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Biomedical subjects

A L Fowden

Publications and source records attributed to A L Fowden.

At least 73 records · Page 4Linked to original sources
PubMed1999

Activation of the adult mode of ovine growth hormone receptor gene expression by cortisol during late fetal development.

The developmental and tissue-specific regulation of growth hormone receptor (GHR) mRNA expression is complex and involves alternate leader exon usage. The transcript composition of hepatic GHR mRNA has therefore been determined in fetal sheep during late gestation and after experimental manipulation of fetal plasma cortisol levels by fetal adrenalectomy and exogenous cortisol infusion, using RNase protection assays and a riboprobe containing exons 1A, 2, and 3 of the ovine GHR gene. Expression of the adult liver-specific GHR mRNA transcript containing exon 1A was not detected earlier than 138 days of gestation (term 145 +/-2 days). Thereafter, expression of this leader exon increased and accounted for 25-30% of the total GHR mRNA in the fetal liver at term. Hepatic GHR mRNA derived from leader exons other than 1A was detectable at 97 days and increased in abundance toward term in parallel with the normal prepartum rise in fetal plasma cortisol. Abolition of this cortisol surge by fetal adrenalectomy prevented both the activation of exon 1A expression and the prepartum rise in GHR mRNA derived from the other leader exons in fetal ovine liver. Conversely, raising cortisol levels by exogenous infusion earlier in gestation prematurely activated exon 1A expression and enhanced the abundance of GHR mRNA transcripts derived from the other leader exons. Cortisol therefore appears to activate the adult mode of GHR gene expression in fetal ovine liver during late gestation. These observations have important implications for the maturation of the somatotrophic axis and for the onset of GH-dependent growth after birth.

Adrenalectomy↗
PubMed1999

Intestinal macromolecule absorption in the fetal pig after infusion of colostrum in utero.

The ability of the fetal pig intestine to absorb large proteins was investigated in utero. Six pregnant sows were anesthetized (Na pentobarbital) at 99-102 d of gestation (term = 115 +/- 2 d), and a catheter was inserted into the esophagus of two to three fetuses per sow. Via these catheters, sterile solutions (10.0 mL) of colostrum whey (CW, n = 5), milk whey (MW, n = 5), or amniotic fluid (AF, n = 4) were infused into the fetal pig stomachs every 6 h for 6-8 d starting on the day after surgery (d 0). Levels of IgG in the three fluids were 120, 0.5, and 0 mg/mL, respectively. During the first 2-3 d of infusion, plasma IgG levels rose rapidly in the CW fetuses (to 7.5 +/- 0.8 mg/mL), whereas IgG remained absent in plasma from MW and AF fetuses. Absorption of a macromolecule marker, BSA, was also higher when the marker was given with CW rather than with MW or AF. However, when all three treatment groups were given CW + BSA on the last experimental day (d 6-8), the mean BSA increment in the CW group was only 5-8% of that in the AF group, with intermediate values for the MW group. Neither at the beginning nor at the end of the experiment was macromolecule uptake in individual CW fetuses correlated with their cortisol level in plasma. The prenatal pig intestine is similar to the neonatal pig intestine in that colostrum stimulates both the macromolecule absorption and the cessation of macromolecule uptake (intestinal closure). However, fetal pigs have a lower protein absorptive capacity and a longer preclosure period than newborn pigs; this may be related to an immature structure and function and a slow enterocyte proliferation rate in the prenatal pig intestine.

Amniotic Fluid↗
PubMed1999

Pancreatic alpha cell function in the fetal foal during late gestation.

Plasma glucagon concentrations were measured in chronically catheterized fetal ponies and their mothers between 260 days of gestation and term (approximately 335 days). Fetal alpha cell responses to arginine and variations in fetal glycaemia were also examined during late gestation. Immunoreactive glucagon was present in fetal plasma at 260 days of gestation and its concentration in utero increased after 320 days and then again at birth. Maternal plasma glucagon concentrations were higher after 300 days than earlier in gestation but were lower than the corresponding fetal value throughout the period of gestation studied. Fetal alpha cells responded rapidly to intravenous arginine infusion but not to changes in the fetal glucose level induced by maternal fasting for 36 h or by intrafetal infusion of glucose. The maximal increment in fetal plasma glucagon in response to arginine occurred at the end of the 5 min infusion and was positively correlated to the basal pre-infusion plasma glucagon concentrations. Fetal plasma glucagon concentrations were unaffected by either hyper- or hypoglycaemia. In contrast, maternal plasma glucagon levels were significantly increased by fasting. These observations indicate that equine pancreatic alpha cells are functional in utero but that they are unresponsive to variations in glycaemia until after birth.

Amino Acids↗
PubMed1998

Developmental regulation of glucogenesis in the sheep fetus during late gestation.

1. Using tracer methodology, endogenous glucose production was measured in twenty-six chronically catheterized sheep fetuses during normal fed conditions and in response to a 48 h period of maternal fasting at different gestational ages during the last 10-15 days of gestation (term, 145 +/- 2 days). 2. In normal fed conditions, the rate of fetal glucose production was negligible until 143-145 days when it rose significantly to account for 50 % of the glucose used by the fetus. The rise in fetal glucogenesis towards term closely parallelled the normal prepartum rise in fetal plasma cortisol and catecholamines. 3. Maternal fasting for 48 h induced endogenous glucose production in fetuses at 139-141 days but not at 133-135 days of gestation. Maternal fasting also induced increases in the plasma cortisol and noradrenaline levels in all the fetuses studied. Fetal plasma cortisol levels at the end of the fast and the increment in fetal plasma cortisol during maternal fasting were significantly greater in the older groups of fasted animals. 4. When the data from all the fetuses were combined, partial correlation analysis of fetal glucose production and the log plasma concentrations of cortisol and total catecholamines showed that plasma cortisol was the predominant regulator of fetal glucogenesis during late gestation. However, once plasma cortisol levels exceeded 17.5 ng ml-1, plasma catecholamines were a major influence on fetal glucogenesis. 5. The results show that glucogenesis occurs in fetal sheep during late gestation in conditions in which the fetal plasma concentrations of cortisol and catecholamines are elevated. They also suggest that cortisol enhances the capacity for glucogenesis in utero, while catecholamines actually activate glucose production in sheep fetuses close to term.

Animals↗
PubMed1998

Transcriptional regulation of insulin-like growth factor-II gene expression by cortisol in fetal sheep during late gestation.

The objective of this study was to determine the mechanisms by which cortisol down-regulates hepatic insulin-like growth factor-II (IGF-II) gene expression in late gestation. Leader exons 6 and 7 of the ovine IGF-II gene, with their 5'-flanking regions, were first isolated. Characterization of transcription start sites revealed a unique site for exon 6 and three dispersed sites for exon 7. Nuclear run-on assays showed a 5-fold higher transcription rate of the IGF-II gene in liver of adrenalectomized fetuses compared with control animals, suggesting that regulation of IGF-II gene expression by cortisol is at the transcriptional level. RNase protection assays demonstrated hepatic leader exon 7 expression in adrenalectomized fetuses to be more than 2-fold higher than in controls, whereas it was reduced by 50% in cortisol-infused fetuses compared with controls. There was no effect on the expression of other leader exons. Functions of the upstream regulatory region of leader exon 7 (i.e. promoter P4) were investigated by luciferase transient expression. A region of -172 bases downstream relative to the first transcription site of leader exon 7 was shown to retain basal promoter activity and respond to cortisol. These results suggest that cortisol may induce the prenatal decline in ovine hepatic IGF-II expression by suppressing promoter P4 of the IGF-II gene.

Animals↗
PubMed1998

The effects of intrafetal ACTH administration on the outcome of pregnancy in the mare.

