1,720,968 research outputs found
The effect of birth weight on hypothalamo-pituitary-adrenal axis function in juvenile and adult pigs
No full textProgramming of the hypothalamo-pituitary-adrenal (HPA) axis during prenatal and early postnatal life may explain, in part, the association between low birth weight (BW) and the increased incidence of cardiovascular and metabolic disease in later life. This study examined the effect of natural variations in BW on HPA axis function in juvenile and adult pigs. Low (< 1.47 kg) and high (> 1.53 kg) BW pure-bred Large White piglets from 15 litters were studied at 3 (n = 47) and 12 (n = 17) months of age. At each age, HPA axis function was tested by hypoglycaemic challenge (I.V. insulin; 0.5 IU (kg body weight)-1) and ACTH challenge (I.V. Synacthen, 2 µg (kg body weight)-1). At 3 months of age, adrenal size, the ratio of adrenal cortical to medullary area and stimulated cortisol concentrations were elevated in pigs that were of low BW and that remained small after birth. At 12 months of age, thinness at birth was associated with elevated adrenal responsiveness to insulin-induced hypoglycaemia. These results are consistent with the hypothesis that impaired fetal and early postnatal growth are associated with altered HPA axis function in later life
Insulin sensitivity in juvenile and adult large white pigs of low and high birthweight
No full textAims/hypothesis We have previously demonstrated poor glucose tolerance in adult pigs of naturally occurring low birthweight. The aim of this study was to examine sensitivity to insulin in juvenile (3-month-old) and adult (12-month-old) pigs of low and high birthweight.Methods Low (<1.47 kg) and high (>1.53 kg) birthweight piglets from 15 litters were studied at 3 (n=47) and 12 (n=17) months of age. At each age the selected pigs were tranquilised and catheters were inserted into the dorsal aorta and caudal vena cava under general anaesthesia. After recovery, insulin sensitivity was measured as the glucose decrement (mmol·l–1·min–1) during the first 10 min after an intravenous insulin bolus (0.5 IU/kg). Data (means ± SEM) were analysed by the Student's t test, ANOVA and linear regression.Results The body weight of low birthweight female, but not male, pigs remained smaller than that of high birthweight pigs at 3 and 12 months of age. At 3 months, thinness at birth and rapid catch-up growth in the first month of life were associated with increased insulin sensitivity in males. In females thinness at 3 months was associated with reduced sensitivity to insulin. At 12 months, early postnatal catch-up growth was associated with insulin resistance, irrespective of sex, when all data were combined.Conclusions/interpretation The glucose intolerance previously observed in young adult pigs of low birthweight is probably due to insulin resistance. Early catch-up growth in low birthweight pigs was the clearest predictor of adult insulin resistance
The effects of birth weight and postnatal growth patterns on fat depth and plasma leptin concentrations in juvenile and adult pigs
No full textLow birth weight is associated with altered adipose tissue deposition and regulation of leptin production. This study determined the effects of naturally occurring variations in birth weight in pigs on postnatal growth patterns, body fat depth and plasma leptin and other hormone concentrations. Low (< 1.47 kg) and high (> 1.53 kg) birth weight piglets were studied at 3 months (juvenile; n= 47) and 12 months of age (young adult; n= 17). At each age, arterial and venous catheters were inserted under general anaesthesia. Plasma leptin, cortisol, glucose, insulin and catecholamine concentrations were determined in basal blood samples. Body fat depth was measured by ultrasound at 12 months of age. Overall, adult fat depth was greater in low compared to high birth weight pigs and increased fat depth was associated with thinness at birth and poor early growth rates. These effects were strongest in females. Fat depth was related to current weight only in males. Compared to high birth weight pigs, plasma leptin concentrations were reduced in low birth weight females at 3 months and in low birth weight males at 12 months of age. This study demonstrates sex-specific effects of low birth weight on postnatal growth and body fatness and on plasma leptin concentrations in pigs
Adrenal responsiveness and the timing of parturition in hypothalamo-pituitary disconnected ovine foetuses with and without constant adrenocorticotrophin infusion
