Acute effects of rat growth hormone (GH), human GH and prolactin on proliferating rat liver cells in vitro: a study of mitotic behaviour and ultrastructural alterations.

Examination of livers from transgenic mice over expressing human growth hormone (hGH) revealed numerous alterations including a striking incidence of mitotic figures. The reason for increased proliferation is unclear, but could be related to effects of hGH, which is also acting as a lactogen in rodents. In order to identify some of the actions of GH, we have examined the effects of rat and human GH and rat prolactin on proliferation, as well as on morphological differentiation of normal rat liver cells in vitro. These cells, isolated from a 20-day-old rat, proliferate in culture, incorporate BrdU and are thus strikingly different from primary cultures of isolated hepatocytes, which typically are non-proliferating cells. Monolayers of these cells were treated with rat prolactin (rPRL), rat growth hormone (rGH), rPRL and rGH in combination, or hGH, for 24 hr. Subsequently, mitotic figures were counted and the cultures were processed for transmission electron microscopy. The incidence of mitotic figures was significantly increased by rPRL (27.4%) versus control (19%), while rGH (13%) and hGH (9.6%) significantly decreased proliferation. In controls, 2% of the proliferating cells were in prophase, approximately 12% in metaphase and approximately 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 of mitotic figures. Unexpectedly, the effects of rGH plus rPRL were different from the effect of hGH. In addition, each treatment caused distinct morphological changes of liver cell organelles.(ABSTRACT TRUNCATED AT 250 WORDS)