Biomedical subjects

S M Woodall

Publications and source records attributed to S M Woodall.

7 recordsLinked to original sources

PubMed1999

Administration of growth hormone or IGF-I to pregnant rats on a reduced diet throughout pregnancy does not prevent fetal intrauterine growth retardation and elevated blood pressure in adult offspring.

Increasing evidence from human epidemiological studies suggests that poor growth before birth is associated with postnatal growth retardation and the development of cardiovascular disease in adulthood. We have shown previously that nutritional deprivation in the pregnant rat leads to intrauterine growth retardation (IUGR), postnatal growth failure, changes in the endocrine parameters of the somatotrophic axis, and to increased blood pressure in later life. In the present study, we investigated whether administration of insulin-like growth factor-I (IGF-I) or bovine growth hormone (GH) during pregnancy could prevent IUGR and/or alter long-term outcome. Dams from day 1 of pregnancy throughout gestation received a diet of ad libitum available food or a restricted dietary intake of 30% of ad libitum fed dams. From day 10 of gestation, dams were treated for 10 days with three times daily subcutaneous injections of saline (100 microl), IGF-I (2 micrograms/g body weight) or GH (2 micrograms/g body weight). Maternal weight gain was significantly increased (P<0.001) in ad libitum fed dams treated with GH, (98.9+/-4.73 g) compared with the IGF-I (80.5+/-2.17 g) and saline-treated (70.7+/-2.65 g) groups. There was a small increase in maternal weight gain (P<0.06) in 30% ad libitum fed dams following GH (16.3+/-2.47 g) and IGF-I (15.8+/-1.97 g) treatment compared with saline (9.2+/-1.96 g). Whole spleen, kidney and carcass weights were significantly (P<0.05) increased in ad libitum fed and 30% ad libitum fed dams with GH treatment. Circulating IGF-I was significantly increased (P<0.001) in ad libitum fed dams with both IGF-I (369.6+/-32.33 ng/ml) and GH (457.9+/-33.32 ng/ml) compared with saline treatment (211.7+/-14.02 ng/ml), and with GH (223.4+/-23.72 ng/ml) compared with saline treatment (112.0+/-7.33 ng/ml) in 30% ad libitum fed dams. Circulating GH binding protein (GHBP) levels were significantly reduced (P<0.05) in GH-treated (299.1+/-51.54 ng/ml) compared with saline-treated (503.9+/-62.43 ng/ml) ad libitum fed dams, but were not altered in 30% ad libitum fed dams. There was no significant effect of either IGF-I or GH treatment on fetal weight, placental weight, fetal organ weights or circulating IGF-I levels in both ad libitum fed and 30% ad libitum fed fetuses. Offspring of 30% ad libitum fed dams remained significantly growth retarded postnatally and showed elevated blood pressure in later life. The increased maternal weight gain following IGF-I or GH administration, without an effect on fetal and placental weights, suggests a modification in the mode of maternal nutrient repartitioning during mid to late pregnancy at the expense of the fetus.

Animals↗

PubMed1998

Fetal growth and placental function.

Fetal growth is largely determined by the availability of nutrients to the fetus. The fetus is at the end of a supply line that ensures delivery of nutrients from the maternal/uterine circulation to the fetus via the placenta. However, this supply line can not be regarded as a linear relationship. Maternal undernutrition will not only reduce global nutrient availability but will also influence the maternal and fetal somatotrophic axis. Both endocrine systems react in a very similar way to limited substrate supply. The hormones of the fetal somatotrophic axis, and in particular insulin-like growth factor (IGF)-1, are important regulators of fetal growth. Placental function is pivotal to materno-fetal nutrient and metabolite transfer. Placental function in turn, is heavily influenced by the maternal and fetal growth hormone (GH)-IGF-1 system. The placenta itself is also an active endocrine organ and it produces a large number of hormones including GH and IGF-1 as well their corresponding receptors. Thus the placenta can no longer be considered merely a passive conduit for fetal nutrition. Rather, it is actively involved in the integration of nutritional and endocrine signals from the maternal and fetal somatotrophic axes.

Animal Nutritional Physiological Phenomena↗

PubMed1998

Consequences of maternal undernutrition for fetal and postnatal hepatic insulin-like growth factor-I, growth hormone receptor and growth hormone binding protein gene regulation in the rat.

