Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tremella mesenterica (TM), a yellow jelly mushroom, has been traditionally used as tonic food to improve body condition in Chinese society for a long time. We have previously demonstrated that TM reduced in vitro hCG-treated steroidogenesis in MA-10 mouse Leydig tumor cells without any toxicity effect. In the present study, the mechanism how TM suppressed hCG-treated steroidogenesis in MA-10 cells was investigated. MA-10 cells were treated with vehicle, human chorionic gonadotropin (hCG, 50 ng/ml), or different reagents with or without TM to clarify the effects. TM significantly suppressed progesterone production with the presences of forskolin (10 and 100 microM) or dbcAMP (0.5 and 1mM), respectively, in MA-10 cells (p<0.05), which indicated that TM suppressed steroidogenesis after PKA activation along the signal pathway. Beyond our expectation, TM induced the expression of steroidogenic acute regulatory (StAR) protein with or without hCG treatments. However, TM profoundly decreased P450 side chain cleavage (P450scc) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) enzyme activities without any influences on the expression of both enzymes. These inhibitions on steroidogenic enzyme activities might counteract the stimulation of StAR protein expression. In conclusion, results suggest that TM suppressed hCG-treated steroidogenesis in MA-10 cells by inhibiting PKA signal pathway and steroidogenic enzyme activities.
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PMID:The regulatory mechanism of Tremella mesenterica on steroidogenesis in MA-10 mouse Leydig tumor cells. 1650 11

Di-n-butyl phthalate (DBP) is one of the most dominant phthalate esters and is widely distributed environmental contaminant. Although previous studies have demonstrated that DBP led to a variety of male reproductive abnormalities similar to those caused by androgen receptor antagonists, DBP and its active metabolite, mono-butyl phthalate (MBP), have been demonstrated no affinity for the androgen receptor, but rather exert anti-androgenic effect by altering testosterone biosynthesis. Furthermore, all these results were obtained from very high administrations of DBP or MBP. The purpose of this study was to determine the onset and the site of action of relatively low concentration of MBP on steroidogenesis in vitro. The mouse Leydig tumor cells (MLTC-1) was employed as a cellular model to investigate the effect of MBP on steroidogenesis. Various concentrations of MBP (1, 10, 100 and 1000nmol/l) and its solvent dimethyl sulfoxide (DMSO) were added to the medium for 24h followed by stimulation of some compounds such as human chorionic gonadotrophin (hCG), cholera toxin (CT), forskolin, cAMP analog 8-Br-cAMP, 22(R)-hydroxycholesterol (22R-HC) and pregnenolone. Progesterone in the medium and amounts of intracellular cAMP were measured by RIA. Expression of steroidogenic acute regulatory protein (StAR) was monitored by real-time PCR and Western blotting. The results revealed that the increases of progesterone production in the presence of hCG, CT, forskolin and 8-Br-cAMP were augmented by MBP. In contrast, the levels of intracellular cAMP exhibited no statistical significance when MLTC-1 cells were treated as above. These results implied that the site in the steroid biosynthesis pathway affected by MBP occurs after PKA activation in MLTC-1 cells. Moreover, supplementing the medium with 22R-HC and pregnenolone as progesterone precursors for P450 side chain cleavage enzyme (P450scc) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD), respectively, resulted in no rise in progesterone production, making clear that MBP did not influence the P450scc and 3beta-HSD but on the rate-limiting step, cholesterol transportation into mitochondria. In fact, the above results were confirmed by the upgraded StAR expression in MBP-treated cells. These data support that MBP promotes steroid hormone production by facilitating StAR expression in MLTC-1 cells.
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PMID:Low concentrations mono-butyl phthalate stimulates steroidogenesis by facilitating steroidogenic acute regulatory protein expression in mouse Leydig tumor cells (MLTC-1). 1699 44

Calcitriol exerts a diverse range of biological actions including the control of growth and cell differentiation, modulation of hormone secretion, and regulation of reproductive function. The placenta synthesizes calcitriol through the expression of CYP27B1, but little is known about local actions of this hormone in the fetoplacental unit. The objective of this study was to investigate the effects of calcitriol upon progesterone (P(4)) and estradiol (E(2)) secretion in trophoblasts cultured from term human placenta. Cells were incubated in the presence of calcitriol for 18 h and pregnenolone or androstenedione were subsequently added as substrates for the 3beta-hydroxysteroid dehydrogenase (3beta-HSD) or P450-aromatase (CYP19), respectively. Calcitriol stimulated in a dose-dependent manner E(2) and P(4) secretion. The use of a selective inhibitor of PKA prevented the effects of calcitriol upon E(2) secretion, but not on P(4). These results show that calcitriol is a physiological regulator of placental E(2) and P(4) production and suggest a novel role for calcitriol upon placental steroidogenesis.
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PMID:Estradiol and progesterone synthesis in human placenta is stimulated by calcitriol. 1725 26