Enhanced adrenocortical activity in the fetus is related to the onset of parturition in many species. The aim of this study was to determine the effect of injection of fetal ACTH on gestational length and fetal viability in the horse. Pony mares (n=23) were studied from 300 days gestation. Seven control mares (Group 1) received three consecutive intrafetal injections of sterile water, while fetuses of a further 16 mares received Depot ACTH1-24. These mares were either allowed to foal spontaneously (Group 2, n=4) or delivery was induced within 3 days of the last fetal injection (Group 3, n=7); 5 mares aborted within 48 h of intrafetal ACTH injection. Maternal plasma progestagen concentrations increased significantly (P<0.05) in Groups 2 and 3 mares following intrafetal ACTH injection, compared with Group 1 mares. All Group 1 mares delivered live foals at a median gestational age of 327 days (interquartile range, 323 334), except one that aborted 16 days after the last fetal injection. Gestational length was significantly (P<0.05) shortened in Group 2 mares (median 314 [312-314]) days compared with controls. Group 1 and Group 2 foals showed normal postnatal adaptive responses and endocrine (plasma cortisol/progestagens) patterns. Group 3 mares delivered live foals at 306 (306-308) days gestation except one that aborted. Their foals were less mature compared with Groups 1 and 2 foals. Eight ACTH-injected fetuses were meconium-stained at delivery, including four that were aborted. Eight mares had thickened placentae, including three that aborted. The data show that both precocious maturation of the equine fetus and a significant reduction in gestational length compared with controls may be achieved in pony mares by intrafetal ACTH injections. This is probably mediated via adrenal regulation of fetal maturation and production of maternal progestagens.

Adrenocorticotropic Hormone↗
PubMed1998

Developmental changes in plasma angiotensin-converting enzyme concentration in fetal and neonatal lambs.

Relationships between plasma angiotensin-converting enzyme (ACE) and cortisol, and blood pressure were examined in chronically catheterized ewes and their fetuses during late gestation (111-141 days, term 145 +/- 2 days). Plasma ACE was also measured in non-pregnant adult ewes and in lambs over the first 5 weeks of life. In fetuses near term (136-141 days), plasma ACE was greater than in those studied earlier in gestation; overall, plasma ACE correlated with gestational age (r = 0.72). The ontogenic rise in plasma ACE was associated with prepartum increases in plasma cortisol (r = 0.67) and blood pressure (r = 0.66). No relationship was observed between plasma ACE and partial pressure of oxygen in utero. Peak plasma ACE concentration observed in fetuses near term was maintained in newborn lambs for 3 days after birth. By 2 weeks of postnatal age, plasma ACE had decreased to the value seen in non-pregnant adult ewes. Maternal plasma ACE was similar at all gestational ages studied, and was lower than that observed in non-pregnant ewes. Therefore, in the sheep fetus, plasma ACE increased towards term in association with the prepartum cortisol surge. Developmental changes in ACE activity may be partly responsible for the ontogenic rise in fetal blood pressure.

Age Factors↗
PubMed1998

Control of hepatic insulin-like growth factor II gene expression by thyroid hormones in fetal sheep near term.

The effects of thyroid hormones on hepatic insulin-like growth factor (IGF) II gene expression and their interaction with cortisol in the ontogenic control of this gene were investigated in fetal sheep during late gestation (term 145 +/- 2 days) and after experimental manipulation of fetal plasma hormone concentrations. In intact fetuses, a significant decrease in hepatic IGF-II mRNA abundance was observed between 127-130 and 142-145 days of gestation, which coincided with the normal prepartum rise in plasma cortisol and triiodothyronine (T3) concentrations. This ontogenic decline in hepatic IGF-II gene expression was abolished in fetuses in which the prepartum rise in plasma T3, but not cortisol, was prevented by fetal thyroidectomy. At 127-130 days, downregulation of hepatic IGF-II mRNA abundance was induced prematurely in intact fetuses by an infusion of cortisol for 5 days (2-3 mg . kg-1 . day-1 iv). Plasma concentrations of cortisol and T3 in the cortisol-infused intact fetuses were increased to values seen close to term. Similar findings were observed in thyroidectomized fetuses, in which, despite thyroidectomy, cortisol infusion significantly increased plasma T3 concentrations and caused a premature decrease in hepatic IGF-II mRNA levels. However, in intact fetuses at 127-130 days, the increasing of T3 concentrations alone by exogenous T3 infusion (8-12 microg . kg-1 . day-1 iv for 5 days) had no effect on hepatic IGF-II mRNA levels. Overall, a decrease in hepatic IGF-II mRNA abundance was only observed in fetuses in which there were concurrent increases in plasma cortisol and T3 concentrations. When observations from all fetuses were considered, irrespective of gestational age or treatment, hepatic IGF-II mRNA levels were negatively correlated with plasma cortisol and T3 but not thyroxine concentrations. Partial correlation analysis of hepatic IGF-II, cortisol, and T3 values showed that the plasma concentration of cortisol in the fetus had the predominant effect on hepatic IGF-II mRNA abundance. These findings show that T3 may mediate, in part, the maturational effects of cortisol on hepatic IGF-II gene expression but that it is ineffective without a concomitant rise in fetal plasma cortisol. Hence, increased concentrations of both cortisol and T3 appear necessary to induce downregulation of hepatic IGF-II mRNA abundance in fetal sheep close to term.

