin (y) and glucose (x) concentrations (y = 2.9x - 2.4; r = 0.51, P < 0.02) when the control and undernourished groups were combined. Fetal plasma glucose and insulin, but not fetal leptin, concentrations were lower in the undernourished ewes, and no correlation was found between mean fetal leptin concentrations and either mean fetal glucose or insulin concentrations. A positive relationship, however, was found between mean fetal (y) and maternal (x) plasma leptin concentrations (y = 0.18x + 0.45; r = 0.66, P < 0.003). No significant difference was found in the relative abundance of leptin mRNA in fetal perirenal fat between the undernourished (0.60 +/- 0.09, n = 10) and control (0.70 +/- 0.08, n = 10) groups. Fetal plasma concentrations of leptin (y) and leptin mRNA levels (x) in perirenal adipose tissue were significantly correlated (y = 1.5x +/- 0.3; r = 0.69, P < 0.05). In summary, the capacity of leptin to act as a signal of moderate maternal undernutrition may be limited before birth in the sheep.

To determine if dietary protein supplementation in early pregnancy alters total circulating insulin-like growth factor (IGF) levels, genetically similar heifers were fed diets containing different levels of protein in the first and second trimesters of gestation. The groups were: low/low (L/L), fed a diet containing 7% crude protein (CP) per kg/DM (low protein) in the first and second trimesters; high/high (H/H), fed a diet containing 14% CP per kg/DM (high protein) in the first and second trimesters; low/high (L/H), fed low protein in the first trimester and high in the second trimester and vice versa for the high/low (H/L) group. At day 62 of gestation, there was a significant difference (P<0.01) in IGF I concentrations between the high and low protein groups (149 versus 119 ng/ml, S.E. 5.9). There was a strong effect (P<0.001) of protein levels in the second trimester on IGF I levels on days 119, 153, and 183 of gestation but not at day 257. Mean IGF I levels for high and low nutrition in the second trimester were 157 and 97 (S.E. 6.6) for days 119, 191, and 88 (S.E. 12.6) for days 153 and 160, and 67 (S.E. 7.7) for day 183. At day 257, there was a significant interaction (P<0.01) between treatments with the means being 98(ab), 110(b), 116(b) and 79(a gamma) (means followed by a letter in common do not differ significantly, P<0.05) (S.E. 7.5) for H/H, H/L, L/H, and L/L, respectively. There was a significant (P<0.05) effect of protein supplementation in the first trimester on calf IGF I levels at birth with means being 42 and 25 (S.E. 5.2) for high and low protein supplementation, respectively. There was a significant (P<0.01) effect of protein supplementation in second trimester upon IGF II levels and a significant (P<0.05) negative correlation between calf birth weight and IGF II levels.

Exogenous insulin-like growth factor (IGF)-I has been shown to increase growth rate in neonatal pigs while an analogue of IGF-I, long arginine (LR3) IGF-I, has been shown to be more potent than IGF-I in the rat. Therefore, two studies were conducted to determine whether IGF-I and LR3IGF-I increase growth in the artificially-reared neonatal pig. Expt 1 involved forty-two (2 kg initial weight) pigs infused with either control, IGF-I (2, 4 or 8 microg/h) or LR3IGF-I (2, 4 or 8 microg/h) infusions for 8 d. Pigs were weighed and then offered 1.7 MJ (gross energy) milk replacer/kg0.75 per d. Expt 2 involved eighteen pigs (2 kg initial weight) treated with control saline, IGF-I (8 microg/h) or LR3IGF-I (8 microg/h) infusions. After 9 d an additional pump was inserted to increase the infusion rates of each of the growth factors (16 microg/h) for a further 9 d. Cows' milk was provided ad libitum. In Expt 1 there was no overall effect of growth factors on daily weight gain or slaughter weight. However, milk intake was greater in pigs infused with growth factors (909 v. 867 g/d, P=0.027), with an apparently greater milk intake by the pigs infused with IGF-I compared with LR3IGF-I (920 v. 898 g/d, P=0.12). Infusion of LR3IGF-I decreased plasma IGF-I concentrations, but had no effect on plasma IGF-II concentrations. In Expt 2, neither IGF-I nor LR3IGF-I infusion had any effect upon daily weight gain over the first 9 d of the study. However, over the second 9 d of the study, daily weight gain was increased in LR3IGF-I-infused pigs (457 v. 386 g/d, P<0.01), but not in pigs infused with IGF-I (413 v. 386 g/d, P=0.15). Milk intake was not different during the first 9 d of the study but was significantly greater in pigs infused with growth factors over the second half of the study (3407 v. 2905 g/d, P<0.01). Plasma IGF-binding protein-3 concentrations were highly correlated (R=0.85) with average daily gain over the 3 d preceding blood sampling. In conclusion, exogenous IGF-I and particularly LR3IGF-I can increase growth rate and milk intake in artificially-reared pigs fed ad libitum but not in limit-fed piglets.

