scholarly journals Prolactin, prolactin receptor and uncoupling proteins during fetal and neonatal development

2003 ◽  
Vol 62 (2) ◽  
pp. 421-427 ◽  
Author(s):  
S. Pearce ◽  
A. Mostyn ◽  
M. C. Alves-Guerra ◽  
C. Pecqueur ◽  
B. Miroux ◽  
...  
Keyword(s):  
Short Form ◽  
Prolactin Receptor ◽  
Uncoupling Proteins ◽  
Late Gestation ◽  
Postnatal Life ◽  
Inner Mitochondrial Membrane ◽  
Fetal Sheep ◽  
Acute Response ◽  
Brown Adipose ◽  
Colonic Temperature

Uncoupling proteins (UCP) 1 and 2 are members of the subfamily of inner mitochondrial membrane carriers. UCP1 is specific to brown adipose tissue (BAT), where it is responsible for the rapid production of heat at birth. In fetal sheep UCP1 is first detectable at approximately 900d of gestation; its abundance increases with gestational age and peaks at the time of birth. The mRNA and protein for both the long and short form of the prolactin (PRL) receptor (PRLR) are also highly abundant in BAT. Enhanced PRLR abundance in late gestation is associated with an increase in the abundance of UCP1. This relationship between PRLR and UCP is not only present in BAT. Similar findings are now reported in the pregnant ovine uterus, where PRLR abundance reaches a maximum just before that of UCP2. However, the role of PRLR in BAT remains undetermined. Rat studies have shown that PRL administration throughout pregnancy results in offspring with increased UCP1 at birth. Studies in newborn lambs have shown that administration of PRL (20mg/d) causes an acute response, increasing colonic temperature in the first hour by 1°. This increased colonic temperature is maintained for the first 240h of life, in conjunction with enhanced lipolysis. After 70d of treatment there is no difference in the abundance of UCP1 but an increase in UCP1 activity; this effect may be mediated by an increase in lipolysis. Taken together these findings suggest that PRL could be an important endocrine factor during pregnancy and early postnatal life.

Fetal and neonatal adipose maturation: a primary site of cytokine and cytokine-receptor action

2001 ◽  
Vol 29 (2) ◽  
pp. 80-85 ◽  
Author(s):  
T. Stephenson ◽  
H. Budge ◽  
A. Mostyn ◽  
S. Pearce ◽  
R. Webb ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Maternal Nutrition ◽  
Short Form ◽  
Uncoupling Protein ◽  
Prolactin Receptor ◽  
Late Gestation ◽  
Metabolic Adaptation ◽  
Postnatal Life ◽  
Brown Adipose

During late gestation, the maturation of fetal adipose tissue is geared towards the synthesis of high levels of uncoupling protein 1 (UCP1), which is unique to brown adipose tissue. At birth, rapid activation of UCP1 ensures a large increase in heat production. These adaptations are nutritionally sensitive, and may be mediated in part by rapid changes in prolactin and leptin secretion after birth. Restriction of maternal nutrition reduces adipose tissue deposition, with no effect on UCP1. Increased maternal food intake results in increases in levels of UCP1 and the short form of the prolactin receptor, but in a decrease in adipose tissue content per kg of fetus. The ontogeny of the long and short forms of the prolactin receptor follows that of UCP1, to peak at birth. Then, during postnatal life, UCP1 disappears in parallel with the loss of prolactin receptors. Treatment of neonatal lambs with prolactin increases body temperature and the thermogenic potential of brown adipose tissue. In contrast, acute leptin treatment results in maintenance of colonic temperature, but chronic leptin treatment accelerates UCP1 loss. Increasing our understanding of the interaction between prolactin and leptin during perinatal development may enable the establishment of strategies aimed at maximizing adipose tissue development in order to promote metabolic adaptation to the extra-uterine environment.