Animals↗
PubMed1997

Glucose, lactate and oxygen metabolism in the fetal pig during late gestation.

Using [U-14C]glucose tracer, rates of umbilical uptake, utilization and production of glucose, and of CO2 production from glucose carbon, were measured in seven chronically catheterized fetal pigs, when the sow was in the fed state, between 100 and 113 days of gestation (term, 114 +/- 2 days). At the same time, rates of umbilical O2 and lactate uptake were determined in all seven fetuses by the Fick principle. The mean fetal rates of umbilical glucose uptake, glucose utilization and CO2 production from glucose carbon were 38.4 +/- 4.2, 41.3 +/- 5.2 and 126.9 +/- 12.6 mumol min-1 (kg fetal body weight)-1, respectively (n = 7), No glucose production was therefore detected in the fetuses. Production of CO2 from glucose carbon accounted for 37.3 +/- 3.4% (n = 7) of the umbilical O2 uptake, which averaged 340 +/- 13 mumol min-1 kg-1 (n = 7). There was also significant umbilical lactate uptake in the fetal piglets when the sow was in the fed state (32.6 +/- 10.4 mumol min-1 kg-1, n = 7, P < 0.05). No significant changes in fetal glucose, O2 or lactate metabolism were observed with increasing age towards term. The fetal rates of glucose metabolism and of umbilical uptake of O2 and lactate were not correlated with fetal blood glucose level. Hence, glucose is used for both oxidative and non-oxidative metabolism in utero and is an important, although not the sole, source of carbon for metabolic processes in the fetal pig during late gestation.

Animals↗
PubMed1997

Changes in the maternal and fetal renin-angiotensin systems in response to angiotensin II type 1 receptor blockade and angiotensin-converting enzyme inhibition in pregnant sheep during late gestation.