No full textOvine parturition results from an increase in foetal cortisol secretion in late gestation which is dependent on an intact hypothalamo-pituitary connection. The cortisol surge and parturition fails in hypothalamo-pituitary disconnected (HPD) foetuses but, paradoxically, immunoreactive (ir)-ACTH concentrations and secretory dynamics appear normal. This study compares the occurrence and timing of labour, basal ir-ACTH and cortisol concentrations and adrenal responsiveness in HPD foetuses (HPD/ACTH) receiving constant ACTH(1-24) infusion (43 ng/h/kg) from surgery (114+/-1 days gestational age (GA)) with those of saline-infused HPD or intact foetuses (HPD/SAL and INT/SAL). HPD/ACTH foetuses initiated labour at 147+/-2 days GA, which was not significantly different from INT/SAL foetuses (149+/-1 day GA). HPD/SAL foetuses were killed electively at 146+/-3 days GA with no signs of labour. Foetal ir-ACTH concentrations in all groups were indistinguishable, but only HPD/ACTH and INT/SAL foetuses had a significant cortisol surge. Adrenal responsiveness to ACTH(1-24)(1 microg/kg) was greater in HPD/ACTH foetuses than in HPD/SAL or INT/SAL foetuses at all GAs studied. Adrenal responsiveness in HPD/SAL foetuses exceeded that in INT/SAL foetuses at 120 and 130 days GA but did not change with GA. In summary, the basal cortisol and parturition defect in HPD foetuses was reversed by low-dose ACTH(1-24) infusion. Basal cortisol concentrations were unrelated to adrenal responsiveness. HPD/SAL foetuses had hyper-responsive adrenals compared to those of INT/SAL foetuses until 130 days GA, suggesting that the foetal hypothalamus exerts a negative influence on adrenal cortisol responses before 130 days GA, after which time stimulatory influences predominate.</p
Developmental origins of the metabolic syndrome: body clocks and stress responses
No full textThe prevalence of the metabolic syndrome, which represents a spectrum of metabolic and cardiovascular disorders, continues to increase at an alarming rate in contemporary society. Inadequate responses of an individual to environmental challenges such as unbalanced diet or lack of physical exercise during their life course has been recognised to increase risk of this pathological condition. Recent evidence suggests that this may involve alterations in the settings of the circadian clock system, which consists of oscillating molecular pacemakers found not only in the hypothalamic region of the brain but also in most peripheral tissues, and of the hypothalamic–pituitary–adrenal (HPA) axis which regulates stress responses. These two systems are now known to interact to produce an integrated response to environmental challenges. In this review, we highlight the importance of environmental cues during early development in establishing the homeostatic set-points of the circadian clock and HPA stress systems. These effects can operate within the normal range and are not in themselves pathological, but can nevertheless affect an individual’s response to environmental challenges in adult life and thus their risk of the metabolic syndrome.<br/
Sex and twinning influence early gestation undernutrition effects on sheep offspring growth
No full textObjectives: Multiple pregnancy affects size at birth and
growth pattern from as early as 8 weeks gestation (Iffy et
al., 1983. Am. J. Obstet. Gynecol. 146, 970—972). Male
embryos grow at a greater rate than females (Pedersen,
1980. Br. Med. J. 281, 1253). We hypothesised that
moderate maternal undernutrion in early gestation will
have a greater effect on male offspring growth, particularly
if combined with the increased constraint of being a twin.
Methods: Welsh Mountain ewes received 100% (C, n =41) or
50% nutrient requirements (U, n =47) from 1 to 31 days
gestation (dGA), and 100% thereafter. Ewes were weighed
weekly and blood samples were collected at 1, 30, and 65
dGA for cortisol analysis (Immulite analyser, DPC).
Results: At day 31, U ewes had gained less weight than C
ewes and had a lower plasma cortisol concentration
( p b0.05). During 1—31 dGA, twin bearing ewes gained less
weight than singleton bearing ewes. At birth, twins were
smaller than singleton lambs ( p b0.05). Weight gained
between birth and 12 weeks old and weight at 12 weeks
old were greater in U males compared to C males, an effect
that was predominantly in twins ( p b0.01). Data were
analysed by ANOVA.
Conclusion: The increased constraint of being a twin and a
male embryo in a nutrient-restricted intrauterine environment
induces a phenotype more likely to gain weight in a
good postnatal environment.
