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.

Rat cholesterol side-chain cleavage enzyme (P-450scc): use of a cDNA probe to study the hormonal regulation of P-450scc mRNA levels in ovarian granulosa cells

Gene ◽  
1987 ◽  
Vol 57 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Kelly M. McMasters ◽  
Leon A. Dickson ◽  
Rebecca V. Shamy ◽  
Kathleen Robischon ◽  
Gordon J. Macdonald ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Hormonal Regulation ◽  
Cdna Probe ◽  
Side Chain ◽  
Mrna Levels ◽  
Side Chain Cleavage ◽  
Ovarian Granulosa Cells ◽  
Chain Cleavage ◽  
Cleavage Enzyme

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.

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 Combined Loss of the GATA4 and GATA6 Transcription Factors in Male Mice Disrupts Testicular Development and Confers Adrenal-Like Function in the Testes

Endocrinology ◽  
2015 ◽  
Vol 156 (5) ◽  
pp. 1873-1886 ◽  
Author(s):  
Maria B. Padua ◽  
Tianyu Jiang ◽  
Deborah A. Morse ◽  
Shawna C. Fox ◽  
Heather M. Hatch ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Double Mutant ◽  
Immunohistochemical Analysis ◽  
Side Chain ◽  
Testicular Development ◽  
Down Regulation ◽  
Chain Cleavage ◽  
Genes Encoding ◽  
Cleavage Enzyme ◽  
Steroidogenic Genes

The roles of the GATA4 and GATA6 transcription factors in testis development were examined by simultaneously ablating Gata4 and Gata6 with Sf1Cre (Nr5a1Cre). The deletion of both genes resulted in a striking testicular phenotype. Embryonic Sf1Cre; Gata4flox/flox Gata6flox/flox (conditional double mutant) testes were smaller than control organs and contained irregular testis cords and fewer gonocytes. Gene expression analysis revealed significant down-regulation of Dmrt1 and Mvh. Surprisingly, Amh expression was strongly up-regulated and remained high beyond postnatal day 7, when it is normally extinguished. Neither DMRT1 nor GATA1 was detected in the Sertoli cells of the mutant postnatal testes. Furthermore, the expression of the steroidogenic genes Star, Cyp11a1, Hsd3b1, and Hsd17b3 was low throughout embryogenesis. Immunohistochemical analysis revealed a prominent reduction in cytochrome P450 side-chain cleavage enzyme (CYP11A1)- and 3β-hydroxysteroid dehydrogenase-positive (3βHSD) cells, with few 17α-hydroxylase/17,20 lyase-positive (CYP17A1) cells present. In contrast, in postnatal Sf1Cre; Gata4flox/flox Gata6flox/flox testes, the expression of the steroidogenic markers Star, Cyp11a1, and Hsd3b6 was increased, but a dramatic down-regulation of Hsd17b3, which is required for testosterone synthesis, was observed. The genes encoding adrenal enzymes Cyp21a1, Cyp11b1, Cyp11b2, and Mcr2 were strongly up-regulated, and clusters containing numerous CYP21A2-positive cells were localized in the interstitium. These data suggest a lack of testis functionality, with a loss of normal steroidogenic testis function, concomitant with an expansion of the adrenal-like cell population in postnatal conditional double mutant testes. Sf1Cre; Gata4flox/flox Gata6flox/flox animals of both sexes lack adrenal glands; however, despite this deficiency, males are viable in contrast to the females of the same genotype, which die shortly after birth.

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