The aim of this study was to investigate how administration of IGF-I and IGF-II, during early to mid pregnancy, affects maternal growth and body composition as well as fetal and placental growth, in ad libitum fed, and in moderately, chronically food restricted guinea pigs. From day 20 of gestation, mothers (3-4 months old) were infused with IGF-I, IGF-II (565 microg/day) or vehicle for 17 days and then killed on day 40 of gestation. Maternal organ weights, fetal and placental weights were assessed. Treatment with IGFs did not alter body weight gain and had small effects on body composition in the mothers. Both IGF-I and IGF-II increased fetal and placental weights in ad libitum fed dams and IGF-I increased placental weight in food restricted dams. In conclusion, treatment with IGF-I during the first half of pregnancy stimulates placental growth in both ad libitum fed and food restricted guinea pigs without affecting maternal growth while fetal growth is stimulated by IGF treatment only in ad libitum fed animals., (Copyright 2001 Elsevier Science Ltd.)

In the adult, insulin-like growth factor I (IGF-I) increases glomerular filtration rate (GFR) and renal blood flow (RBF) during both acute and chronic treatment. To study its effects on the developing kidney, chronically catheterized fetal sheep (120 +/- 1 days gestation) were infused intravenously for up to 10 days with 80 microgram/h IGF-I (n = 5) or vehicle (0.1% BSA in saline, n = 6). In contrast to previous acute studies in adult rats and humans, after 4 h of IGF-I fetal GFR and RBF were unchanged. Fractional sodium reabsorption increased (P < 0.05). However, by 4 days, GFR per kilogram had risen by 35 +/- 13% (P < 0.05), whereas RBF remained unchanged. Tubular growth and maturation may have occurred, as proximal tubular sodium reabsorption increased by ~35% (P < 0.005). Therefore, despite a marked increase in filtered sodium (~30%, P < 0.05), fractional sodium reabsorption did not change. Although the effects of IGF-I on renal function were delayed, plasma renin activity and concentration were both elevated after 4 h and remained high at 4 days (P < 0.05). Despite this, arterial pressure and heart rate did not change. Kidneys of IGF-I-infused fetuses weighed ~30% more (P = 0.05) and contained ~75% more renin than control fetuses (P < 0.005). Thus, in the fetus, the renal effects of long-term IGF-I infusion are very different from the adult, possibly because IGF-I stimulated kidney growth.

Maternal feed restriction may restrict fetal growth in part indirectly by impairing placental functional development. Such actions could be mediated by the insulin-like growth factors (IGF), which are important modulators of placental growth and differentiation and more generally, are influenced by nutrient availability. While a role for the fetal IGF axis has been demonstrated, less is known of the influence, if any, of that in the mother. This study aimed to determine whether alterations in the maternal IGF axis and placental functional and structural development due to maternal food restriction are related. We therefore examined the associations between placental structural parameters, the ratios of maternal to fetal plasma glucose and fetal to maternal plasma urea concentration, and maternal circulating IGF-I, IGF-II and IGFBP-2 in ad libitum fed and food restricted (70-90 per cent of the ad libitum intake) pregnant guinea pigs. In mid-gestation, fetal weight (r = 0.65, P = 0.008, n = 17), volume of the maternal blood space (r = 0.58, P = 0.048, n = 17), and surface density of syncytiotrophoblast (r = 0.65, P = 0.023, n = 17), were positively correlated, and syncytiotrophoblast thickness was negatively correlated, with maternal plasma IGF-II concentration (r = -0.69, P = 0.014, n = 17). Late in gestation, fetal weight, placental weight and total exchange surface area in the placenta were each negatively correlated with maternal plasma IGFBP-2 concentration (all P < 0.01), while the arithmetic mean thickness of syncytiotrophoblast was positively correlated with maternal plasma IGFBP-2 concentration. Late in gestation, the ratio of maternal to fetal plasma glucose was positively correlated with fetal weight (r = 0.54, P = 0.038, n = 15) and the ratio of fetal to maternal plasma urea concentration was positively correlated with placental weight (r = 0.52, P=0.046, n=15). Maternal feed restriction reduced the ratio of maternal plasma IGF-II to IGFBP-2 in late gestation by 75 per cent (P = 0.001) and this ratio was positively correlated with fetal weight (r = 0.56, P = 0.01, n = 20), placental weight (r = 0.59, P = 0.006), placental diameter (r = 0.621, P = 0.003), placental volume (r = 0.57, P=0.009), weight of trophoblast (r = 0.51, P=0.037), weight of fetal capillaries (r = 0.49, P = 0.046), syncytiotrophoblast surface density (r = 0.611, P = 0.009) and negatively correlated with syncytiotrophoblast thickness (r = -0.55, P = 0.021). Our results suggest that in mid-pregnancy, maternal circulating IGF-II promotes placental structural development, while later in pregnancy, IGFBP-2 inhibits it, and their relative abundance and interaction strongly influences placental structure and function near term., (Copyright 2001 IFPA and Harcourt Publishers Ltd.)