The mechanisms that contribute to postnatal growth failure following intrauterine growth retardation (IUGR) are poorly understood. We demonstrated previously that nutritional deprivation in the pregnant rat leads to IUGR in offspring, postnatal growth failure and to changes in endocrine parameters of the somatotrophic axis. The present study examines the effects of maternal undernutrition (30% of the ad libitum available diet; IUGR group) throughout pregnancy on hepatic insulin-like growth factor-I (IGF-I), growth hormone receptor (GHR) and GH-binding protein (GHBP) gene expression using solution hybridisation/RNase protection assays (RPAs). Animals were killed at fetal (E22, term=23 days) and postnatal (birth, days 5, 9, 15, 21) ages, livers were collected and RNA extracted for RPAs. Results demonstrate the presence of all IGF-I mRNAs resulting from transcription start sites (ss) in exon 1 (ss1/2, ss3, ss2 spliced), exon 2, the two IGF-I E-domain variants (Ea and Eb) as well as GHR and GHBP mRNAs in hepatic tissue at E22 in both the ad libitum fed and IUGR offspring. In the postnatal liver, IGF-I ss1/2, ss3, ss2 spliced, Ea and Eb IGF-I variants as well as GHR and GHBP mRNA transcripts increased in abundance from birth to day 21. IGF-I exon 2 transcripts were relatively constant from E22 until postnatal day 15, then increased at postnatal day 21 in both the ad libitum fed and IUGR offspring. The expressions of all hepatic IGF-I leader exon ss and Ea domain variants were significantly reduced in IUGR offspring (P<0.05) from E22 to postnatal day 9. In contrast, relative abundance of hepatic IGF-I Eb variants, GHR and GHBP mRNAs were unaltered in IUGR offspring compared with the ad libitum fed animals. Whether these postnatal effects of undernutrition are a direct consequence of IUGR or whether they are related, in part, to differences in postnatal food intake remains to be investigated. In summary, we have demonstrated that hepatic IGF-I ss within exon 1 and exon 2 are coordinately regulated. Use of exon 1 ss increased during normal development and decreased with IUGR without changes in GHR or GHBP gene expression. Eb transcripts, thought to represent GH-dependent endocrine regulation of IGF-I, were unchanged in IUGR. These results suggest a possible postreceptor defect in GH action as a consequence of IUGR.

Aging↗

PubMed1996

Chronic maternal undernutrition in the rat leads to delayed postnatal growth and elevated blood pressure of offspring.

To determine the effects of chronic maternal undernutrition on postnatal somatic growth and blood pressure, pregnant dams were randomly assigned to one of two dietary treatment groups. A control group was fed ad libitum throughout pregnancy and a restricted group was fed 30% of ad libitum intake. From birth, feeding was ad libitum in both groups, and litter size was adjusted to eight pups per litter. Litter size was not significantly altered by the reduced maternal intake. Offspring of the restricted fed group were significantly smaller than offspring from the ad libitum fed group from birth until 12 wk of age, but by 30 wk had similar body weights. Blood pressure was measured by tail cuff plethysmography. Offspring from the restricted fed group were found to have significantly (p < 0.05) elevated systolic blood pressure (5-8 mm Hg) at 30, 48, and 56 wk of age. These data demonstrate that nutritional deprivation in the pregnant rat leads to changes in postnatal allometric growth patterns, to delayed catch-up growth, and to elevated blood pressure in adulthood. The data are consistent with the hypothesis that poor maternal nutrition in pregnancy may irreversibly alter programming of the development of cardiovascular homeostasis.

Animals↗

PubMed1996

A model of intrauterine growth retardation caused by chronic maternal undernutrition in the rat: effects on the somatotrophic axis and postnatal growth.

