Potent inhibitory effects of steroids in an in vitro model of angiogenesis

(Requests for offprints should be addressed to D C Jaggers) The regulation of angiogenesis in the ovarian follicle and corpus luteum is unclear. Steroids are produced at very high concentrations in these tissues and we therefore examined the effect of steroids on angiogenesis in vitro. Explants of rat aorta were embedded in collagen gel and cultured in serum-free medium. Capillary-like micro-vessels were produced from the explants and microvessel number and length were measured in the presence and absence of steroids. At a concentration of 10 \g=m\g/ml, cortisol, progesterone, 17\g=a\-hydroxyprogesteroneand medroxyprogesterone acetate produced degeneration of microvessels after 7 days of steroid treatment (P<0\m=.\01). Androstenedione and tetrahydro-S-(11-deoxytetrahydro\x=req-\ cortisol) (tetrahydro S) produced degeneration at a slower rate: androstenedione inhibited microvessel growth after 11 days (P<0\m=.\01)and tetrahydro S after 14 days (P<0\m=.\05). Oestriol had no effect on microvessels; oestrone had a slow degenerative effect with significant inhibition seen after 14 days (P<0\m=.\01).Oestradiol-17\g=b\at a concentration of 10 \g=m\g/mlcompletely inhibited microvessel growth from the explant cultures (P<0\m=.\01)while at 1 \g=m\g/mlit caused degenerative effects on growing microvessels. The effects of oestradiol and cortisol were reversible on removal of steroid-containing medium and replacement with 10% serum. We conclude that oestradiol may modulate angio-genesis in tissues in which the steroid concentration is high