The effects of maternal administration of either an angiotensin II type 1 (AT1) receptor antagonist (GR138950) or an angiotensin-converting enzyme (ACE) inhibitor (captopril) on the renin-angiotensin system (RAS) were investigated in chronically catheterized ewes and their fetuses during late gestation. From 127 +/- 1 days of gestation until parturition at 145 +/- 2 days, each ewe received daily i.v. injections of GR138950 (3 mg kg-1, n = 10 animals) or captopril (3 mg kg-1, n = 6) or an equivalent volume of vehicle solution (0.9% NaCl, n = 10). On the first day of treatment, plasma renin concentrations in the pregnant ewe increased within 2 h of administration of either GR138950 (median change followed by lower and upper quartiles (25%, 75%): +38.3 ng ml-1 h-1 (15.6, 80.7); P < 0.05) or captopril (+22.1 ng ml-1 h-1 (19.2, 28.8); P < 0.05). Maternal plasma concentrations of angiotensin II (AII) also increased by 871 pg ml-1 (555, 1340; P < 0.05) in the GR138950-treated ewes. In the fetuses of both groups of drug-treated animals, an increase in plasma renin concentration was observed within 2 h of maternal treatment with either GR138950 (+11.6 ng ml-1 h-1 (1.2, 18.6); P < 0.05) or captopril (+59.3 ng ml-1 h-1 (41.7, 74.6); P < 0.05). These short-term changes in circulating renin and AII concentrations observed in the pregnant ewe were sustained after 1 week of GR138950 administration. In addition, 1 week of GR138950 treatment decreased plasma angiotensinogen (Ao) concentrations in both the ewe (-0.36 microgram ml-1 (-0.58, -0.16); P < 0.05) and the fetus (-0.43 microgram ml-1 (-0.59, -0.09); P < 0.05). A long-term reduction in maternal plasma AII, and an increase in fetal plasma renin concentration, were associated with 1 week of captopril administration. Neither drug had any consistent effect on plasma ACTH or cortisol concentrations in the pregnant ewe or fetus. These findings show that, during ovine pregnancy, antagonism of maternal AII activity, either by blockade of the AT1 receptor or by inhibition of AII synthesis, induces changes in the circulating components of the RAS in the mother and fetus. In both the pregnant ewe and fetus, the RAS is shown to be activated by suppression of AII activity.

Angiotensin II↗
PubMed1996

Comparison of angiotensin II type 1 receptor blockade and angiotensin-converting enzyme inhibition in pregnant sheep during late gestation.

1. The effects of antagonism of the maternal renin-angiotensin system (RAS) with either an angiotensin II type 1-(AT1) specific receptor blocker (GR138950) or an angiotensin-converting enzyme (ACE) inhibitor (captopril) were compared in chronically-catheterised ewes and their foetuses during late gestation. 2. Daily from 127 +/- 1 days of gestation until parturition at 145 +/- 2 days, each ewe received i.v. either GR138950 (3 mg kg-1; n = 10), captopril (3 mg kg-1; n = 6) or an equivalent volume of vehicle solution (0.9% w/v saline; n = 10). 3. Within 2 h of drug administration, GR138950 abolished the maternal, but not the foetal, pressor responses to angiotensin II (AII; 100-188 ng kg-1, i.v.; P < 0.05), whereas captopril abolished both the maternal and foetal pressor responses to angiotensin I (AI; 400-750 ng kg-1, i.v.; P < 0.05). 4. On the first day of treatment, maternal blood pressure decreased in all GR138950-treated (-21 +/- 4 mmHg; P < 0.05) and captopril-treated (-13 +/- 5 mmHg; P > 0.05) ewes at 2 h after drug administration. Captopril also significantly decreased foetal blood pressure by 5 +/- 1 mmHg (P < 0.05). However, foetal blood pressure in the GR138950-treated animals remained unchanged. Maternal and foetal heart rates were unaffected by any treatment. Uterine blood flow was significantly reduced within 2 h of both GR138950 (-130 +/- 20 ml min-1; P < 0.05) and captopril (-72 +/- 16 ml min-1; P < 0.05) administration. 5. On the first day of treatment, maternal arterial haemoglobin (Hb) concentration and oxygen (O2) content increased at 2 h in all GR138950-treated and captopril-treated ewes. Foetal arterial pH and oxygenation (O2 content, O2 saturation and Pao2) were reduced by a similar extent in both groups of drug-treated ewes. 6. After one week of daily GR138950 administration, maternal blood pressure decreased from a pretreatment value of 96 +/- 5 mmHg on day 1 to 79 +/- 2 mmHg by day 7 (P < 0.05). Captopril treatment had no long-term effect on maternal blood pressure. Although foetal blood pressure increased by 3 +/- 1 mmHg over a week of vehicle treatment (P < 0.05), no significant differences were observed between the long-term changes in foetal blood pressure in all three groups of animals. 7. There were no long-term effects of drug administration on maternal Hb concentration or oxygenation, or on the foetal haematological parameters. However, changes in maternal PaCo2 observed in the GR138950-treated (+1.4 +/- 0.5 mmHg; P < 0.05) and captopril-treated (+3.3 +/- 1.1 mmHg; P > 0.05) ewes were significantly different from those seen in the vehicle-treated animals (P < 0.05). 8. There were no apparent adverse effects of maternal GR138950 or captopril treatment on foetal viability. 9. The present study demonstrated that administration of either GR138950 or captopril to pregnant ewes effectively blocked the maternal RAS, and caused hypotension and a decrease in uterine blood flow. However, only captopril appeared to cross the placenta to influence directly the RAS of the sheep foetus. This suggests that the fall in foetal oxygenation observed after AT1-specific receptor blockade and ACE inhibition originates primarily from changes in the maternal and/or placental vasculature. Despite these changes, neither GR138950 nor captopril were detrimental to the outcome of pregnancy when foetal blood loss was kept to a minimum.