While it is well established that severe maternal undernutrition during pregnancy causes intrauterine growth retardation (IUGR), there has been relatively little study of the endocrine consequences and postnatal development of growth-retarded offspring. We have developed a model in the rat of IUGR by nutritional restriction of the mother throughout gestation and have examined the effects of fetal growth retardation on the endocrine and metabolic status during the perinatal period. Timed matings were performed in Wistar rats and dams were randomly assigned to one of two dietary treatment groups. Food was available ad libitum throughout pregnancy to a control group (at libitum group) and a restricted group was fed 30% of the ad libitum intake (restricted fed group). After birth, food was available ad libitum in both groups and litter size was adjusted to eight pups per litter. Dams lost a significant amount of body weight throughout gestation due to undernutrition but were able to catch up to the ad libitum group by day 10 postnatally. Litter size was not affected by maternal undernutrition. Maternal plasma IGF-I levels were significantly reduced in the restricted fed group throughout gestation (P < 0.001) but were not different postnatally. Maternal plasma IGF-binding proteins (IGFBPs)-1, -2 and -3 were significantly (P < 0.05) increased in the restricted fed dams. The mean body weights of fetuses in late gestation from the restricted fed dams were significantly lower (P < 0.001) in comparison with fetuses from control dams. Placental weights were also significantly (P < 0.01) reduced in the restricted fed compared with control dams. Body weights were significantly lower in the offspring of restricted fed dams than control dams from birth (P < 0.01) until 90 days of age (P < 0.05). Nose-rump length was reduced in the fetuses of the restricted fed group at day 22 of gestation (P < 0.001) until weaning (P < 0.05). Plasma IGF-I levels were significantly reduced in the pups of restricted fed dams from day 22 of gestation (P < 0.01) until postnatal day 9 (P < 0.05) but were not significantly different at the later time-points. Plasma insulin levels were significantly reduced in the pups of restricted fed dams at birth (P < 0.05) but not at later time-points. Plasma IGFBP-1 and -2 levels were significantly increased in the offspring from restricted fed dams at day 22 of gestation, at birth and at day 9 postnatally (P < 0.05). 125I-Bovine GH specific binding to liver membranes was significantly lower (P < 0.05) in offspring from restricted fed dams at 21 days of age but not at 90 days of age. These data demonstrate that nutritional deprivation in the pregnant rat leads to IUGR and postnatal growth failure and to changes in allometric growth patterns and endocrine parameters of the somatotrophic axis postnatally.

Animals↗

PubMed1993

Potentiation of insulin-like growth factor-I (IGF-I) activity by an antibody: supportive evidence for enhancement of IGF-I bioavailability in vivo by IGF binding proteins.

The effects of ovine polyclonal antibodies raised against human recombinant IGF-I were investigated in GH-deficient rodents in vivo both in the presence and absence of exogenous IGF-I. Dwarf mice (negligible endogenous serum IGF-I) treated with anti-IGF-I serum which had been pre-incubated with IGF-I exhibited a significantly greater rate of daily weight gain than did mice treated with the same dose of IGF-I alone (P < 0.001) or even a 2.5-fold higher dose (P < 0.001). Similar increases in whole body weight gain were observed in dwarf rats, with a concomitant increase in dissected muscle weight. Serum IGF-I concentrations were greater in all animals treated with the complex of anti-IGF-I antibodies and IGF-I than in those administered only IGF-I. Size exclusion chromatography of dwarf rat serum indicated the presence of high mol wt material (> 160 kDa) capable of binding 125I-IGF-I in the anti-IGF-I treated rats. We suggest that this particular polyclonal antibody is behaving in a similar manner to an enhancing IGF binding protein, maintaining a reservoir of bioactive IGF-I. Since the antibody has a slightly lower affinity (2 x 10(8) liters/M) than that of the type 1 receptor, these data provide tentative indirect evidence to support the hypothesis that the recently discovered mechanisms which apparently decrease the affinities of several IGFBPs may indeed result in increased IGF-I bioavailability.

Animals↗

PubMed1991

The effect of the frequency of subcutaneous insulin-like growth factor-1 administration on weight gain in growth hormone deficient mice.

To ascertain the frequency of subcutaneous IGF-1 administration necessary to promote growth we examined the weight gain of male homozygous lit/lit mice in response to either sc. IGF-1 or bovine GH administration. Lit/lit mice showed a dose dependent response to treatment with GH. Bovine GH induced a response in body weight gain within 3 days of the start of treatment. Following a single subcutaneous injection of IGF-1, plasma IGF-1 levels were elevated for 4-6 hours. Three treatment schedules for IGF-1 were used (once daily, twice daily and four times daily), each employing the same total daily dose of IGF-1 (30 micrograms). With IGF-1 treatment, a significant effect on body weight gain was obtained when administered four times daily. The growth rate with IGF-1 treatment 6 hourly was similar to that observed following treatment with bGH (10 micrograms sc daily). Twelve hourly IGF-1 administration only had a significant effect on body weight gain when weight was measured in the evening. Lit/lit mice treated once daily with 30 micrograms IGF-1 had no weight gain response and became severely hypoglycaemic. Frequent subcutaneous IGF-1 administration is one approach to growth enhancement in GH deficiency; higher doses administered less frequently do not promote growth and may cause hypoglycaemia.

Animals↗