Inhibitory effects of 17β-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 involved in the etiology of ovarian cancer (Oca). Estrogen and progesterone are also thought to modulate nitric oxide (NO) in human ovarian tumor tissue via regulation of inducible nitric oxide synthase (iNOS). Objectives in this 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 growth in three human Oca cell lines (HOC-7, OVCAR-3, SKOV-3). Reverse transcriptase polymerase chain reaction was used to assess mRNA expression and Western 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 inhibited HOC-7 cells and OVCAR-3 cells, but not SKOV-3 cells. E-2 at 10 muM downregulated iNOS expression and significantly reduced NO production in HOC-7 cells, while 10 muM P-4 or 10 muM E + P increased iNOS expression and NO production. Conclusions. Our findings demonstrate that elevated E-2, P-4, or E + P results in significant growth inhibition of Oca cells, and we propose a role for iNOS and NO in how these hormones modulate their activities in Oca cells. (C) 2001 Academic Press.