Cortisol has no effect on prolactin receptor (PRLR) abundance in brown adipose tissue (BAT) in late gestation fetal sheep

2001 ◽  
Vol 29 (1) ◽  
pp. A39-A39
Author(s):  
S. Pearce ◽  
H. Budge ◽  
A. Forhead ◽  
A. Fowden ◽  
P. Ingleton ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Prolactin Receptor ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Brown Adipose

scholarly journals Genomics of estradiol-3-sulfate action in the ovine fetal hypothalamus

2012 ◽  
Vol 44 (13) ◽  
pp. 669-677 ◽  
Author(s):  
Maria Belen Rabaglino ◽  
Elaine Richards ◽  
Nancy Denslow ◽  
Maureen Keller-Wood ◽  
Charles E. Wood
Keyword(s):  
Feeding Behavior ◽  
Transforming Growth Factor ◽  
Fetal Brain ◽  
Ovis Aries ◽  
Late Gestation ◽  
Postnatal Life ◽  
Growth Factor Signaling ◽  
Fetal Sheep ◽  
Ovine Fetal ◽  
Agouti Related Protein

In fetal sheep during late gestation sulfoconjugated estrogens in plasma reach a concentration 40–100 times greater than unconjugated estrogens. The objective of the present study was to determine the genomics of estradiol-3-sulfate (E2S) action in the ovine fetal brain. The hypothesis was that E2S stimulates genes involved in the neuroendocrine pathways that direct or facilitate fetal development at the end of gestation. Four sets of chronically catheterized ovine twin fetuses were studied (gestational age: 120–127 days gestation) with one infused with E2S intracerebroventricularly (1 mg/day) and the other remaining untreated (control). After euthanasia, mRNA samples were extracted from fetal brains. Only hypothalamic samples were employed for this study given the important function of this brain region in the control of the hypothalamus-pituitary-adrenal axis. Microarray analysis was performed following the Agilent protocol for one-color 8 × 15 microarrays, designed for Ovis aries. A total of 363 known genes were significantly upregulated by the E2S treatment ( P < 0.05). Network and enrichment analyses were performed using the Cytoscape/Bingo software, and the results validated by quantitative real-time PCR. The main overrepresented biological processes resulting from this analysis were feeding behavior, hypoxia response, and transforming growth factor signaling. Notably, the genes involved in the feeding behavior (neuropeptide Y and agouti-related protein) were the most strongly induced by the E2S treatment. In conclusion, E2S may be an important component of the mechanism for activating orexigenic, hypoxia responsiveness and neuroprotective pathways in the lamb as it approaches postnatal life.

scholarly journals Genomic Effect of Triclosan on the Fetal Hypothalamus: Evidence for Altered Neuropeptide Regulation

Endocrinology ◽  
2016 ◽  
Vol 157 (7) ◽  
pp. 2686-2697 ◽  
Author(s):  
Maria Belen Rabaglino ◽  
Eileen I. Chang ◽  
Elaine M. Richards ◽  
Margaret O. James ◽  
Maureen Keller-Wood ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Fetal Brain ◽  
Late Gestation ◽  
Gene Set Enrichment Analysis ◽  
Postnatal Life ◽  
Fetal Life ◽  
Low Doses ◽  
Fetal Sheep ◽  
Reproductive Process

Triclosan (TCS), an antibacterial compound commonly added to personal care products, could be an endocrine disruptor at low doses. Although TCS has been shown to alter fetal physiology, its effects in the developing fetal brain are unknown. We hypothesize that exposure to TCS during fetal life could affect fetal hypothalamic gene expression. The objective of this study was to use transcriptomics and systems analysis to identify significantly altered biological processes in the late gestation ovine fetal hypothalamus after direct or indirect exposure to low doses of TCS. For direct TCS exposure, chronically catheterized late gestation fetal sheep were infused with vehicle (n = 4) or TCS (250 μg/d; n = 4) iv. For indirect TCS exposure, TCS (100 μg/kg · d; n = 3) or vehicle (n = 3) was infused into the maternal circulation. Fetal hypothalami were collected after 2 days of infusion, and gene expression was measured through microarray. Hierarchical clustering of all samples according to gene expression profiles showed that samples from the TCS-treated animals clustered apart from the controls. Gene set enrichment analysis revealed that fetal hypothalamic genes stimulated by maternal and fetal TCS infusion were significantly enriching for cell cycle, reproductive process, and feeding behavior, whereas the inhibited genes were significantly enriching for chromatin modification and metabolism of steroids, lipoproteins, fatty acids, and glucose (P &lt; .05). In conclusion, short-term infusion of TCS induces vigorous changes in the fetal hypothalamic transcriptomics, which are mainly related to food intake pathways and metabolism. If these changes persist to postnatal life, they could result in adverse consequences in adulthood.