The extent to which maternal nutrition influences fetal growth through effects on placental functional development is unclear. Poor maternal nutrition is a major cause of poor fetal growth which increases neonatal morbidity and mortality, and may also increase the risk of several adult-onset diseases. We have therefore characterized the ontogeny of structural determinants of function in the placenta in guinea-pigs fed ad libitum or food restricted from before and during pregnancy. Guinea-pigs were killed at days 30 and 60 (term=67 days) of pregnancy. In ad libitum fed animals, the surface density (surface area/g placental labyrinth), which is a measure of the convolution of the exchange surface, doubled, while total surface area increased 18-fold between mid and late gestation. Concomitantly, the arithmetic mean barrier thickness to diffusion across trophoblast decreased by 68 per cent. Late in gestation, food restriction reduced the proportion of the placenta devoted to exchange (labyrinth) by 70 per cent (P< 0.04) and the weight of the placental labyrinth by 45 per cent (P=0.001). Maternal food restriction also reduced the total placental surface area for exchange by 36 per cent at day 30 (P=0.02) and 60 per cent at day 60 (P< 0.0005) of gestation, and the surface density of trophoblast by 36 per cent at day 30 (P=0.01) and 29 per cent at day 60 (P=0.005) of gestation. The arithmetic mean barrier thickness for diffusion was increased by maternal food restriction at both gestational ages (day 30, +37 per cent, P=0.008, and day 60, +40 per cent, P=0.01). These findings suggest that maternal food restriction not only reduces fetal and placental weights, but also induces structural alterations in the placenta that indicate functional impairment beyond what would be expected for the reduction in its weight., (Copyright 2001 Harcourt Publishers Ltd.)

While it is known that treatment with insulin-like growth factor I (IGF-I) stimulates growth of the fetal kidney, nothing is known about the short term or long term effects of IGF-I on fetal renal function. To investigate the acute effects of IGF-I on fetal renal function and on the activity of the fetal renin-angiotensin system, studies were carried out in 12 chronically catheterized fetal sheep aged 120 +/- 1 days, before and during a 4 h I.V. infusion of IGF-I at 80 ug h-1. Seven control fetuses were infused over the same period with vehicle (0.1% bovine serum albumin in 0.15 M saline). IGF-I infusion increased plasma IGF-I concentrations by about 80%. There was a small fall in arterial PO2 (P < 0.01), arterial PCO2 increased (P < 0.05), plasma lactate levels increased (P < 0.01) and arterial pH fell (P < 0.05). Fractional bicarbonate reabsorption increased and bicarbonate excretion decreased (P < 0.05). Infusions of IGF-I had no sustained effect on fetal arterial pressure. Glomerular filtration rate (GFR) did not change significantly during IGF-I infusion, but renal blood flow (RBF) fell (P < 0.05). Therefore filtration fraction relative to control values increased (P < 0.05), suggesting that efferent arteriolar vasoconstriction had occurred. IGF-I infusion led to an antidiuresis (P < 0.01), a rise in urinary osmolality (P < 0.05) and a fall in free water clearance (P < 0.01). Since fetal PO2 fell, it is probable that these effects were mediated by arginine vasopressin. The excretion rates of sodium, chloride and phosphate were all reduced by 4 h of infusion (P < 0.05), because their fractional reabsorption rates were all increased (sodium, P < 0.01; chloride, P < 0.01; and phosphate, P < 0.05). Plasma renin concentration increased by 275 +/- 52% during infusion of IGF-I (P < 0.005). Plasma renin activity also increased (P < 0.005), while circulating angiotensinogen concentrations fell (P < 0.05). In the adult, IGF-I increases both RBF and GFR, enhances tubular reabsorption and stimulates the renin-angiotensin system. In the fetus, however, it decreased RBF and had no effect on GFR, but was associated with enhanced tubular function and intense stimulation of renin secretion. Some of these effects of IGF-I on fetal renal function may be involved in maturation of the kidney in preparation for life after birth.

