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: 4.41). 01/2005; 228(1-2):67-78. DOI: 10.1016/j.mce.2004.04.018
Source: PubMed


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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    • "The underlying mechanism for the observed increase in viable cell number in PCOS and metformin-pretreated GCs is unclear. The GCs from early antral follicles (0.5–2 mm in diameter) have the potential to proliferate in physiological, serum-free culture when stimulated appropriately, while cells from larger antral follicles (>5–6 mm in diameter) more commonly tend to differentiate if viable cell number is maintained in vitro, as evidence by their increased capacity to aromatize androgens to estrogens (Breckwoldt et al., 1996; Campbell et al., 1996; Havelock et al., 2004). The granulosa lutein cells used in the present experiments were predominantly harvested from larger antral follicles and, further, they were already terminally differentiated on collection following exposure to the hCG trigger in vivo. "
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    ABSTRACT: STUDY QUESTION What are the consequences of polycystic ovary syndrome (PCOS) pathology and metformin-pretreatment in vivo in women with PCOS on the metabolism and steroid production of follicular phenotype- and long-term cultured-granulosa cells (GC)?
    Human Reproduction 08/2014; 29(10). DOI:10.1093/humrep/deu187 · 4.57 Impact Factor
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    • "Although cell lines are technically easier to work with when compared with primary culture, the former may acquire different gene expression patterns and no longer represent the characteristics of the physiological cellular states, particularly when they are manipulated by a range of methods including co-or triple transfection either with oncogenes or tumor suppressor genes (Havelock et al., 2004). Moreover, the validation of the granulosa cell culture as a representative of the different developmental stage of the follicle was not established, and therefore, its use as a model for ovarian studies is limited (Havelock et al., 2004). "
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    ABSTRACT: Cell culture techniques of human mural granulosa cells (MGCs) serve as a major in vitro tool. However, the use of luteinized MGCs has major limitations due to their luteinized state. Our aim was to establish a standardized protocol for the culture of MGCs as a model for different stages of folliculogenesis. We showed that early-non-luteinized, preovulatory-non-luteinized and luteal-MGCs have distinct gene expression pattern. After 4 days of incubation of luteinized-MGCs, ovulatory genes mRNA's achieve expression levels similar to the early non-luteinized follicles. FSH stimulation for 48 hours of these 4 days cultured MGCs showed ovulatory genes mRNA's expression similar to the pre-ovulatory- non-luteinized follicles. These FSH-stimulated cells responded to hCG stimulation in a pattern similar to the response of pre-ovulatory follicles. This novel model may provide a standardized research tool for delineation of the molecular processes occurring during the latter stages of follicular development in the human ovary.
    Molecular and Cellular Endocrinology 02/2014; 384(1). DOI:10.1016/j.mce.2014.01.018 · 4.41 Impact Factor
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    • "Due to the relatively rare occurrence of GCTs, few human granulosa tumor cell lines have been established [44], [45]. The KGN and COV434 GCT cell lines are two useful cell lines for the study of GCTs because they retain many features of primary GCT cells [44], [45], [46]. The KGN cell line was derived from a 73-yr-old patient with a recurrent, metastatic GCT in the pelvic region [3], [44]. "
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    ABSTRACT: Granulosa cell tumors (GCTs) are the most common ovarian estrogen producing tumors, leading to symptoms of excessive estrogen such as endometrial hyperplasia and endometrial adenocarcinoma. These tumors have malignant potential and often recur. The etiology of GCT is unknown. TGFα is a potent mitogen for many different cells. However, its function in GCT initiation, progression and metastasis has not been determined. The present study aims to determine whether TGFα plays a role in the growth of GCT cells. KGN cells, which are derived from an invasive GCT and have many features of normal granulosa cells, were used as the cellular model. Immunohistochemistry, Western blot and RT-PCR results showed that the ErbB family of receptors is expressed in human GCT tissues and GCT cell lines. RT-PCR results also indicated that TGFα and EGF are expressed in the human granulosa cells and the GCT cell lines, suggesting that TGFα might regulate GCT cell function in an autocrine/paracrine manner. TGFα stimulated KGN cell DNA synthesis, cell proliferation, cell viability, cell cycle progression, and cell migration. TGFα rapidly activated EGFR/PI3K/Akt and mTOR pathways, as indicated by rapid phosphorylation of Akt, TSC2, Rictor, mTOR, P70S6K and S6 proteins following TGFα treatment. TGFα also rapidly activated the EGFR/MEK/ERK pathway, and P38 MAPK pathways, as indicated by the rapid phosphorylation of EGFR, MEK, ERK1/2, P38, and CREB after TGFα treatment. Whereas TGFα triggered a transient activation of Akt, it induced a sustained activation of ERK1/2 in KGN cells. Long-term treatment of KGN cells with TGFα resulted in a significant increase in cyclin D2 and a decrease in p27/Kip1, two critical regulators of granulosa cell proliferation and granulosa cell tumorigenesis. In conclusion, TGFα, via multiple signaling pathways, regulates KGN cell proliferation and migration and may play an important role in the growth and metastasis of GCTs.
    PLoS ONE 11/2012; 7(11):e48299. DOI:10.1371/journal.pone.0048299 · 3.23 Impact Factor
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