Supported by the British Heart Foundation
The role of the pituitary gland and ACTH in the regulation of mRNAs encoding proteins essential for adrenal steroidogenesis in the late-gestation ovine fetus
No full textTo further understand the relative roles of the pituitary gland and ACTH in the regulation of mRNAs encoding proteins that are essential for adrenal development, we investigated the effects of, first, an ACTH infusion and labour in intact fetuses and, secondly, the effect of an ACTH infusion to fetuses with and without a pituitary gland, on the relative abundance of the mRNA encoding for the ACTH receptor (MC2R), steroidogenic factor 1 (SF-1), cholesterol side-chain cleavage enzyme (P450(scc)), 3beta-hydroxysteroid dehydrogenase (3betaHSD) and 17alpha-hydroxylase (P450(C17)) in the fetal adrenal gland. ACTH(1-24) infusion (14.7 pmol/kg per h) to intact fetuses was without effect on the abundance of mRNA encoding MC2R and SF-1, irrespective of whether the infusion was given for 18 (115-132 days of gestation) or 32 days (115 days to term (147 days of gestation)). Hypophysectomy (HX) did not alter the expression of MC2R mRNA; however, the abundance of SF-1 mRNA fell by approximately 50% following the removal of the pituitary gland. ACTH(1-24) infusion to HX fetuses failed to restore levels of SF-1 mRNA to that seen in intact animals. P450(scc) and 3betaHSD mRNAs were increased by ACTH(1-24) infusion for 18 days in intact animals, although no effects of the infusion were seen on P450(C17) mRNA levels. For all three of these mRNAs, there was a significant increase in their abundance between 132 days of gestation and term in intact fetuses. By term, ACTH(1-24) infusion was without any additional effect on their abundance. HX decreased the expression of P450(scc), 3betaHSD and P450(C17) mRNAs, while ACTH(1-24) infusion to HX fetuses increased the expression of these mRNAs to levels seen in intact animals. There were significant correlations between the abundance of the mRNA for P450(scc), 3betaHSD and P450(C17), but not MC2R and SF-1, and premortem plasma cortisol concentrations. These results emphasise the importance of the pituitary gland and ACTH in the regulation of the enzymes involved in adrenal steroidogenesis. Factors in addition to ACTH may also play some role, as the infusion was not always effective in increasing the abundance of the mRNAs. Surprisingly, the mRNA for MC2R and SF-1 did not appear to be regulated by ACTH in the late-gestation ovine fetus, though a pituitary-dependent factor may be involved in the regulation of SF-1 mRNA abundance
Hypothalamo-pituitary-adrenal axis responsiveness in adult sheep following early life nutrient restriction
No full textStudies on the role of ACTH in the regulation of adrenal responsiveness and the timing of parturition in the ovine fetus
No full textA dramatic late-gestation increase in fetal plasma cortisol concentrations is critical for the timing of parturition in the sheep. This increase appears to depend upon an intact hypothalamo-pituitary unit and is characterised by increasing responsiveness of the fetal adrenal gland to ACTH. ACTH has been postulated as the critical determinant of the late-gestation cortisol increase; however, recent evidence has suggested that other factors, including the ACTH precursor, pro-opiomelanocortin, may also be involved. To further define the role of ACTH in determining the timing of parturition and the responsiveness of the fetal adrenal gland, intact (INT/ACTH) and hypophysectomised (HX/ACTH) fetuses received a continuous infusion of ACTH(1-24) from the time of surgery (approximately 115 days gestational age (GA)) at a rate we have previously shown to generate normal fetal cortisol concentrations and term parturition in HX fetuses. A third group of saline-infused intact fetuses (INT/SAL) served as the control group. Adrenal responsiveness was assessed by cortisol responses to ACTH(1-24) challenges at 120, 130 and 140 days GA. There were no differences between the three groups of fetuses in the timing of parturition, the late-gestation increase in cortisol concentrations or the size of the adrenal cortex. In both INT/SAL and INT/ACTH fetuses, there were significant increases in basal immunoreactive-ACTH concentrations with advancing GA, although no such increase was observed in HX/ACTH fetuses. The proportion of total ACTH immunoreactivity present in low molecular weight (LMW) forms in INT/ACTH fetuses was greater than that in INT/SAL fetuses, while the level of LMW ACTH in HX/ACTH fetuses was intermediate. Both ACTH(1-24)-infused groups of fetuses had dramatically enhanced adrenal responsiveness to ACTH(1-24) at all GAs tested when compared with INT/SAL fetuses and there was a correlation (in rank order) between the proportion of LMW ACTH immunoreactivity and adrenal responsiveness. From these observations it appears that there is a separate regulation of adrenal responsiveness from basal cortisol concentrations and that an increase in basal cortisol concentrations can occur in the absence of an increase in basal ACTH concentrations. Furthermore, an increase in adrenal responsiveness does not appear to predict the timing of parturition nor basal cortisol concentrations. Taken together with previous studies it appears that ACTH plays an essential role in maintaining the growth of the fetal adrenal and enhancing its responsiveness, but a late-gestation increase in ACTH concentrations is not required to regulate basal cortisol concentrations or the timing of parturition.</p
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