We evaluate the performance of various commercially available InGaAs/InP avalanche photodiodes for photon counting in the infrared at temperatures that can be reached by Peltier cooling. We find that dark count rates are high, and this can partially saturate devices before optimum performance is achieved. At low temperatures the dark count rate rises because of a strong contribution from correlated afterpulses. We discuss ways of suppressing these afterpulses for different photon-counting applications.

Inhibition of insulin-like growth factor (IGF)-I induced DNA synthesis in bovine oocyte-cumulus complexes (OCCs) caused by follicle-stimulating hormone (FSH) has been linked to changes in the extracellular matrix which do not occur in mural granulosa cells (MGCs). We investigated regulation by IGF-I and FSH of secreted and extracellular matrix entrapped IGF-binding proteins. OCCs and MGCs from bovine ovaries were cultured in media supplemented with IGF-I and FSH for 24 h. Culture media and extracellular matrix were analysed for IGF-binding proteins by Western ligand blot and immunoblot and found to contain principally IGFBP-3 and -5. The combined treatment of IGF-I and FSH increased the concentration of IGFBP-3 in OCC and MGC conditioned media by 4- and 6-fold, respectively. Treatment of OCCs and not MGCs with IGF-I and FSH together increased extracellular matrix IGFBP-5 by 2.5-fold. The differential regulation of extracellular matrix IGFBP-5 in OCCs compared to MGCs suggest involvement of changes in the extracellular matrix brought about by IGF-I and FSH in overall regulation of IGF-I in the ovarian follicle.

Previous studies have reported conflicting data on gender differences in plasma IGF-I in postnatal pigs. There is also debate over the role of IGF-II in regulation of postnatal growth. We have, therefore, determined the concentrations of plasma IGF-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) in boars, barrows, and gilts and related these to postnatal growth characteristics. Plasma concentrations of IGF-I were higher in boars than in gilts or barrows from 13 wk. of age, and plasma IGF-II levels were generally higher in barrows than in boars or gilts. Plasma IGFBP-3 levels were higher in boars than in gilts or barrows at most ages. Between 15 and 23 wk. of age, IGF-I and IGFBP-3, but not IGF-II, were positively associated with growth rate, voluntary feed intake, and gain:feed ratio. Plasma IGF-II, but not IGF-I or IGFBP-3, was positively associated with backfat depth during this period. These results support the hypothesis that circulating IGF-I and IGF-II are regulators of lean and adipose tissue growth, respectively.

Insulin-like growth factor-1 (IGF-1) is perhaps the most important endogenous factor controlling growth. Most studies to date in livestock have shown that IGF-1 has greatest efficacy when animals are in a catabolic state. We have determined the effects of an i.v. infusion of the IGF-1 analog Long(R3)-IGF-1 on protein metabolism in beef heifers that were slowly losing liveweight because of restricted feeding. There was a tendency for both whole-body protein and skeletal muscle protein to be conserved in Long(R3)-IGF-1-treated heifers. Long(R3)-IGF-1 administration markedly reduced the plasma concentrations of all amino acids measured and glucose. There was a significant change in the profile differences of endogenous plasma IGF-1 concentrations during the 8-hr infusion period, with plasma IGF-1 decreasing sharply in the test group. There was a significant difference in mean profiles for plasma IGF-2 between the test and control groups. Overall, plasma IGF-2 for the control group decreased only slightly over time (about 40 ng/ml), whereas the test group decreased dramatically (by about 140 ng/ml). Increased plasma concentrations of a 31-32-kDa IGF-binding protein (possibly IGF-binding protein-1) in the treated group was detected by radioligand blot. We found that Long(R3)-IGF-1 infusion tended to preserve whole-body and muscle protein in beef heifers on a low-quality diet, and suggest that further investigation of this treatment may provide an alternative approach to reducing weight loss during the dry season.

