Progesterone Receptor-Mediated Inhibition of Apoptosis in Granulosa Cells Isolated from Rats Treated with Human Chorionic Gonadotropin1

Svensson, Elisabeth; Markström, Emilia; Andersson, Michael; Billig, Håkan

doi:10.1095/biolreprod63.5.1457

Cited by 69 publications

(38 citation statements)

References 44 publications

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“…This is interesting in that granulosa cell apoptosis occurs most frequently in small antral follicles [33], when PAIRBP1 levels are low or nondetectable. As the follicles develop into preovulatory follicles in response to eCG, the rate of granulosa cell apoptosis decreases [17,30]. This lower incidence of apoptosis observed in eCG-induced developing follicles correlates with the increased expression of PAIRBP1.…”

Section: Discussionmentioning

confidence: 95%

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Expression and Function of PAIRBP1 Within Gonadotropin-Primed Immature Rat Ovaries: PAIRBP1 Regulation of Granulosa and Luteal Cell Viability1

Peluso

Pappalardo

Lösel

et al. 2005

Biology of Reproduction

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The protein PAIRBP1, which was initially referred to as RDA288, is involved in mediating the antiapoptotic action of progesterone (P4) in spontaneously immortalized granulosa cells (SIGCs). The present studies were designed to assess the expression and function of PAIRBP1 in the different cell types within the immature rat ovary. Western blot analysis detected PAIRBP1 within whole-cell lysates of immature rat ovaries. Equine gonadotropin (eCG) induced a 3-fold increase in ovarian levels of PAIRBP1. Moreover, human chorionic gonadotropin (hCG), given 48 h after eCG, maintained these elevated levels for up to 4 days. Immunohistochemical analysis confirmed this and further demonstrated that interstitial, thecal, and surface epithelial cells also expressed PAIRBP1. The level of PAIRBP1 in these cells was not influenced by gonadotropin treatment. In contrast, eCG stimulated an increase in PAIRBP1 within the granulosa cells of the developing follicles. Treatment with hCG induced ovulation and ultimately the formation of corpora lutea (CL). High levels of PAIRBP1 expression were also observed within the luteal cells. Immunocytochemical studies on living, nonpermeabilized granulosa and luteal cells revealed that some PAIRBP1 localized to the extracellular surface of these cells. The presence of PAIRBP1 on the extracellular surface was consistent with the observation that an antibody to PAIRBP1 attenuated P4's antiapoptotic action in both granulosa and luteal cells. Although the PAIRBP1 antibody attenuated P4's action, it did not reduce the capacity of cells to specifically bind (3)H-P4. Immunoprecipitation with the PAIRBP1 antibody pulled down the membrane P4 binding protein known as progesterone receptor membrane complex-1 (PGRMC1; rat homolog accession number AJ005837). Taken together, these findings suggest that gonadotropins regulate the expression of PAIRBP1 in granulosa and luteal cells and that PAIRBP1 plays an important role in mediating P4's antiapoptotic action in these ovarian cell types. The exact mechanism of PAIRBP1's action remains to be elucidated, but it may involve an interaction with PGRMC1.

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Section: Discussionmentioning

confidence: 95%

“…P4 prevents apoptosis of granulosa cell isolated from follicles before [1,15,16] as well as after the LH surge [17,18]. Importantly, only granulosa cells isolated after the LH surge express nPR [14,18].…”

Section: Introductionmentioning

confidence: 99%

Expression and Function of PAIRBP1 Within Gonadotropin-Primed Immature Rat Ovaries: PAIRBP1 Regulation of Granulosa and Luteal Cell Viability1

Peluso

Pappalardo

Lösel

et al. 2005

Biology of Reproduction

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“…Indeed, in the PR-knockout (PRKO) mouse, mature follicles do not ovulate or luteinise but persist, giving the ovaries a polycystic appearance (Lydon et al 1995). PR expression and activation are involved in regulating rat granulosa cell susceptibility to apoptosis after LH receptor stimulation (Svensson et al 2000). PRs are required specifically for LHdependent follicular rupture leading to ovulation (Lydon et al 1995).…”

Section: Discussionmentioning

confidence: 99%

Disruption in the expression and immunolocalisation of steroid receptors and steroidogenic enzymes in letrozole-induced polycystic ovaries in rat

Zurvarra

Salvetti

Mason

et al. 2009

Reprod. Fertil. Dev.

