Pituitary growth hormone (GH) is the major regulator of postnatal tissue growth and is capable of stimulating somatic growth in a dose dependant manner. GH is synthsised in the pituitary and released into the circulation under hypothalamic control. It was believed to act via a mediator, insulin-like growth factor-I (IGF-I) which was thought to be released by the liver in response to GH secretion. IGF-I was considered to distribute to other tissues via the general circulation, thus mediating the growth promoting effects of growth hormone. This sequence of events, known as the somatomedin hypothesis, was based on an inability to demonstrate both in vitro actions of GH and GH receptors in many tissues. At the time I commenced this PhD, the GH receptor had been demonstrated in the tibial growth plate, the skin, the gastrointestinal tract and the reproductive tract, by our group. In this study I have extended these GH receptor mapping studies to include the fetus and the central nervous system. In addition I have carried out a general study to distinguish between the localization of the GH receptor and localization of the alternatively spliced GH binding protein in the various tissues. This was not done in earlyer studies, since a specific antibody to the BP was not available. Finally, I chose a cell type expressing high levels of GH receptor in the adult, and showed a new role for GH, specifically, the regulation of intrinsic factor synthesis, which is stimulatd by GH independently of systemic IGF-1.Although fetal growth has been thought to be independent of pituitary GH, it is possible that pitutitary GH plays a modulatory role in organ development, or that a GH like substance of non pituitary origen may influence fetal growth through the GH receptor. Accordingly, I have used a variety of methods to study the ontogeny of the GH receptor/BPfrom the 12-day-old (E12) to the 18-day-old (E18) rat fetus. These methds were; immunohistochemistry. Northern blot analysis, reverse transcriptase polymerase chain reaction and solution hybridization-RNase protection assay. At E12 GH receptor was seen by immunohistochemistry largely in haemangioblastic tissues, and the presence of GH receptor mRNA was demonstrated by PCR and solution hybridization assay. A general increase in GH receptor/BP was evident from E12 to E18, with marked increase occurring between E16 and E18. By E18, GH receptor/BP immunoreactivity was observed in all major organ systems and was not prefemtially associated with any germ layer derivative. Haemangioblastic tissue was, however, strongly or intensely immunoreactive at all stages of development, as was the placenta, particularly the decidual cells. Most noteworhty of the other tissues expressing GH receptor/BP immunoreactivity by day 18 were skeletal and smooth muscle, epithelial lining cells, neuronal ganglia, ependymal cells and the adrenal cortex. Northern hybridization of total RNA with a [35S]-labelled rat GH receptor cRNA probe revealed that 3.9kb and 1.2kb transcripts complementary to the GH receptor riboprobe are present from at least El6. Solution hybridization assays demonstrated an exponential increase in the total embryonic GH receptor/BP mRNA during fetal development. Despite this incease, even by E18, levels were only 8% those of adult liver. In summary, I have demonstrated the presence and defined the ontogeny of the GH receptor/BP in the rat fetus from mid gestation onward. These results, when combined with earlier studies of GH action on fetal tissues mandate re-evaluation of the role of GH on prenatal growth.