Effect of fetal thyroidectomy on brown adipose tissue and thermoregulation in newborn lambs

1996 ◽  
Vol 8 (6) ◽  
pp. 995 ◽  
Author(s):  
SJ Schermer ◽  
JA Bird ◽  
MA Lomax ◽  
DA Shepherd ◽  
ME Symonds
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Late Gestation ◽  
Guanosine Diphosphate ◽  
Functional Development ◽  
Brown Adipose ◽  
Colonic Temperature ◽  
Shivering Thermogenesis

The effect of fetal thyroidectomy on thermoregulation in newborn lambs was investigated. Seven of 14 lambs born normally at term were thyroidectomized at Day 127 of gestation. Colonic temperature and oxygen consumption were measured during non-rapid eye movement sleep 6-45 h after birth. All lambs were then killed and perirenal brown adipose tissue was sampled for measurement of thermogenic activity (guanosine diphosphate binding), uncoupling protein and lipid contents. Thyroidectomized lambs tended to have a mean colonic temperature 2.35 degrees C lower (P = 0.067) than controls and two became hypothermic (i.e. colonic temperature < 35 degrees C). Thyroidectomized lambs exhibited lower rates of oxygen consumption (P = 0.05) and an increased incidence of shivering thermogenesis. The perirenal adipose tissue of these lambs had a lower thermogenic activity (P < 0.01), less uncoupling protein (P < 0.01) and higher lipid content (P = 0.072) compared with intact controls. It is concluded that fetal thyroidectomy results in a decreased ability of newborn lambs to utilize nonshivering thermogenesis in brown adipose tissue as well as increasing the incidence of hypothermia. These changes are associated with decreased synthesis of uncoupling protein and functional development of brown adipose tissue in the late gestation fetus.

Placental restriction of fetal growth decreases IGF1 and leptin mRNA expression in the perirenal adipose tissue of late gestation fetal sheep

2008 ◽  
Vol 294 (5) ◽  
pp. R1413-R1419 ◽  
Author(s):  
Jaime A. Duffield ◽  
Tony Vuocolo ◽  
Ross Tellam ◽  
Bernard S. Yuen ◽  
Beverly S. Muhlhausler ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mrna Expression ◽  
Fetal Growth ◽  
Visceral Adipose Tissue ◽  
Late Gestation ◽  
Postnatal Life ◽  
Fetal Sheep ◽  
Pat Gene ◽  
Visceral Adipose ◽  
And Control

Placental restriction (PR) of fetal growth results in a low birth weight and an increased visceral fat mass in postnatal life. We investigated whether PR alters expression of genes that regulate adipogenesis [IGF1, IGF1 receptor (IGF1R), IGF2, IGF2R, proliferator-activated receptor-γ, retinoid-X-receptor-α], adipocyte metabolism (lipoprotein lipase, G3PDH, GAPDH) and adipokine signaling (leptin, adiponectin) in visceral adipose tissue before birth. PR was induced by removal of the majority of endometrial caruncles in nonpregnant ewes before mating. Fetal blood samples were collected from 116 days gestation, and perirenal visceral adipose tissue (PAT) was collected from PR and control fetuses at 145 days. PAT gene expression was measured by quantitative RT-PCR. PR fetuses had a lower weight (PR 2.90 ± 0.32 kg; control, 5.12 ± 0.24 kg; P < 0.0001), mean gestational arterial Po2 ( P < 0.0001), plasma glucose ( P < 0.01), and insulin concentrations ( P < 0.02), than controls. The expression of IGF1 mRNA in PAT was lower in the PR fetuses (PR, 0.332 ± 0.063; control, 0.741 ± 0.083; P < 0.01). Leptin mRNA expression in PAT was also lower in PR fetuses (PR, 0.077 ± 0.009; control, 0.115 ± 0.013; P < 0.05), although there was no difference in the expression of other adipokine or adipogenic genes in PAT between PR and control fetuses. Thus, restriction of placental and hence, fetal substrate supply results in decreased IGF1 and leptin expression in fetal visceral adipose tissue, which may alter the functional development of the perirenal fat depot and contribute to altered leptin signaling in the growth-restricted newborn and the subsequent emergence of an increased visceral adiposity.

