The effect of an aromatase inhibitor, 4-hydroxy-4-androstene-3,17-dione, on estrogen-dependent processes in reproduction and breast cancer.

Abstract

4-Hydroxy-f-androstene-3,17-dione (4-OH-A) when tested at various concentrations was found to inhibit markedly the conversion of 4-andorstene-3,17-dione to estrogens inhuman placental and rat ovarian microsomes. To obtain evidence that estrogen biosynthesis could also be reduced in vivo with 4-OH-A, rats were treated sc at a dose level of 50 mg/kg body weight. After 3 h the ovarian veins were cannulated and blood collected. Estradiol concentrations in the plasma were reduced by 80% compared to control values during the proestrous surge and on Day 4 of pregnancy. 4-OH-A was also found to be effective in controlling estrogen-dependent reproductive and neoplastic processes. In rats treated from Day 2-7 of pregnancy, implantation of fertilized ova was completely prevented in some rats, while in others either implantation was delayed or the development of implants was retarded. 4-OH-A treatment of rats having estrogen-dependent breast tumors induced by 7,12-dimethylbenz(a)anthracene caused 80% of the tumors to regress significantly in 4 weeks of treatment; 42% of these regressed completely.

• Authors: A M Brodie, W C Schwarzel, A A Shaikh, H J Brodie
• Journal: Endocrinology (Endocrinology) Vol. 100 Issue 6 Pg. 1684-95 (Jun 1977) ISSN: 0013-7227 [Print] United States
• PMID: 404132 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Aromatase Inhibitors
• Estrogens
• Androstenedione
• 9,10-Dimethyl-1,2-benzanthracene
• formestane

Topics

• 9,10-Dimethyl-1,2-benzanthracene
• Androstenedione (analogs & derivatives, metabolism, pharmacology, therapeutic use)
• Animals
• Aromatase Inhibitors
• Body Weight
• Embryo Implantation (drug effects)
• Estrogens (biosynthesis)
• Female
• Humans
• Male
• Mammary Neoplasms, Experimental (chemically induced, drug therapy)
• Pregnancy
• Proestrus
• Rats