High impact information on STAR

• These data indicate that GATA-4 and C/EBPbeta are both required for FSH +/- IGF-I stimulation of the porcine steroidogenic acute regulatory protein gene promoter in homologous granulosa cell cultures [1].
• We previously demonstrated that FSH alone or in combination with IGF-I activated the porcine steroidogenic acute regulatory protein gene promoter in a concerted manner in primary cultures of granulosa cells [1].
• Concerted regulation of the porcine steroidogenic acute regulatory protein gene promoter activity by follicle-stimulating hormone and insulin-like growth factor I in granulosa cells involves GATA-4 and CCAAT/enhancer binding protein beta [1].
• Insulin and insulin-like growth factor I (IGF-I) can amplify gonadotropin-stimulated steroidogenesis by augmenting the expression of key sterol regulatory genes in ovarian cells, viz. low density lipoprotein (LDL) receptor, steroidogenic acute regulatory protein, and P450 cholesterol side-chain cleavage enzyme (CYP11A) [2].
• Together, these investigations document a significant role for insulin or IGF-I in enhancing LH-stimulated progesterone and cAMP biosynthesis and endogenous StAR message and protein accumulation and in augmenting cAMP-PKA-dependent transcriptional activation of the exogenous StAR promoter [3].

Biological context of STAR

• Surprisingly, EGF (1-50 ng/ml) did not affect FSH stimulation of a 1423-base pair StAR gene promoter-luciferase construct in transient transfection assays in porcine granulosa cells [4].
• Epidermal growth factor-mediated inhibition of follicle-stimulating hormone-stimulated StAR gene expression in porcine granulosa cells is associated with reduced histone H3 acetylation [4].
• Concerted regulation of steroidogenic acute regulatory gene expression by luteinizing hormone and insulin (or insulin-like growth factor I) in primary cultures of porcine granulosa-luteal cells [3].
• To determine the hormonal responsiveness of StAR promoter, truncated regions of the -1423 to +130 bp upstream sequence of the porcine gene were ligated into a firefly luciferase reporter plasmid [3].
• In corollary analyses of the protein kinase A (PKA) pathway, cotransfection of full-length pStAR1423/luc and a complementary DNA encoding a constitutively activated PKA catalytic subunit elevated basal and insulin (or IGF-I)-stimulated StAR promoter expression [3].

Anatomical context of STAR

• Steroidogenic acute regulatory protein (StAR) mediates cholesterol transport into the mitochondria and is essential for ovarian steroidogenesis [4].
• Recently, our laboratory developed an in vitro primary culture system of porcine granulosa-luteal cells that retain responsiveness to LH and show LH and insulin [or insulin-like growth factor (IGF-I)] synergy in stimulating StAR messenger RNA accumulation [3].
• The steroidogenic acute regulatory (StAR) protein is indispensable for maximal trophic hormone-stimulated steroidogenesis by the adrenal gland, testis, and ovary [3].
• The transfer of cholesterol from the outer to the inner mitochondrial membrane, where side-chain cleavage occurs to form pregnenolone, is a crucial event in the regulation of steroidogenesis and recently has been demonstrated to be mediated by steroidogenic acute regulatory protein (StAR) [5].
• StAR mRNA and protein as well as cytochrome P450 side-chain cleavage mRNA (P450scc) increased during the luteal phase in the corpus luteum (CL) and were absent in regressed CL [6].

Associations of STAR with chemical compounds

• Tumor necrosis factor-alpha inhibits leydig cell steroidogenesis through a decrease in steroidogenic acute regulatory protein expression [7].
• Protein kinase A agonist, 8-bromoadenosine 3',5'-cAMP (8-bromo-cAMP) (1 mM) alone elicited a 3.5-fold increase in StAR message and more than 3.7-fold increase in StAR protein expression by 48 h [5].
• In summary, P450scc and StAR message expression are coordinately amplified during the pig follicular and luteal phase, whereas LDL receptor message after an initial increase is expressed at constitutively high levels, thus indicating a differential regulation of ovarian sterol-metabolizing genes during the steroidogenic life of the follicle and CL [8].
• Dibutyryl cAMP caused time-dependent increases in StAR and P450 mRNAs over 24 h (p < 0.001), indicating the importance of the protein kinase A (PKA) pathway in their gene expression [9].
• Over 6 h, actinomycin D eliminated constitutive StAR message and reduced that of P450scc by two thirds, indicating briefer persistence of StAR [9].

Regulatory relationships of STAR

• Previous studies have demonstrated FSH stimulates StAR mRNA accumulation and gene promoter activation in granulosa cells [4].

Other interactions of STAR

• Cotransfection of primary cultures of luteinizing granulosa cells with GATA-4 or GATA-6 expression vectors increased the activity of the porcine steroidogenic acute regulatory protein gene promoter significantly but did not significantly activate the inhibin alpha gene promoter [10].
• To evaluate FSH and EGF effects on the endogenous StAR gene, chromatin immunoprecipitation assays were performed in combination with real-time polymerase chain reaction [4].
• Localization and expression of low-density lipoprotein receptor, steroidogenic acute regulatory protein, cytochrome P450 side-chain cleavage and P450 17-alpha-hydroxylase/C17-20 lyase in developing swine follicles: in situ molecular hybridization and immunocytochemical studies [11].
• Sequence variation and evaluation of inhibin alpha-subunit and steroidogenic acute regulatory protein for reproductive traits in swine [12].
• Investigation into the mechanism of action found that BMP-2 and -6 decreased cyclic adenosine monophosphate (cAMP) production (P<0.01), expression of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) protein (P<0.001) and steroidogenic acute regulatory protein (StAR) (BMP-6 only; P<0.05) [13].

Analytical, diagnostic and therapeutic context of STAR

• LH and insulin (or IGF-I) also augmented steady state StAR transcript levels, as assessed by homologous RT-PCR, and StAR protein concentrations, as evaluated by Western blotting [3].
• In vitro luteinization of granulosa cells occurred over 96 h in culture, during which P450arom mRNA was present at 1 h after cell isolation but not detectable at 6 h; and P450scc and StAR mRNAs were first detectable at 6 h and 48 h, respectively [6].

References