Cardiovascular and hypothalamic-pituitary-adrenal axis development in late gestation fetal sheep and young lambs following modest maternal nutrient restriction in early gestation

2000 ◽  
Vol 12 (8) ◽  
pp. 443 ◽  
Author(s):  
P. Hawkins ◽  
C. Steyn ◽  
H. H. G. McGarrigle ◽  
N. A. Calder ◽  
T. Saito ◽  
...  
Keyword(s):  
Vascular Resistance ◽  
Hpa Axis ◽  
Femoral Artery ◽  
Cardiovascular Response ◽  
Late Gestation ◽  
Postnatal Life ◽  
Fetal Life ◽  
Fetal Sheep ◽  
Hypothalamic Pituitary Adrenal ◽  
Maternal Undernutrition

The effect of a 15% reduction in maternal nutrition for the first 70 days of gestation on cardiovascular and hypothalamic–pituitary–adrenal (HPA) axis responses to administration of corticotropin releasing hormone (CRH) + arginine vasopressin (AVP) was studied at 128 0.7 days gestation in fetal sheep and postnatally, at 85 4.5 days in young lambs. The effect on the fetal cardiovascular response to acute hypoxaemia was also examined. Under basal conditions, fetal heart rate (FHR) was reduced (P<0.05) and basal femoral artery vascular resistance (FVR) was increased (P<0.05) in fetuses of dietary-restricted (R) ewes compared with controls (C). Fetal mean arterial pressure (MAP) was similar in both groups. Femoral artery vascular resistance was also greater during hypoxaemia in R fetuses compared with C fetuses (P<0.05), suggesting that chemoreflex mechanisms were augmented in the R group. The fetal ACTH response to CRH + AVP was similar in both groups. However, cortisol responses to CRH + AVP were smaller in R fetuses compared with C fetuses (P<0.05). Postnatally, basal MAP (P<0.05), and ACTH (P<0.01) and cortisol (P<0.001) responses were greater in R lambs compared with C lambs. It was concluded that modest maternal undernutrition during pregnancy alters development of the cardiovascular system, producing elevated blood pressure in postnatal life. Development of the HPA axis is also altered, with reduced activity during fetal life, but increased activity postnatally. The data suggest that the HPA axis may play a role in mediating the elevation of MAP in R lambs.

Lower citrate synthase activity, mitochondrial complex expression, and fewer oxidative myofibers characterize skeletal muscle from growth restricted fetal sheep

2021 ◽  
Author(s):  
Jane Stremming ◽  
Eileen Chang ◽  
Leslie A Knaub ◽  
Michael L Armstrong ◽  
Peter R Baker ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Oxidative Metabolism ◽  
Mitochondrial Respiration ◽  
Citrate Synthase ◽  
Fiber Type ◽  
Late Gestation ◽  
Postnatal Life ◽  
Type I ◽  
Mitochondrial Complex ◽  
Fetal Sheep

Skeletal muscle from the late gestation sheep fetus with intrauterine growth restriction (IUGR) has evidence of reduced oxidative metabolism. Using a sheep model of placental insufficiency and IUGR, we tested the hypothesis that by late gestation, IUGR fetal skeletal muscle has reduced capacity for oxidative phosphorylation due to intrinsic deficits in mitochondrial respiration. We measured mitochondrial respiration in permeabilized muscle fibers from biceps femoris (BF) and soleus (SOL) from control and IUGR fetal sheep. Using muscles including BF, SOL, tibialis anterior (TA), and flexor digitorum superficialis (FDS), we measured citrate synthase (CS) activity, mitochondrial complex subunit abundance, fiber type distribution, and gene expression of regulators of mitochondrial biosynthesis. Ex vivo mitochondrial respiration was similar in control and IUGR muscle. However, CS activity was lower in IUGR BF and TA, indicating lower mitochondrial content, and protein expression of individual mitochondrial complex subunits was lower in IUGR TA and BF in a muscle specific pattern. IUGR TA, BF, and FDS also had lower expression of type I oxidative fibers. Fiber type shifts that support glycolytic instead of oxidative metabolism may be advantageous for the IUGR fetus in a hypoxic and nutrient deficient environment, whereas these adaptions may be maladaptive in postnatal life.

