scholarly journals Liver Receptor Homolog-1 and Steroidogenic Factor-1 Have Similar Actions on Rat Granulosa Cell Steroidogenesis

Endocrinology ◽  
2007 ◽  
Vol 148 (2) ◽  
pp. 726-734 ◽  
Author(s):  
Deeksha Saxena ◽  
Rosalba Escamilla-Hernandez ◽  
Lynda Little-Ihrig ◽  
Anthony J. Zeleznik
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Hydroxysteroid Dehydrogenase ◽  
Side Chain ◽  
Steroidogenic Factor 1 ◽  
Side Chain Cleavage ◽  
Progesterone Production ◽  
Chain Cleavage ◽  
Estrogen Production ◽  
Cleavage Enzyme

Granulosa cells express the closely related orphan nuclear receptors steroidogenic factor-1 (SF-1) and liver receptor homolog-1 (LRH-1). To determine whether SF-1 and LRH-1 have differential effects on steroid production, we compared the effects of overexpressing LRH-1 and SF-1 on estrogen and progesterone production by undifferentiated rat granulosa cells. Adenovirus mediated overexpression of LRH-1 or SF-1 had qualitatively similar effects. Neither LRH-1 nor SF-1 alone stimulated estrogen or progesterone production, but when combined with FSH and testosterone, each significantly augmented progesterone production and mRNAs for cholesterol side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase above that observed with FSH alone, with SF-1 being more effective than LRH-1. LRH-1 did not augment FSH-stimulated estrogen production, whereas SF-1 produced only a slight (∼30%) augmentation of FSH-stimulated estrogen production. The stimulatory actions of both were reduced by overexpression of dosage-sensitive sex reversal, adrenal hypoplasia congenita, critical region on the X chromosome, gene 1. Expression of either LRH-1 or SF-1 together with constitutively active protein kinase B in the absence of FSH stimulated progesterone production and mRNAs for 3β-hydroxysteroid dehydrogenase and cholesterol side-chain cleavage enzyme but did not stimulate estrogen production or mRNA for aromatase. These findings demonstrate that LRH-1 and SF-1 have qualitatively similar actions on FSH-stimulated estrogen and progesterone production, which would suggest that these factors may have overlapping actions in the regulation of steroidogenesis that accompanies granulosa cell differentiation.

scholarly journals Testosterone stimulates progesterone production and STAR, P450 cholesterol side-chain cleavage and LH receptor mRNAs expression in hen (Gallus domesticus) granulosa cells

Reproduction ◽  
2009 ◽  
Vol 138 (6) ◽  
pp. 961-969 ◽  
Author(s):  
P L Rangel ◽  
A Rodríguez ◽  
S Rojas ◽  
P J Sharp ◽  
C G Gutierrez
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Passive Immunization ◽  
Side Chain ◽  
Lh Receptor ◽  
Side Chain Cleavage ◽  
Progesterone Production ◽  
Chain Cleavage ◽  
Chicken Ovary ◽  
In Cells

The chicken ovary is organized into a hierarchy of yellow yolky follicles that ovulate on successive days. Active or passive immunization of laying hens against testosterone blocks ovulation without affecting follicle development. Testosterone may play a role in pre-ovulatory follicle maturation by stimulating granulosa progesterone production. We assessed whether this stimulus is dose-related and depends on the maturity of the donor follicle, and if it does so by stimulating granulosa cell STAR, P450 cholesterol side-chain cleavage (P450scc), and LH receptor (LHCGR) mRNAs expression. Progesterone production by granulosa cells from F1, F3, and F4 follicles, cultured for 3 h without testosterone was greater in cells collected 11–14 h than 1–4 h after ovulation. These differences in progesterone production were less pronounced after granulosa cells had been cultured for 24 h. Culture of granulosa cells for 3 or 24 h with testosterone (1–100 ng/ml) stimulated progesterone production in cells collected from F4, F3, or F1 follicles 1–4, or 11–14 h after ovulation. Testosterone (0–4000 ng/ml) alone or in combination with LH (0–100 ng/ml) increased progesterone production by F1 granulosa cells, collected 1–4 and 11–14 h after ovulation and cultured for 3 h. Finally, testosterone (10 or 100 ng/ml) increased STAR, P450scc, and LHCGR mRNAs, when added to 3 h cultures of F1 granulosa cells. In conclusion, testosterone stimulates granulosa cell progesterone production in hen pre-ovulatory hierarchical follicles irrespective of maturational state, acting alone or additively with LH. We propose that testosterone promotes granulosa cell maturation to facilitate the pre-ovulatory release of LH.