Di-n-butyl phthalate (DBP) and its active metabolite, monobutyl phthalate (MBP), display no binding affinity for the androgen receptor, yet exert antiandrogenic effects by altering steroid biosynthesis. However, the mechanisms underlying this observed effect are not known. The purpose of this study was to determine the site of MBP action on steroidogenesis in vitro using mouse Leydig tumor cells (MLTC-1). Various concentrations of MBP (0, 50, 100, 200, 400, or 800 micromol/L) were added to the medium for 24 h followed by stimulation with some compounds such as human chorionic gonadotrophin (hCG), cholera toxin (CT), cAMP analog 8-Br-cAMP, 22(R)-hydroxycholesterol (22R-HC), and pregnenolone. Data showed that MBP inhibited the increases in progesterone production induced by hCG and CT. In contrast, the levels of intracellular cAMP remained unaltered. In addition, 8-Br-cAMP-stimulated progesterone production was also suppressed by MBP. These results suggested that the site in the steroid biosynthesis pathway affected by MBP occurs downstream of PKA activation in MLTC-1 cells. Moreover, incubation with 22R-HC and pregnenolone as progesterone precursors for P-450 side-chain cleavage enzyme (P450scc) and 3beta-hydroxysteroid dehydrogenase (3betaHSD) respectively resulted in no marked change in progesterone production, indicating that MBP did not influence P450scc and 3betaHSD but did exert an effect on cholesterol transportation into mitochondria, the rate-limiting step. These results were supported by the downregulated StAR expression seen with MBP administration, as StAR is a key factor in this process. Data indicate that MBP interfered with steroid hormone production by affecting StAR expression in MLTC-1 cells.
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PMID:Monobutyl phthalate inhibits steroidogenesis by downregulating steroidogenic acute regulatory protein expression in mouse Leydig tumor cells (MLTC-1). 1747 10

The expression of main extracellular matrix (ECM) and their integrins were studied in the adult rat adrenal gland. Collagen I, IV (CI, CIV), laminin (LN) and fibronectin (FN) expression was observed surrounding each glomerulosa cell and as long fibrils between the cords of fasciculata cells. In the medulla, FN was present around chromaffin cells or bordering blood vessels. Integrin alpha2, alpha3 and alpha5 were present mainly in the cortex, while alpha1 was present in the medulla. In culture, all ECM favoured proliferation of both glomerulosa and fasciculata cells, while protein synthesis was lower on FN and LN in glomerulosa cells. CIV promoted ACTH-induced proliferation whereas FN favoured ACTH-induced protein synthesis in glomerulosa cells. Except for LN, ECM increased expression of 3beta-hydroxysteroid dehydrogenase and enhanced basal aldosterone, although corticosterone secretion was only enhanced by CI and CIV. In fasciculata cells, the potency of ACTH-induced cAMP production was lower on ECM, compared with plastic. Moreover, ACTH, but not ECM, activated mitogenic-activated protein kinase p38 and stress-activated protein kinases. Glomerulosa and fasciculata cells grown on CI and CIV had a polygonal morphology, while cells grown on LN appeared as clusters of small rounded cells. On FN, the glomerulosa cells exhibited polygonal morphology while fasciculata cells appeared as clusters of small rounded cells. Together, these results indicate that ECM modulates basal and ACTH-induced cell functions, with FN, CI and CIV specifically favouring steroid secretion, as opposed to LN which inhibits secretion while promoting proliferation.
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PMID:Expression of extracellular matrix proteins and integrins in rat adrenal gland: importance for ACTH-associated functions. 1753 72

The endocrine pathways controlling vertebrate spermatogenesis are well established in mammals where the pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) exclusively activate the FSH receptor (FSHR) in Sertoli cells and the LH/choriogonadotropin receptor (LHCGR) in Leydig cells, respectively. In some teleosts, however, it has been shown that Lh can cross-activate the Fshra ortholog, and that Leydig cells coexpress the Lhcgrba and Fshra paralogs, thus mediating the androgenic function of Fsh in the testis. Here, we investigated whether these proposed mechanisms are conserved in an evolutionary advanced pleuronectiform teleost, the Senegalese sole (Solea senegalensis). Transactivation assays using sole Fshra- and Lhcgrba-expressing cells and homologous single-chain recombinant gonadotropins (rFsh and rLh) showed that rFsh exclusively activated Fshra, whereas rLh stimulated both Lhcgrba and Fshra. The latter cross-activation of Fshra by rLh occurred with an EC(50) 4-fold higher than for rFsh. Both recombinant gonadotropins elicited a significant androgen release response in vitro and in vivo, which was blocked by protein kinase A (PKA) and 3beta-hydroxysteroid dehydrogenase inhibitors, suggesting that activation of steroidogenesis through the cAMP/PKA pathway is the major route for both Lh- and Fsh-stimulated androgen secretion. Combined in situ hybridization and immunocytochemistry using cell-specific molecular markers and antibodies specifically raised against sole Fshra and Lhcgrba demonstrated that both receptors are expressed in Leydig cells, whereas Sertoli cells only express Fshra. These data suggest that Fsh-mediated androgen production through the activation of cognate receptors in Leydig cells is a conserved pathway in Senegalese sole.
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PMID:Follicle-stimulating hormone and luteinizing hormone mediate the androgenic pathway in Leydig cells of an evolutionary advanced teleost. 2264 73


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