Effect of Reproductive Hormones on Ovarian Epithelial Tumors: I. Effect

Abstract

We examined the effects of the 4 major female reproductive hormones, estradiol (E2), progesterone (P4), follicle stimulating hormone (FSH), and luteinizing hormone (LH) on thymidine incorporation in benign and malignant ovarian epithelial tumors cultured in vitro. Treatment of these tumors with E2, FSH and LH resulted in increased thymidine incorporation while treatment with P4 inhibited growth as well as thymidine incorporation. The inhibitory effect of progesterone could not be reproduced by treating the cells with ligands for other steroid hormone receptors known to interact with P4 such as the mineralocorticoid and glucocorticoid receptors. All cells lines expressed at least the PR-A isoform of the progesterone receptor. ORG2058, R5020, RU486, and ZK98299 acted as progesterone receptor agonists with regard to their effect on thymidine incorporation. P4 down-regulated cyclin B1 expression and cdk1 activity and up-regulated the p21 and p27 proteins. Expression of a reporter gene downstream to an AP-1 responsive element in a plasmid construct transfected into ovarian epithelial tumor cells was induced by P4 and inhibited by RU486. We conclude that P4 inhibits cell cycle activity in ovarian epithelial tumors, in part via down-regulation of the cdk1/cyclin B complex. This inhibitory effect may have therapeutic utility against ovarian epithelial tumors.

Quantitative analysis of follicle‐stimulating hormone receptor in ovarian epithelial tumors: A novel approach to explain the field effect of ovarian cancer development in secondary mullerian systems

“…12 FSH, but not LH, stimulates OET cell growth by upregulating cyclin B1 expression. 13 We concluded that FSH and LH have different and often opposing roles in ovarian epithelial tumorigenesis. In addition, we have also shown that gonadotropin receptors (FSHR and LHR) are present in OSE, OEIs and a majority of OETs, including borderline tumors and OECs in peritoneal counterparts.…”

“…Extracted total RNA was reverse-transcribed as described previously. 14,19 Samples were incubated at 37°C for 1 hr in 20 l of 10 mM TRIS (pH 8.4), 50 mM KCl, 2 mM MgCl 2 , 1 mM DTT, 5 units of ribonuclease inhibitor, 0.5 mM dNTP, 100 pmol of oligo-d(T) [12][13][14][15][16][17][18] and 200 units of MMLV reverse transcriptase (USB, Cleveland, OH). The reaction was terminated by heating for 5 min at 95°C.…”

Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype: results from the ovarian cancer association consortium pooled analysis

“…Studies in macaques suggest an apoptotic effect of progestins on the surface of the ovary (Rodriguez et al, 1998). In vitro treatment of both benign and malignant ovarian tumour cells with progestins results in an antiproliferative response (Zhou et al, 2002).…”

Hormone Therapy for the Treatment of Patients with Malignant Salivary Gland Tumor (MSGT)

“…A recent study, however, suggested that this problem can be circumvented by co-administering progestin and estrogen (Pearce et al, 2009). Further, experiments in culture showed that progesterone reduced the proliferation of both benign and malignant ovarian tumor cells (Zhou et al, 2002). Therefore, progestin might be a key factor for preventing and suppressing ovarian cancer cell growth.…”