Angiotensin Receptor Antagonists↗
PubMed1996

The ontogeny of hepatic growth hormone receptor and insulin-like growth factor I gene expression in the sheep fetus during late gestation: developmental regulation by cortisol.

The effects of cortisol on hepatic GH receptor and insulin-like growth factor-I (IGF-I) gene expression were investigated in sheep fetuses during late gestation and after experimental manipulation of plasma cortisol levels by fetal adrenalectomy and exogenous infusion of cortisol. Hepatic GH receptor and IGF-I messenger RNA (mRNA) levels increased with increasing gestational age in parallel with the normal rise in fetal cortisol levels toward term (145 +/- 2 days). These increases in mRNA abundance toward term were prevented when the prepartum cortisol surge was abolished by fetal adrenalectomy and were stimulated prematurely in fetuses younger than 130 days by exogenous infusion of cortisol. Both the class 1 and class 2 transcripts of the IGF-I gene were increased when cortisol levels were elevated either endogenously or exogenously. However, there were no significant changes in fetal plasma IGF-I levels either with increasing gestational age or in response to experimental manipulation of the fetal cortisol level. When the data from all the fetuses were combined irrespective of treatment or gestational age, there were significant positive correlations between the log plasma cortisol concentration in utero and the abundance of GH receptor and IGF-I mRNA in the fetal liver. There was also a significant inverse relationship between log plasma cortisol and the ratio of class 1 to class 2 transcript abundance in the fetal liver. These findings show that cortisol is a physiological regulator of hepatic GH receptor and IGF-I gene expression in fetal sheep during late gestation and indicate that it preferentially increases the class 2 transcript of the IGF-I gene. The prepartum cortisol surge therefore appears to have an important maturational role in initiating the perinatal switch from the fetal to adult modes of somatotrophic regulation.

Adrenalectomy↗
PubMed1996

The effects of cortisol on the growth rate of the sheep fetus during late gestation.

Using indwelling crown-rump length (CRL)-measuring devices, the growth rate of sheep fetuses was monitored during late gestation and after experimental manipulation of fetal plasma cortisol by exogenous infusion and fetal adrenalectomy. In intact control fetuses, the increment in CRL declined progressively during the last 20-25 days of gestation: mean +/- S.E.M. values fell from 5.5 +/- 0.4 mm/day (n = 12) at 21-25 days before delivery to 2.5 +/- 0.3 mm/day (n = 12) in the last 5 days before birth (P < 0.01). These changes closely parallelled the normal prepartum increase in fetal plasma cortisol which rose from 19.3 +/- 3.3 nmol/l (n = 10) at 21-25 days before birth to 177.4 +/- 19.0 nmol/l (n = 10) in the final 5 days before delivery (P < 0.01). When this cortisol surge was prevented by fetal adrenalectomy, there was no decrease in CRL increment towards normal term: mean CRL increment in the 5 days before normal term (4.8 +/- 0.6 mm/day, n = 5) was similar to that observed at 21-25 days before term (4.7 +/- 0.4 mm/day, n = 5). At delivery at term, the body weight (4.116 +/- 0.280 kg, n = 5) and CRL (51.9 +/- 1.7 cm, n = 5) of the adrenalectomized fetuses were significantly greater than the corresponding values in their sham-operated controls (2.877 +/- 0.070 kg and 47.1 +/- 1.6 cm, n = 6, respectively). In contrast with the sham-operated controls, plasma glucose and insulin levels in the adrenalectomized fetuses decreased towards term. Infusion of cortisol into the preterm fetus for 5 days increased fetal plasma cortisol to term levels and decreased the CRL increment to a value (1.8 +/- 0.5 mm/day, n = 8) which was similar to that observed in untreated controls during the last 5 days before spontaneous delivery at term (2.1 +/- 0.3 mm/day, n = 6). There were no significant alterations in the fetal arterial concentrations of plasma glucose or insulin in response to fetal cortisol infusion. When all the data were combined irrespective of treatment or proximity to delivery, the fetal plasma concentrations of cortisol (P < 0.001) and glucose (P < 0.04), but not insulin (P > 0.05), had a significant effect on the fetal CRL increment measured over 5-day periods during the last 25-30 days of gestation. These findings show that cortisol inhibits growth of the axial skeleton in the sheep fetus during late gestation. They also indicate that the prepartum cortisol surge may be responsible for the normal decline in fetal growth rate observed towards term in this species.