The growth rate of the young pig is generally much less than its potential and may be constrained by endocrine status as well as by nutrient intake. The aim of this study was to determine whether porcine somatotropin (pST) could increase growth in the nursing pig. Fourteen sows nursing litters of 6 (n = 7) or 12 (n = 7) piglets were utilized to establish a high and low plane of nutrition for sucking pigs. On Day 4 of lactation, the median two male pigs from each litter were randomly allocated to one of two doses of pST (0 or 60 micrograms/kg/d) until weaning on Day 31. Pigs were bled on Days 4, 13, 22, and 31 of lactation and the plasma was analyzed for insulin-like growth factor (IGF)-I, IGF-II, and IGF binding protein-3 (IGFBP-3). Pigs were weaned into conventional accommodation and further weighed on Days 63, 91, and 119. Pigs from litters of 6 grew more quickly and weighed 2.2 kg (P = 0.01) and 3.5 kg (P = 0.04) more than pigs from litters of 12 at 31 and 63 d of age, respectively. There was no effect of pST on preweaning growth of sucking pigs (261 vs. 258 g/d, P = 0.68), although growth rate increased in the final 3 d before weaning at 31 d (241 vs. 294 g/d, P = 0.01). IGFBP-3 was greater (1.09 vs. 0.78 micrograms/ml, P < 0.001), whereas IGF-I tended to be greater (206 vs. 176 ng/ml, P = 0.14), in pigs from the small litters. There was no effect of pST on plasma IGF-I (182 vs. 195 ng/ml, P = 0.454) or IGFBP-3 (0.93 vs. 0.94 microgram/ml, P = 0.85) concentrations. Plasma IGF-I and IGFBP-3 were highly correlated with the growth rate of nursing pigs (R = 0.638 and 0.756, respectively). There were no effects of pST (340 vs. 328 ng/ml, P = 0.48) or litter size (336 vs. 333 ng/ml, P = 0.88) on IGF-II. In conclusion, pST had no little or no effect on growth performance or plasma IGF-I, IGF-II, or IGFBP-3 in sucking pigs on either a high or low plane of nutrition.

The effect of moderate food restriction on pregnancy-associated changes in weight gain, body composition, and circulating insulin-like growth factors (IGF) I and II and IGF-binding proteins (IGFBP)-1 through-4 and their relationship was determined in the guinea pig. Pregnancy did not stimulate weight gain but reduced fat deposition in ad libitum-fed animals and increased weight gain and fat deposition in food-restricted animals relative to their respective virginal group. Pregnancy increased the abundance of circulating IGF-I regardless of food intake and increased that of IGF-II in food-restricted animals only. Pregnancy also increased circulating IGFBP-1 and -2 in ad libitum-fed and food-restricted animals and IGFBP-4 in ad libitum-fed animals. Multiple regression analysis showed that maternal weight gain was negatively associated with circulating IGF-II and IGFBP-2. Fetal weight was positively associated with maternal circulating IGF-II and negatively associated with maternal circulating IGFBP-1 and -2. Significant interactions indicate, however, that the role of IGF-II and IGFBP-1 on fetal growth is dependent on the nutritional status of the mother.

Fetuses swallow large volumes of amniotic fluid. Absence of swallowing results in gastrointestinal tract (GIT) growth deficits. While it is not yet known to what extent the growth factors present in amniotic fluid are involved in GIT ontogeny, milk-derived growth factors are considered to be important for neonatal growth. Our experiment tested the hypothesis that a luminal growth factor (insulin-like growth factor-I, IGF-I) can sustain or promote GIT growth in utero in a model of gastrointestinal tract growth retardation. Ten-day infusion of either human recombinant IGF-I or vehicle into twin fetal sheep at 80 days gestation via an indwelling esophageal catheter resulted in altered GIT growth. Weight of the forestomach and small intestine increased. Significant histological changes were noted in the proximal small intestine, i.e. the region most exposed to the luminal infusion. Mucosal tissues were reduced in size. While the enterocytes in the proximal small intestine were generally more mature with regard to the ontogeny of the apical endocytic complex (which is responsible for uptake and transport of whole peptides), there were also many abnormal cytological features present. These included the development of large lysosomal-like inclusion bodies and many surfactant-like particles within the apical cytoplasm. Plasma IGF-I levels were on average 20% higher in treated siblings, suggesting that luminal IGF-I crossed the fetal gut and entered blood. IGF-II levels were not significantly affected. These observations are consistent with the suggestion that growth factors, which are present in swallowed amniotic fluid, influence fetal ontogeny.

