INTRAHYPOTHALAMIC GROWTH-HORMONE FEEDBACK - FROM DWARFISM TO ACROMEGALY IN THE RAT

Two different dwarf rat models with primary (dw/dw, DW) or secondary ( transgenic growth retarded, WF/Tgr) GH deficiency and contrasting hypo thalamic GH-releasing hormone (GHRH) and somatostatin (SRIH) expressio n were implanted sc with GC cells. These form encapsulated rat GH-secr eting tumors that maintain high plasma rat GH levels for several weeks . In both strains, GC cell tumors stimulated growth and raised GHBP le vels, without affecting pituitary GH content. In DW rats, GC cell impl ants increased SRIH expression in the periventricular nucleus (PeV), b ut not in the arcuate nucleus (ARC), whereas their high GHRH expressio n in ARC was decreased by GC cells. In contrast, GC cell implants in W F/Tgr rats had little effect on the already high SRIH expression in Pe V or low GHRH expression in ARC, although they reduced SRIH expression in ARC. GC cell implants also reduced GH receptor expression in both ARC and PeV in the WF/Tgr dwarves. Thus, chronic GH overexposure stimu lates rapid growth in both dwarf strains, but has differential hypotha lamic effects in these models. This experimental approach now makes it possible to study the effects of pathophysiological concentrations of GH ranging from dwarfism to acromegaly in the same animal model.