Adrenalectomy↗
PubMed1995

The effects of thyroid hormones on oxygen and glucose metabolism in the sheep fetus during late gestation.

1. The effects of thyroid hormones on fetal metabolism during late gestation were examined by measuring the rates of glucose and oxygen utilization rates in chronically catheterized sheep fetuses made hypothyroid by either fetal thyroidectomy (TX) or hypophysectomy (HX). The values were compared with those in intact fetuses and in thyroxine (T4)-treated TX and HX fetuses. 2. Umbilical O2 uptake expressed on a weight-specific basis was reduced by 20-30% in the hypothyroid fetuses and was restored to normal values when plasma T4 levels were maintained in the TX and HX fetuses by exogenous T4 administration. 3. The low O2 consumption rates of the untreated hypothyroid fetuses were accompanied by fetal growth retardation, an abnormal blood gas status, and in the TX fetuses, by significant reductions in the rates of glucose oxidation, CO2 production from glucose carbon and O2 utilization for glucose oxidation. 4. When T4 levels were maintained in the TX fetuses, these metabolic rates and fetal blood gas status were restored to their normal values. Replacement of T4 also sustained growth in TX but not in HX fetuses. 5. When the data from all fetuses were combined irrespective of treatment, there were significant positive correlations between plasma levels of T4 (but not triiodothyronine (T3)) and the rates of umbilical O2 uptake, glucose oxidation, CO2 production from glucose carbon and O2 utilization for glucose oxidation in the individual fetuses. 6. These findings demonstrate that T4 is a physiological regulator of O2 utilization by the sheep fetus close to term.

Animals↗
PubMed1995

Endocrine regulation of fetal growth.

Hormones have an important role in the control of fetal growth. They act on both tissue accretion and differentiation and enable a precise and orderly pattern of growth to occur during late gestation. In part, their actions on growth may be mediated by other growth factors such as the insulin-like growth factors (IGFs). Insulin stimulates fetal growth by increasing the mitotic drive and nutrient availability for tissue accretion. It has little effect on tissue differentiation. In contrast, the main effects of cortisol in utero are on tissue differentiation and maturation. Cortisol appears to act directly on the cells to alter gene transcription or post-translational processing of the gene products. Cortisol may also initiate the transition from the fetal to the adult modes of growth regulation by inducing the switch from IGF-II to IGF-I gene expression in the fetal liver. Thyroxine affects both tissue accretion and differentiation in the fetus by a combination of metabolic and non-metabolic mechanisms. Pituitary growth hormone, on the other hand, appears to have little part in the control of fetal growth, unlike its role postnatally. Fetal hormones, therefore, promote growth and development in utero by altering both the metabolism and gene expression of the fetal tissues. These hormonal actions ensure that fetal growth rate is commensurate with the nutrient supply and that prepartum maturation occurs in preparation for extrauterine life.

Animals↗