EFFECT OF INTRAVENOUS-INFUSION OF GROWTH-HORMONE RELEASING HORMONE ONTHE MORPHOLOGY OF RAT PITUITARY SOMATOTROPHS

The effect of GRH infusion on rat adenohypophysial morphology was stud ied by light microscopy, immunocytochemistry, in situ hybridization, a nd electron microscopy. Synthetic rat GRH was intravenously administer ed by osmotic minipumps at 4.4, 72, 360 and 720 mug/day/rat for 1 week . In one group treated for 1 week with a daily dose of 720 mug GRH, th e rats were killed 7 days after withdrawal of GRH. Control rats in whi ch GRH was replaced by excipient, or those that received no treatment, were included as well. GRH infusion with daily doses of 360 and 720 m ug resulted in a significant increase in pituitary weight and weaker G H immunoreactivity compared with other groups. Ultrastructurally, the somatotrophs were increased in size and became sparsely granulated, an d the organelles involved in hormone sythesis were very prominent. The intensity of the GH mRNA signal did not differ from control animals, suggesting the desensitization of somatotrophs to GRH. The highest GRH dose induced an increased number of nuclei immunoreactive for prolife ration cell nuclear antigen (PCNA). One week after GRH withdrawal, shr inkage of cytoplasm, involution of RER and Golgi complex, and a decrea se of cell attachment sites indicated the reversibility of changes ind uced by GRH. In conclusion, GRH infusion induced, within days, hypertr ophy and proliferation of somatotrophs with ultrastructural features o f highly stimulated, sparsely granulated cells. Morphological changes were reversible.