EFFECTS OF INCREASING GESTATION, CORTISOL AND MATERNAL UNDERNUTRITIONON HYPOTHALAMIC NEUROPEPTIDE-Y EXPRESSION IN THE SHEEP FETUS

We have characterized the localization and the ontogenetic changes in Neuropeptide tyrosine (NPY) before birth and investigated the regulati on of NPY expression by cortisol and undernutrition in the fetal sheep hypothalamus during late gestation. Using immunohistochemistry, we ha ve identified NPY-containing neurons in the infundibular nucleus and t he internal layer of the median eminence in fetal hypothalami collecte d between 110 and 147 days gestation, NPY projections were also presen t in the paraventricular nucleus (PVN) of fetal hypothalami al all age s between 110 days gestation and term, There was a significant increas e in the amount of immunoreactive NPY/g hypothalamus between 87 and 11 3 days and 131-140 days gestation and a further significant increase a fter 141 days gestation. The total hypothalamic content of immunoreact ive NPY increased significantly between 87 and 113 days and 141-145 da ys gestation, The levels of NPY mRNA: 18S rRNA in the mediobasal regio n of the fetal hypothalamus were significantly higher at 145-146 days gestation than at any earlier gestational age between 116 and 141 days gestation. Cortisol (2.5-3.0 mg/24 h) was infused intrafetally betwee n 109 and 116 days gestation. The ratio of NPY mRNA: 18s rRNA in the m ediobasal region of the fetal hypothalamus was significantly higher in the cortisol-infused group when compared with the saline-infused cont rol group at 116 days gestation, Maternal, and hence fetal undernutrit ion, was induced between 110 and 146 days gestation, At 145-146 days g estation the ratio of NPY mRNA: 18S rRNA in the mediobasal region of t he fetal hypothalamus was significantly higher in the undernutrition g roup when compared with control animals, We have therefore demonstrate d that NPY is present in the hypothalamus of the sheep fetus before bi rth and that hypothalamic NPY content and NPY mRNA increase before del ivery. We have also found that glucocorticoids and undernutrition stim ulate increases in NPY mRNA levels in the hypothalamus before birth.