Strain differences and inheritance of angiogenic versus angiostatic activity in oestrogen-induced rat pituitary...

In this study we investigated the control of the angiogenic/haemorrhagic phenotype of oestrogen-induced rat pituitary tumours of an F1 hybrid (F1) of Fischer 344 (F344) (tumour susceptible) and Brown Norway (tumour resistant) strains. F1 forms a pituitary tumour upon chronic oestrogen treatment, but microvessel count (MVC) is no greater than untreated. In other words, F1 MVC keeps pace with tissue growth during growth of an oestrogen-induced tumour. On the other hand, F344 showed a significant increase in MVC (P = 0.002) upon chronic oestrogen treatment during growth of a large pituitary tumour. F1 control vasculature showed features intermediate between the parent strains, while oestrogen-treated F1 pituitary has pronounced changes commensurate with vascular remodelling or angiogenic activity, along with regressive changes. In addition, oestrogen-treated F1 does not form the haemorrhagic lakes characteristic of oestrogen-treated F344. We conclude that F1, which has a 50-50 genetic composition of the tumour susceptibility and tumour resistance alleles, shows loss of angiostatic activity in the absence of an effective angiogenic stimulus. As a result it is unable to make the 'switch' to the angiogenic phenotype.