Insulin-like growth factor I enhancement of steroidogenesis by bovine granulosa cells and thecal cells: dependence on de novo cholesterol synthesis

1996 ◽  
Vol 151 (3) ◽  
pp. 365-373 ◽  
Author(s):  
L J Spicer ◽  
T D Hamilton ◽  
B E Keefer
Keyword(s):  
Granulosa Cells ◽  
Cholesterol Synthesis ◽  
De Novo ◽  
Side Chain ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Thecal Cells ◽  
Igf I ◽  
Cleavage Enzyme ◽  
Coa Reductase

Abstract Studies were conducted to determine the importance of de novo cholesterol synthesis and cholesterol side-chain cleavage enzyme in the action of IGF-I in bovine granulosa and thecal cells. Granulosa and thecal cells from bovine follicles were cultured for 2 days in 10% fetal calf serum and then treated with luteinizing hormone (100 ng/ml) and IGF-I (0 or 100 ng/ml) for an additional 2 days in serum-free medium. During the last 24 h of treatment, cells were concomitantly treated with simvastatin (0, 0·5 or 5 μg/ml) or 25-hydroxycholesterol (0 or 10 μg/ml). Simvastatin, a potent inhibitor of the key enzyme controlling de novo cholesterol synthesis, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, completely inhibited (P<0·05) progesterone production by granulosa cells and progesterone and androstenedione production by thecal cells. Simvastatin also inhibited (P<0·05) granulosa cell and thecal cell proliferation. Concomitant treatment with mevalonate, an immediate product of HMG-CoA reductase, attenuated the inhibitory effect of simvastatin on progesterone and androstenedione production by thecal cells and blocked the inhibitory effect of simvastatin on cell proliferation. The addition of 25-hydroxycholesterol, a substrate for cholesterol side-chain cleavage enzyme, had no effect (P>0·10) on IGF-I-stimulated progesterone or androstenedione production by thecal cells and actually inhibited (P<0·05) IGF-I-stimulated progesterone production by granulosa cells. These results provide indirect evidence indicating that stimulation of HMG-CoA reductase is an important locus of IGF-I action in bovine granulosa and thecal cells, whereas IGF-I has little or no effect on side-chain cleavage enzyme activity in these same cell types under the culture conditions employed. Journal of Endocrinology (1996) 151, 365–373

scholarly journals Prostaglandin E2 Via Steroidogenic Factor-1 Coordinately Regulates Transcription of Steroidogenic Genes Necessary for Estrogen Synthesis in Endometriosis

2009 ◽  
Vol 94 (2) ◽  
pp. 623-631 ◽  
Author(s):  
Erkut Attar ◽  
Hideki Tokunaga ◽  
Gonca Imir ◽  
M. Bertan Yilmaz ◽  
David Redwine ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Promoter Activity ◽  
Hydroxysteroid Dehydrogenase ◽  
Side Chain ◽  
Mrna Levels ◽  
Steroidogenic Factor 1 ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Estrogen Synthesis ◽  
Steroidogenic Genes

Abstract Context: Products of at least five specific steroidogenic genes, including steroidogenic acute regulatory protein (StAR), which facilitates the entry of cytosolic cholesterol into the mitochondrion, side chain cleavage P450 enzyme, 3β-hydroxysteroid-dehydrogenase-2, 17-hydroxylase/17-20-lyase, and aromatase, which catalyzes the final step, are necessary for the conversion of cholesterol to estrogen. Expression and biological activity of StAR and aromatase were previously demonstrated in endometriosis but not in normal endometrium. Prostaglandin E2 (PGE2) induces aromatase expression via the transcriptional factor steroidogenic factor-1 (SF1) in endometriosis, which is opposed by chicken-ovalbumin upstream-transcription factor (COUP-TF) and Wilms’ tumor-1 (WT1) in endometrium. Objective: The aim of the study was to demonstrate a complete steroidogenic pathway leading to estrogen biosynthesis in endometriotic cells and the transcriptional mechanisms that regulate basal and PGE2-stimulated estrogen production in endometriotic cells and endometrium. Results: Compared with normal endometrial tissues, mRNA levels of StAR, side chain cleavage P450, 3β-hydroxysteroid-dehydrogenase-2, 17-hydroxylase/17-20-lyase, aromatase, and SF1 were significantly higher in endometriotic tissues. PGE2 induced the expression of all steroidogenic genes; production of progesterone, estrone, and estradiol; and StAR promoter activity in endometriotic cells. Overexpression of SF1 induced, whereas COUP-TFII or WT1 suppressed, StAR promoter activity. PGE2 induced coordinate binding of SF1 to StAR and aromatase promoters but decreased COUP-TFII binding in endometriotic cells. COUP-TFII or WT1 binding to both promoters was significantly higher in endometrial compared with endometriotic cells. Conclusion: Endometriotic cells contain the full complement of steroidogenic genes for de novo synthesis of estradiol from cholesterol, which is stimulated by PGE2 via enhanced binding of SF1 to promoters of StAR and aromatase genes in a synchronous fashion.

