Growth inhibition of estrogen-sensitive rat mammary tumors. Effect of an alpha-fetoprotein-secreting hepatoma.
The growth and regression patterns of estrogen (E)-sensitive mammary tumors (SNMU) and autonomous mammary tumors (ANMU) were studied in normal, castrated, and alpha-fetoprotein (AFP)-secreting and nonsecreting hepatoma-bearing female BUF rats. Both SNMU and ANMU tumors had comparable amounts of E receptor. SNMU tumors grew faster in female hosts than in male hosts. The latency period of SNMU tumors was lengthened when the tumor was inoculated into newborn hosts. These E-sensitive tumors regressed after castration of the adult hosts. Tumor regression was also observed in SNMU-bearing rats inoculated with AFP-secreting hepatomas. The growth pattern of the ANMU tumor was not affected by the sex or age of the host. Castration and inoculation of hepatomas to ANMU tumor-bearing rats did not result in regression of the ANMU tumors. We suggest that AFP inhibited the growth of E-sensitive cells in newborn and hepatoma 7777-bearing hosts. This inhibitory effect of AFP could not be attributed to a "functional castration" resulting from the trapping of 17 beta-estradiol (E2) by AFP, because the plasma levels of E2 in these animals affect levels of gonadotropins. Moreover, castration of hepatoma 7777-bearing rats resulted in increased plasma follicle-stimulating hormone and luteinizing hormones levels. The results strongly suggested that a) the malignant properties of E2-sensitive cells in adult hosts can be controlled by AFP, and b) the mechanism by which AFP inhibits the growth of E2-sensitive cells is independent of the E2 "trapping" phenomenon. An ontogenetic approach to the mechanism of action of estrogens may account for available results.
D000818:Animals; D000831:Animals, Newborn; D002369:Castration; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D008114:Liver Neoplasms, Experimental / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D009368:Neoplasm Transplantation; D051381:Rats; D011915:Rats, Inbred BUF; D011960:Receptors, Estrogen / Q000378:metabolism; D013997:Time Factors; D014184:Transplantation, Homologous; D000509:alpha-Fetoproteins / Q000097:blood / Q000378:metabolism*
D011960:Receptors, Estrogen; D000509:alpha-Fetoproteins; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone