Inhibitory effects of 17 beta-estradiol and progesterone on ovarian carcinoma cell proliferation: A potential role for inducible nitric oxide synthase

Objectives. Indirect evidence suggests that estrogen and progesterone are i nvolved in the etiology of ovarian cancer (Oca). Estrogen and progesterone are also thought to modulate nitric oxide (NO) in human ovarian tumor tissu e via regulation of inducible nitric oxide synthase (iNOS). Objectives in t his study were: (1) to investigate the effects of 17 beta -estradiol (E-2) and progesterone (P-4) on Oca cell proliferation employing elevated hormone concentrations occurring within the microenvironment of the ovary, and (2) to determine whether E-2 or P-4 affects iNOS expression and NO generation in Oca cells. Methods. Proliferation assays assessed the effects of E-2 and P-4 on cell g rowth in three human Oca cell lines (HOC-7, OVCAR-3, SKOV-3). Reverse trans criptase polymerase chain reaction was used to assess mRNA expression and W estern blots to determine protein levels. NO generation was determined via the Griess reaction. Results. Elevated E-2, P-4, or E-2 plus P-4 (E + P), significantly inhibite d HOC-7 cells and OVCAR-3 cells, but not SKOV-3 cells. E-2 at 10 muM downre gulated iNOS expression and significantly reduced NO production in HOC-7 ce lls, while 10 muM P-4 or 10 muM E + P increased iNOS expression and NO prod uction. Conclusions. Our findings demonstrate that elevated E-2, P-4, or E + P resu lts in significant growth inhibition of Oca cells, and we propose a role fo r iNOS and NO in how these hormones modulate their activities in Oca cells. (C) 2001 Academic Press.