Notch signalling regulates steroidogenesis in mouse ovarian granulosa cells

2019 ◽  
Vol 31 (6) ◽  
pp. 1091 ◽  
Author(s):  
Yishu Wang ◽  
Enhang Lu ◽  
Riqiang Bao ◽  
Ping Xu ◽  
Fen Feng ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Granulosa Cells ◽  
Notch Signalling ◽  
Side Chain ◽  
Notch Signalling Pathway ◽  
Steroidogenic Factor 1 ◽  
Ovarian Granulosa Cells ◽  
Chain Cleavage ◽  
Cleavage Enzyme ◽  
Stimulation Of

The Notch signalling pathway in the mammalian ovary regulates granulosa cell proliferation. However, the effects of Notch signalling on steroidogenesis are unclear. In this study we cultured mouse ovarian granulosa cells from preantral follicles invitro and observed the effect of Notch signalling on steroidogenesis through overexpression, knockdown and inhibition of Notch signalling. Activation of Notch signalling decreased progesterone and oestrogen secretion. In contrast, inhibition of Notch signalling increased the production of progesterone and oestrogen. Expression of the genes for steroidogenic-related enzymes, including 3β-hydroxysteroid dehydrogenase, p450 cholesterol side-chain cleavage enzyme and aromatase, was repressed after stimulation of Notch signalling. The expression of upstream transcription factors, including steroidogenic factor 1 (SF1), Wilms’ tumour 1 (Wt1), GATA-binding protein 4 (Gata4) and Gata6, was also inhibited after stimulation of Notch signalling. Production of interleukin (IL)-6 was positively correlated with Notch signalling and negatively correlated with the expression of these transcription factors and enzymes. In conclusion, Notch signalling regulated progesterone and oestrogen secretion by affecting the expression of upstream transcription factors SF1, Wt1, Gata4 and Gata6, as well as downstream steroidogenic-related enzymes. IL-6, which may be regulated directly by Notch signalling, may contribute to this process. Our findings add to the understanding of the diverse functions of Notch signalling in the mammalian ovary.

scholarly journals Growth Differentiation Factor-9 Inhibits 3′5′-Adenosine Monophosphate-Stimulated Steroidogenesis in Human Granulosa and Theca Cells

2002 ◽  
Vol 87 (6) ◽  
pp. 2849-2856 ◽  
Author(s):  
Noriko Yamamoto ◽  
Lane K. Christenson ◽  
Jan M. McAllister ◽  
Jerome F. Strauss
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Side Chain ◽  
Rt Pcr ◽  
Thecal Cell ◽  
Side Chain Cleavage ◽  
P450 Aromatase ◽  
Chain Cleavage ◽  
Thecal Cells ◽  
Growth Differentiation Factor 9

Growth differentiation factor-9 (GDF-9), a member of the transforming growth factor superfamily, modulates the development and function of granulosa and theca cells. Targeted deletion of GDF-9 in the mouse revealed that GDF-9 was essential for the establishment of the thecal cell layer during early folliculogenesis. During later stages of follicular development, the roles of GDF-9 are less well understood, but it has been postulated that oocyte-derived GDF-9 may prevent premature luteinization of follicular cells, based on its ability to modulate steroidogenesis by rodent ovarian cells. In the rodent, GDF-9 is expressed solely by the oocyte from the early primary follicular stage through ovulation. Recent studies in the rhesus monkey demonstrated that granulosa cells express GDF-9, suggesting a broader role for this protein in ovarian function in primates. We examined the effect of recombinant GDF-9 on proliferating human granulosa and thecal cell steroidogenesis and the expression of steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage, and P450 aromatase. We also examined granulosa cell GDF-9 expression by quantitative RT-PCR and by Western analysis. GDF-9 inhibited 8-Br-cAMP-stimulated granulosa progesterone synthesis by approximately 40%, but did not affect basal progesterone production. Concordant with reduced steroid production, 8-Br-cAMP-stimulated StAR protein expression was reduced approximately 40% in granulosa cells, as were expression of StAR mRNA and StAR promoter activity. Additionally, GDF-9 inhibited 8-Br-cAMP-stimulated expression of P450 side-chain cleavage and P450 aromatase. Human granulosa cells expressed GDF-9, as determined by RT-PCR and Western analysis. Treatment of human thecal cells with GDF-9 blocked forskolin-stimulated progesterone, 17α-hydroxyprogesterone, and dehydroepiandrosterone synthesis. Thecal cells exhibited greater sensitivity to GDF-9, suggesting that this cell may be a primary target of GDF-9. Moreover, GDF-9 increased thecal cell numbers during culture, but had no effect on granulosa cell growth. Our findings implicate GDF-9 in the modulation of follicular steroidogenesis, especially theca cell function. Because GDF-9 mRNA and protein are detectable in granulosa-lutein cells after the LH surge, the concept of GDF-9 as a solely oocyte-derived luteinization inhibitor needs to be reevaluated.

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