ACUTE EFFECTS OF RAT GROWTH-HORMONE (GH), HUMAN GH AND PROLACTIN ON PROLIFERATING RAT-LIVER CELLS IN-VITRO - A STUDY OF MITOTIC BEHAVIOR AND ULTRASTRUCTURAL ALTERATIONS

Examination of livers from transgenic mice over expressing human growt h hormone (hGH) revealed numerous alterations including a striking inc idence of mitotic figures. The reason for increased proliferation is u nclear, but could be related to effects of hGH, which is also acting a s a lactogen in rodents. In order to identify some of the actions of G H, we have examined the effects of rat and human GH and rat prolactin on proliferation, as well as on morphological differentiation of norma l rat liver cells in vitro. These cells, isolated from a 20-day-old ra t, proliferate in culture, incorporate BrdU and are thus strikingly di fferent from primary cultures of isolated hepatocytes, which typically are non-proliferating cells.;Monolayers of these cells were treated w ith rat prolactin (rPRL), rat growth hormone (rGH), rPRL and rGH in co mbination, or hGH, for 24 hr. Subsequently, mitotic figures were count ed and the cultures were processed for transmission electron microscop y. The incidence of mitotic figures was significantly increased by rPR L (27.4%) versus control (19%), while rGH (13%) and hGH (9.6%) signifi cantly decreased proliferation. In controls. 2% of the proliferating c ells were in prophase, approximately 12% in metaphase and approximatel y 15% in telophase. In contrast, rPRL caused a significant increase in the number of cells in prophase (14%) and reduced the number of cells in the other mitotic stages. hGH and rGH reduced the overall number o f mitotic figures. Unexpectedly, the effects of rGH plus rPRL were dif ferent from the effect of hGH. In addition, each treatment caused dist inct morphological changes of liver cell organelles. Thus, after rPRL treatment mitochondria were generally large and bent, while rGH treatm ent was associated with irregularly shaped mitochondria and conspicuou s microtubule/microfilament arrangements. In contrast, after rPRL plus rGH treatment the chromatin pattern was altered. In summary, these re sults suggest specific hormone effects on both cell proliferation and metabolism as reflected by distinct changes in morphology. Unexpectedl y, the combined effect of rCH and rPRL were not identical to the effec ts of hGH, suggesting a possibility of a unique effect of hGH in this system.