Evidence of in situ estrogen synthesis in nitrosomethylurea-induced rat mammary tumors via the enzyme estrone sulfatase.
A variety of indirect evidence suggests that mammary tumors can synthesize free estrogens in situ via the sulfatase enzyme. The present study utilized an isotopic kinetic technique to provide direct confirmation of local tumor synthesis. Animals bearing nitrosomethylurea (NMU)-induced rat mammary tumors were infused with 14C-estrone as well as 3H-estrone sulfate and plasma:tissue gradients for each steroid measured. Liver, serving as a control tissue, uniformly synthesized free estrone from estrone sulfate with local synthesis in this organ providing an average of 78 +/- 1.0% of the estrone in this tissue. In rat mammary tumors, five out of seven synthesized estrone locally with individual values ranging from 19 to 50% synthesized in tissue. These data indicate that liver uniformly converts estrone sulfate to free estrone, whereas the majority, but not all, breast tumors synthesize estrogen locally via this pathway.
Masamura
S
S
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201, U.S.A.
Santner
S J
SJ
Santen
R J
RJ
D000818:Animals; D004967:Estrogens / Q000096:biosynthesis* / Q000097:blood; D004970:Estrone / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D008770:Methylnitrosourea / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013429:Sulfatases / Q000378:metabolism*
D004967:Estrogens; D004970:Estrone; D008770:Methylnitrosourea; D013429:Sulfatases; C020121:estrone sulfatase; C017296:estrone sulfate