Liver contains the highest concentrations of insulin-like growth factor (IGF) I mRNA in adult rats and sheep and is a major source of circulating IGF-I. In rats, inhibition of hepatic IGF-I production by exogenous IGF-I has been reported. In fetal sheep, skeletal muscle and liver are major sites of IGF-I synthesis and potential sources of circulating IGF-I. To determine whether feedback inhibition of IGF gene expression in fetal liver or muscle by IGF-I occurs, IGF-I and IGF-II mRNAs were measured in these tissues after intravenous infusion of recombinant human IGF-I into fetal sheep. Infusion of IGF-I (26 +/- 4 micrograms.h-1.kg-1; n = 6) or saline (n = 6) commenced on day 120 of pregnancy (term = 150 days) and continued for 10 days. Plasma concentrations of IGF-I were threefold higher in infused fetuses at 130 days of gestation (P < 0.0003), whereas those of IGF-II were unchanged. IGF-I infusion reduced the relative abundance of IGF-I mRNA (P < 0.0002) and IGF-II mRNA (P < 0.01) in fetal liver by approximately 50% but did not alter IGF-I or IGF-II mRNA in skeletal muscle. These results indicate that IGF-I inhibits the expression of both IGF-I and IGF-II genes in fetal liver and that IGF gene expression in fetal liver and muscle is differentially regulated by IGF-I.

We infused recombinant human insulin-like growth factor I (IGF-I) for 4 h at 12.3 micrograms.h-1.kg live weight-1 directly into the left femoral artery and measured the rates of synthesis, degradation, and gain of protein by the treated and contralateral limbs of well-fed (n = 8), feed-restricted (n = 10), and fasted (n = 9) castrated male lambs. Reducing feed intake decreased net protein gain of hindlimb muscle, reduced hindlimb glucose uptake, and lowered arterial plasma concentrations of IGF-I, insulin, glucose, phenylalanine, tyrosine, and isoleucine. The effect of nutrition on IGF-binding proteins (IGFBP) was generally small; IGFBP-2 was more abundant in fasted lambs. Infusion of IGF-I into the left femoral artery increased plasma levels of IGF-I 2- to 4-fold in the left femoral vein and by 1.5- to 3-fold in the artery and right femoral vein. In the treated limb, IGF-I reduced protein degradation, increased protein gain, and increased glucose uptake without altering blood flow or oxygen uptake, regardless of feed intake. Systemically, IGF-I reduced plasma insulin, phenylalanine, tyrosine, isoleucine, and leucine in all nutrition groups. Plasma IGFBP-3 was increased by 4 h of IGF-I treatment in fasted but not in fed lambs. In fed but not fasted lambs, IGF-I increased blood glucose concentration. Effects of IGF-I on protein metabolism in the contralateral limb were affected by nutrition, generally more so in fasted than in unrestricted fed lambs.

The effects of sex and age on patterns of circulating somatotropin (ST) concentration and plasma IGF-I, IGF-II, insulin, and IGF binding protein-3 (IGFBP-3) were studied in ram, wether, and ewe lambs (n = 7 or 8) sampled at mean ages of 81 (I1) and 158 d (I2). Between 81 and 158 d of age, rams grew more rapidly than wethers (P < .01), and wethers grew more rapidly than ewes (P < .01). The sex differences in growth were reflected in empty body weight at slaughter: rams > wethers > ewes (P < .05). Mean plasma ST concentrations, ST pulse amplitude, and integrated plasma ST concentrations were greater (P < .05) in rams than in ewes at I1 and I2. Characteristics of the ST plasma profile in wethers were generally intermediate between those of rams and ewes. The interpulse interval was greater in ewes than in wethers at I2. The IGF-I and IGFBP-3 concentrations were greater in rams than in ewes at both sampling times. Plasma IGF-II was greater in ewes than in rams at I2. Mean plasma ST was approximately two thirds less at I2 than at I1 regardless of sex. Mean plasma ST and IGF-I at both ages were positively correlated with growth. Mean plasma ST at I2 was negatively correlated with fatness at slaughter. Sex and age significantly affected patterns of circulating ST and concentrations of IGF-I and IGFBP-3 in prepubertal growing lambs, under conditions for which growth rates and composition were also sexually dimorphic.