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The objective of the present study was to characterise the expression and tissue distribution of steroid receptors (oestrogen receptor-alpha and -beta (ERalpha, ERbeta), androgen receptor (AR) and progesterone receptor (PR)) and steroidogenic enzymes (P450 aromatase (P450arom), 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and steroidogenic acute regulatory protein (StAR)) in letrozole-induced polycystic ovaries of rats. Changes in serum hormone levels, protein expression in whole ovaries by western blot analysis and protein localisation by immunohistochemistry were determined in female rats treated with the aromatase inhibitor letrozole and compared with controls in proestrous and diestrous rats. Increases in the serum LH, FSH and testosterone concentrations were observed in letrozole-treated rats whereas serum oestradiol and progesterone levels were reduced. Protein expression as analysed by western immunoblot was consistent with the immunohistochemical data. Letrozole treatment induced an increase in the expression of AR, StAR and 3beta-HSD and a decrease in ERbeta. ERalpha, PR and P450arom showed partial changes in relation to some cycle stages. These results indicate that cystogenesis in this experimental model is characterised by changes in steroid receptors and steroidogenic enzyme expression that may be essential to proper ovarian functioning and are in agreement with similar changes observed in women with PCOS.

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“…Researches have shown us that PR is expressed by granulosa cells just prior to the ovulation (Natraj and Richards, 1993;Park and Mayo, 1991). So, we can assume that it inhibits apoptosis of the granulosa cells isolated during the periovulatory period (Svensson et al, 2000). Recent evidence demonstrate that progesterone controls apoptosis by maintaining low basal intracellular calcium ion levels via membrane initiated events (Peluso et al, 2001a, b;Peluso, 2003).…”

Section: Gumus Et Al 59mentioning

confidence: 99%

Role of apoptosis-related factors in follicular atresia

Gumus¹,

Kılıç²,

Zülfikaroğlu³

2013

Int. J. Genet. Mol. Biol.

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Follicular atresia is the term used for the fate of follicles which undergo degenerative changes before rupturing during ovulation. Recent studies suggest that granulosa cell apoptosis play a major role in follicular atresia. The factors which lead the cell to apoptosis and which protect the cell death, still remain complicated and more studies are needed to elucidate the whole process. Here in this review, we aimed to simplify the factors and mechanisms taking place in granulosa cell apoptosis, to make the process more understandable.Key words: Granulosa cell, apoptosis, follicular atresia. INTRODUCTİONWhen a female human embryo is 8-week-old, she has 600,000 germ cells in her gonads and this number increases to 6 to 7 million at 20 weeks of gestation. But with the increasing rate of atresia, the number declines progressively and 1 million oocytes are present in the newborn, whereas 300,000 oocytes remain in puberty, of which approximately 400 will ovulate during the fertile lifespan (Oktem and Oktay, 2008;Gougeon, 1996;Matova and Cooley, 2001).'Follicular atresia' term is used to define antral follicles undergoing degenerative changes before rupturing during ovulation. It is initiated within the granulosa cell layer and subsequently in the theca cells Hsueh et al., 1994). In mammals, the basic mechanism of follicular atresia is apoptosis (Depalo et al., 2003). Apoptosis is a way which multicellular organisms use to eliminate unwanted cells in response to developmental signals or toxic stimuli (Quirck et al., 2004). It is regulated at the level of transcription or translation (Manabe et al., 2008). Major morphological characteristics of apoptosis are the internucleosomal DNA fragmentation, cell shrinkage, plasma membrane blebbing, and the apoptotic body formation (Schwartzman and Cidlowski, 1993).Granulosa cells possess endogenous pathways to trigger apoptosis, that are inhibited in the presence of survi-*Corresponding author. E-mail: zebru33@gmail.com. Tel: +90 (312) 2158652. Fax: +90 (312) 3124931.val factors (Quirck et al., 2004). To date, many apoptosisrelated factors have been implicated in follicular atresia, including death ligands and receptors, Bcl-2 family proteins, Nodal, caspases, growth factors, gonadotropins, and calcium. In this report, we will overview these factors one by one. Proapoptotic regulators in the cell death receptorligand systemDeath receptors constitute a subgroup within the tumor necrosis factor (TNF) receptor family. They are located on the cell surface, anchored to the cell membrane, are trimerized and have cytoplasmic death domains (DDs) which are necessary to induce apoptosis (Park et al., 2005;Ashkenazi and Dixit, 1998;Wallach et al., 1999). Fas receptor, TNF receptor, and TNF related apoptosis inducing ligand receptors (TRAILr) are the members of TNF receptor family that are found to have roles in follicular atresia in mammalian ovaries (Park et al., 2005).In most of the cases, the cell death receptor-mediated apoptosis takes place as follows:1) The cell death ligand binds to...

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Progesterone Receptor-Mediated Inhibition of Apoptosis in Granulosa Cells Isolated from Rats Treated with Human Chorionic Gonadotropin1

Cited by 69 publications

References 44 publications

Expression and Function of PAIRBP1 Within Gonadotropin-Primed Immature Rat Ovaries: PAIRBP1 Regulation of Granulosa and Luteal Cell Viability1

Expression and Function of PAIRBP1 Within Gonadotropin-Primed Immature Rat Ovaries: PAIRBP1 Regulation of Granulosa and Luteal Cell Viability1

Disruption in the expression and immunolocalisation of steroid receptors and steroidogenic enzymes in letrozole-induced polycystic ovaries in rat

Role of apoptosis-related factors in follicular atresia

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