scholarly journals Prolactin, the prolactin receptor and uncoupling protein abundance and function in adipose tissue during development in young sheep

2005 ◽  
Vol 184 (2) ◽  
pp. 351-359 ◽  
Author(s):  
S Pearce ◽  
H Budge ◽  
A Mostyn ◽  
E Genever ◽  
R Webb ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Prolactin Receptor ◽  
Plasma Concentrations ◽  
Primary Role ◽  
Brown Adipose ◽  
Close Relationship ◽  
Acute Increase ◽  
Colonic Temperature ◽  
And Function

A primary role of the prolactin receptor (PRLR) during fetal and postnatal development has been suggested to be the regulation of uncoupling protein (UCP) expression. We, therefore, determined whether: (1) the rate of loss of UCP1 from brown adipose tissue after birth was paralleled by the disappearance of PRLR; and (2) administration of either pituitary extract prolactin (PRL) containing a mixture of posttranslationally modified forms or its pseudophosphorylated form (S179D PRL) improved thermoregulation and UCP1 function over the first week of neonatal life. PRLR abundance was greatest in adipose tissue 6 h after birth before declining up to 30 days of age, a trend mirrored by first a gain and then a loss of UCP1. In contrast, in the liver – which does not possess UCPs –a postnatal decline in PRLR was not observed. Administration of PRL resulted in an acute increase in colonic temperature in conjunction with increased plasma concentrations of non-esterified fatty acids and, as a result, the normal postnatal decline in body temperature was delayed. S179D PRL at lower concentrations resulted in a transient rise in colonic temperature at both 2 and 6 days of age. In conclusion, we have demonstrated a close relationship between the ontogeny of UCP1 and the PRLR. Exogenous PRL administration elicits a thermogenic effect suggesting an important role for the PRLR in regulating UCP1 function.

The effect of hypothalamo-pituitary disconnection on the renin-angiotensin system in the late-gestation fetal sheep

2005 ◽  
Vol 288 (5) ◽  
pp. R1279-R1287 ◽  
Author(s):  
Kai Chen ◽  
Luke C. Carey ◽  
Jingfang Liu ◽  
Nancy K. Valego ◽  
Stephen B. Tatter ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Fetal Tissue ◽  
Late Gestation ◽  
Receptor Subtype ◽  
Postnatal Life ◽  
Ang Ii ◽  
Fetal Sheep ◽  
Angiotensin System ◽  
Renin Angiotensin

The activity of the renin-angiotensin system (RAS) increases significantly in the late-gestation fetal sheep. Fetal cortisol is also increased during this time, and it is thought that the increase in cortisol may modulate the RAS changes. Previous studies have examined the effects of cortisol infusion on RAS activity, but the effects of blocking the peripartum increase in cortisol concentrations on the developmental changes in the RAS are not known. Therefore, we utilized the technique of hypothalamic-pituitary disconnection (HPD), which prevents the cortisol surge from occurring, to investigate the importance of the late-gestation increase in cortisol on the ontogenic changes in RAS activity. HPD of fetal sheep was performed at 120 days of gestational age (dGA), and fetuses were delivered between 135 and 139 dGA. Control fetuses were sham operated. HPD blocked the late-gestation cortisol increase but did not alter renal renin mRNA, renal renin or prorenin protein content, nor plasma renin levels compared with sham operated. However, HPD fetuses had increased ANG II receptor subtype 1 (AT1) mRNA and protein expression in the kidney and lungs. ANG II receptor subtype 2 (AT2) expression was not altered in these tissues at either mRNA or protein level. HPD did not change AT1 or AT2 mRNA in the left ventricle but did result in decreased protein levels for both receptors. These studies demonstrate that blockade of the naturally occurring increase in fetal cortisol concentration in late gestation is associated with tissue-specific alterations in expression of AT1 and AT2 receptors. These changes may impact on fetal tissue maturation and hence have consequences in postnatal life.

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