Growth stimulation of ovarian and extraovarian mesothelial cells by corpus luteum extract

Summary Ovarian (OM) and extraovarian (EM) mesothelia represent a common source of gynecologic malignancies with yet unclear pathogenesis. Ovulation triggers a finite wave of DNA synthesis and morphogenesis only in native OM cells, probably through the activation of intraovarian growth factors. To evaluate their growth response to such factors, OM and EM cells were obtained from estrous New Zealand white rabbits by enzymatic dispersion and unit gravity sedimentation. Cell cultures were maintained in serumless, fibronectin-rich, HL-1 medium without or with rabbit corpora lutea tissue extracts (CLE). The growth effects of CLE were evaluated by measuring percent changes in cell number relative to controls (CCN), cell population doublings (CPD), cell population doubling time in hours (CPDT). After 7.5 days, CLE enhanced (P<0.001) the growth of both OM and EM cells, which exhibited, respectively, a CCN of 214 and 257%; a CPD of 2.89 and 2.87; and a CPDT of 54.39 and 59.49. CLE-treated OM and EM cells were smaller, formed more cohesive monolayers, and exhibited more frequent and diffuse microvilli than control cells. These data show a similar in vitro response of OM and EM cells to luteal growth factors, suggesting that the lack of postovulatory morphogenesis in native extraovarian mesothelia is due to the spatially restricted activity of intraovarian growth factors.     

Apolipoprotein-E messenger RNA in rat ovary is expressed in theca and interstitial cells and presumptive macrophage, but not in granulosa cells.

Apolipoprotein-E (apoE) is a constituent of various lipoproteins and is a ligand for cellular lipoprotein receptors. Unlike most apolipoproteins, apoE is synthesized in peripheral tissues, including those engaged in steroidogenesis. ApoE expression in adrenal cells inhibits cholesterol utilization for steroid synthesis and blocks signal transduction via the protein kinase-A pathway. In cultured ovarian thecal/interstitial cells, exogenous apoE has been shown to inhibit LH-induced androgen synthesis. These findings support a role for apoE as an autocrine or paracrine factor involved in regulating steroidogenesis. In the present study in situ hybridization was used to identify cell types that express apoE mRNA in ovaries from rats with a 4-day estrous cycle, from pregnant rats, from immature rats treated with PMSG to stimulate follicular development, and from PMSG-treated rats that were subsequently administered hCG to stimulate ovulation and luteinization. ApoE mRNA was localized to theca and interstitial cells of follicles in animals at all stages of the estrous cycle as well as in immature rats treated with PMSG. ApoE mRNA was not detected in oocytes, cumulus cells, or granulosa cells. High levels of apoE mRNA also were expressed by localized clusters of presumptive macrophages in atretic follicles and degenerating corpora lutea. This complex pattern of expression may indicate that apoE has multiple functions in the rat ovary. ApoE made by theca and interstitial cells may act locally as an autocrine factor to regulate androgen production. ApoE made in atretic follicles and regressing corpora lutea may serve to facilitate local transport and reutilization of lipid released as these structures degenerate.