Overexpressed growth hormone (GH) synergistically promotes carcinogen-initiated liver tumour growth by promoting cellular proliferation in emerging hepatocellular neoplasms in female and male GH-transgenic mice.
OBJECTIVE
Growth hormone (GH), when overexpressed in male and female GH-transgenic mice, is known to induce liver tumours within 1 year. This study aimed to gain a clearer understanding of the interaction between GH and tumour cells in vivo.


RESULTS
The carcinogen diethylnitrosomine (DEN) was administered to neo-natal transgenic and non-transgenic mice maintained in a "hepatocarcinogenesis resistant" genetic background (C57BL/6J). Macroscopic, microscopic and liver weight/body weight ratio analyses revealed that carcinogen-induced hepatocarcinogenesis was dramatically accelerated in young GH-transgenic mice compared to non-transgenic counterparts. Image analysis of microscopic hepatocellular neoplasms showed rapidly increasing tumour burdens, and neoplastic foci size over time in young adult GH-transgenic mice. The magnitude of enhanced tumour growth was equivalent in both male and female transgenic mice, whereas much lower and sexually dimorphic tumour growth rates (males>females) were observed in non-transgenic mice treated with DEN. BrdU labelling experiments demonstrated that rapid tumour growth in carcinogen-treated GH-transgenic mice was due to the promotion of cell proliferation in emerging lesions. Tumour cell proliferation in young GH-transgenic mice was 2.6- and 4-fold higher, respectively, than that observed in similar age male and female non-transgenic mice. Interestingly, both GH-transgenic and non-transgenic mice displayed progressively slower tumour growth rates in older animals.


CONCLUSIONS
Overall, GH synergistically promotes carcinogen-induced hepatocarcinogenesis in both sexes of GH-transgenic mice by stimulating tumour cell proliferation.
Snibson
K J
KJ
Centre for Animal Biotechnology, School of Veterinary Science, Victoria 3010, Australia. kenjs@rubens.its.unimelb.edu.au
Bhathal
P S
PS
Adams
T E
TE
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000032:analysis / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004052:Diethylnitrosamine / Q000633:toxicity; D005260:Female; D020518:Focal Nodular Hyperplasia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013006:Growth Hormone / Q000096:biosynthesis* / Q000235:genetics; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009929:Organ Size / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
D004052:Diethylnitrosamine; D013006:Growth Hormone; D001973:Bromodeoxyuridine