title: Ontogeny and nutritional manipulation of the hepatic prolactin-growth hormone-insulin-like growth factor axis in the ovine fetus and in neonate and juvenile sheep.
abstract: The somatotrophic axis is the main endocrine system regulating postnatal growth; however, prenatal growth is independent of growth hormone (GH). Fetal development relies on the coordinated actions of a range of hormones, including insulin-like growth factors (IGF), and prolactin (PRL), in the control of differentiation, growth and maturation. In the sheep the abundance peaks for liver IGF-II and PRL receptors occur during late gestation while that for IGF-I receptor occurs at birth. All receptors, with the exception of GH receptor subsequently decrease by age 6 months. It has been proposed that maternal undernutrition during gestation regulates the maturation of the fetal hypothalmic-pituitary-adrenal axis and endocrine sensitivity. Critically, the timing of the nutritional insult may affect the magnitude of reprogramming. Maternal malnutrition during early to mid-gestation (3.2-3.8 MJ/d (60% total metabolisable energy requirements) v. 8.7-9.9 MJ/d (150% total metabolisable energy requirements) between 28 and 80 d of gestation) had no effect on body or liver weight. Nutrient-restricted (NR) fetuses sampled at 80 d (mid-gestation) showed up-regulation of hepatic PRL receptor, but following refeeding the normal gestational rise in PRL and GH receptors did not occur. Hepatic IGF-II receptor was down regulated in NR fetuses at both mid- and late gestation. Conversely, 6-month-old offspring showed no difference in the abundance of either GH receptor or PRL receptor, while IGF-II mRNA was increased. Offspring of ewes malnourished during late gestation (9.1 MJ/d (60% total metabolisable energy requirements) v. 12.7 MJ/d (100% total metabolisable energy requirements) from 110 d of gestation to term) showed reduced abundance of hepatic GH and PRL receptor mRNA. In conclusion, maternal undernutrition during the various stages of gestation reprogrammed the PRL-GH-IGF axis. Nutritional regulation of cytokine receptors may contribute to altered liver function following the onset of GH-dependent growth, which may be important in regulating endocrine adaptations during subsequent periods of nutritional deprivation.
authors.affiliation: Centre for Reproduction and Early Life, Institute of Clinical Research and Children's Brain Tumour Research Centre, University Hospital, Nottingham NG7 2UH, UK. mgxmah@nottingham.ac.uk
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Hyatt
authors.forename: David A
authors.initials: DA
authors.lastname: Walker
authors.forename: Terence
authors.initials: T
authors.lastname: Stephenson
authors.forename: Michael E
authors.initials: ME
authors.lastname: Symonds
mesh_terms: D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D005314:Embryonic and Fetal Development; D005260:Female; D013006:Growth Hormone / Q000502:physiology*; D008099:Liver / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D011247:Pregnancy; D011388:Prolactin / Q000502:physiology*; D012756:Sheep / Q000196:embryology / Q000254:growth & development*; D013002:Somatomedins / Q000502:physiology*
chemical_list: D013002:Somatomedins; D011388:Prolactin; D013006:Growth Hormone