Ovarian granulosa cell lines.

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9032, USA.
Molecular and Cellular Endocrinology (Impact Factor: 4.24). 01/2005; 228(1-2):67-78. DOI: 10.1016/j.mce.2004.04.018
Source: PubMed

ABSTRACT The ovary is a complex endocrine gland responsible for production of sex steroids and is the source of fertilizable ova for reproduction. It also produces various growth factors, transcription factors and cytokines that assist in the complex signaling pathways of folliculogenesis. The ovary possesses two primary steroidogenic cell types. The theca cells (and to a lesser extent, the stroma) are responsible for androgen synthesis, and the granulosa cells are responsible for conversion of androgens to estrogens, as well as progesterone synthesis. These cells undergo a transformation in the luteal phase of the menstrual cycle, converting them from estrogen producing, to predominantly progesterone producing cells. Understanding the molecular mechanisms regulating these cells is essential in understanding the regulation of steroidogenesis and reproduction. Creation of appropriate in vitro cell model systems can provide important tools for the study of ovarian function. This has led to the development of ovarian steroidogenic cell lines in several laboratories. Developing theca cell lines has met with limited success. Conversely, numerous human and animal granulosa cell lines have been developed. This review will discuss the existing granulosa cell lines and their characteristics.

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    ABSTRACT: Although endometriosis is suspected to be a cause of premature ovarian insufficiency (POI), the mechanism(s) underlying this process have not been elucidated. Recently, androgens were shown to promote oocyte maturation and to play a role in folliculogenesis. In addition, several reports have documented low testosterone levels in the follicular fluid obtained from endometriosis patients. We therefore examined whether the low levels of serum testosterone are associated with the apoptosis of granulosa cells in follicles obtained from endometriosis patients. Serum samples were collected from 46 patients with endometriosis and from 62 patients without endometriosis who received assisted reproductive therapy. Specimens of the ovaries obtained from 10 patients with endometrioma were collected using laparoscopy. The mean serum testosterone concentration in the patients with endometriosis was significantly lower than that observed in the patients without endometriosis. Furthermore, high expression of a pro-apoptotic Bcl-2 member, BimEL, in the follicles was found to be associated with a low serum testosterone level. We clarified the underlying mechanisms using a basic approach employing human immortalized granulosa cells derived from a primary human granulosa cell tumor, the COV434 cell line. The in vitro examination demonstrated that testosterone inhibited apoptosis induced by sex steroids depletion via the PI3K/Akt-FoxO3a pathway in the COV434 cells. In conclusion, we elucidated the mechanism underlying the anti-apoptotic effects of testosterone on granulosa cells, and found that a low-testosterone status is a potentially important step in the development of premature ovarian insufficiency in patients with endometriosis.
    PLoS ONE 12/2014; 9(12):e115618. · 3.53 Impact Factor
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    ABSTRACT: Chemotherapy treatment in women can frequently cause damage to the ovaries, which may lead to primary ovarian insufficiency (POI). In this study, we assessed the preventative effects of hyaluronic acid (HA) in immunosuppressive drug-induced POI-like rat models and investigated the possible mechanisms. We found that HA, which was reduced in primary and immunosuppressant-induced POI patients, could protect the immunosuppressant-induced damage to granulosa cells (GCs) in vitro. Then we found that HA blocked the tripterygium glycosides (TG) induced POI-like presentations in rats, including delayed or irregular estrous cycles, reduced 17 beta-estradiol(E2) concentration, decreased number of follicles, destruction of follicle structure, and damage of reproductive ability. Furthermore, we investigated the mechanisms of HA prevention effects on POI, which was associated with promotion of GC proliferation and PGRMC1 expression. In conclusion, HA prevents chemotherapy-induced ovarian damage by promoting PGRMC1 in GCs. This study may provide a new strategy for prevention and treatment of POI.
    Scientific reports. 01/2015; 5:7647.
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    ABSTRACT: Follicle stimulating hormone (FSH) plays a central role for in vitro fertilization therapy. Historically, FSH was extracted from urine of post-menopausal women. Now, most preparations used in Europe and North America are of recombinant origin. For the past several decades, the potency of FSH dosage has been determined by a single in vivo potency assay based on weight gain of rat ovaries upon hormonal treatment. This assay lacks precision, is cumbersome in interpretation, and sacrifices large numbers of rats. We herewith present the development and qualification of an alternative potency assay that will circumvent the aforementioned obstacles. The setup is based on a human ovary granulosa cell lines expressing the intact human FSH receptor on its surface. FSH binding results in induction of progesterone expression and secretion, which is subsequently quantitatively determined by a commercially available diagnostic ELISA. We demonstrate in this publication that the new assay features excellent precision and accuracy and has a wider working range than the in vivo assay. Analyses of commercial products of different origin using the in vitro assay confirm their stated potency. Further, it was demonstrated that the assay delivered comparable results to the Steelman/Pohley assay for a newly developed recombinant FSH product. The assay has been successfully validated for that product. Its accuracy, handling, and universal application for FSH preparations of different origin qualify the presented assay to complement and replace the Steelman/Pohley assay in the future.
    Altex Proceedings, 1/12, Proceedings of WC8, Montreal, Canada; 08/2011


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