The role of 17 beta-hydroxysteroid dehydrogenases

Mindnich, Rebekka; Möller, Gabriele; Adamski, Jerzy

doi:10.1016/j.mce.2003.12.006

Cited by 314 publications

(224 citation statements)

References 167 publications

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“…Increased production of E 2 in granulosa cells requires transformation of androstenedione (A 4 ) to estrone (E 1 ) by cytochrome P450 aromatase (CYP19A1) activity and conversion of E 1 to E 2 by 17b-hydroxysteroid dehydrogenase (HSD17B)-reducing enzyme activity (Mindnich et al 2004, Zheng et al 2008. In large antral and preovulatory follicles, granulosa cells develop the capacity to transform cholesterol into P 4 through the expression of P 4 -synthetic enzymes, including cytochrome P450 side-chain cleavage (CYP11A1), 3b-hydroxysteroid dehydrogenase (HSD3B1), and a-glutathione S-transferase (GSTA; Bao & Garverick 1998, Rabahi et al 1999, Raffalli-Mathieu et al 2007.…”

Section: Introductionmentioning

confidence: 99%

Transforming growth factor-β1 inhibits luteinization and promotes apoptosis in bovine granulosa cells

Zheng¹,

Boerboom²,

Carrière³

2009

Reproduction

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We have previously shown that TGFB1 inhibits estradiol (E 2 ) and progesterone (P 4 ) biosynthesis in FSH-stimulated bovine granulosa cells by selective inhibition of steroidogenic enzymes. The objective of this study was to assess the effects of TGFB1 on E 2 and P 4 steroidogenesis in bovine granulosa cells cultured in the absence of FSH and to measure the effects of TGFB1 on cell proliferation and apoptosis in the presence and absence of FSH. Bovine granulosa cells from 2 to 5 mm follicles were cultured in serum-free medium for 2-6 days. In the absence of FSH, the secretion of P 4 increased with time in culture (P!0.05). Addition of TGFB1 for 6 days decreased P 4 secretion and mRNA levels of the P 4 synthesis-associated genes STAR, CYP11A1, HSD3B1, and GSTA (P!0.05). In the absence of FSH, the secretion of E 2 decreased and addition of TGFB1 for 6 days partially reversed this decline and stimulated E 2 biosynthesis, CYP19A1 and HSD17B1 mRNA levels and CYP19A1 activity (P!0.05). Conversely, TGFB1 did not affect HSD17B7 expression and HSD17B-reducing activity. TGFB1 decreased the proportion of cells in the G0/G1 and SCG2/M phases in FSHstimulated and unstimulated granulosa cells (P!0.05). Furthermore, in the presence or absence of FSH, TGFB1 increased the proportion of cells in apoptosis measured by propidium iodide staining and flow cytometry and confirmed by increased levels of cleaved caspase-3 (P!0.05). Our results therefore indicate that TGFB1 inhibits luteinization in cultured bovine granulosa cells while maintaining an estrogenic phenotype, and this effect was associated with increased apoptosis.

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Section: Introductionmentioning

confidence: 99%

Transforming growth factor-β1 inhibits luteinization and promotes apoptosis in bovine granulosa cells

Zheng¹,

Boerboom²,

Carrière³

2009

Reproduction

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“…In ruminants and humans, gonadotropin stimulation of E 2 requires luteinizing hormone (LH) stimulation of theca cells to produce androgens, mostly as androstenedione (A 4 ), and follicle-stimulating hormone (FSH)-mediated conversion of theca-derived A 4 to E 2 in granulosa cells (Fortune 1986, Hillier et al 1994. A 4 is converted to estrone (E 1 ) by cytochrome P450 aromatase (CYP19A1) and then into E 2 by 17b-hydroxysteroid dehydrogenase (HSD17B) reducing enzymes (Hillier et al 1994, Mindnich et al 2004. Granulosa cells also produce P 4 , which is necessary for the induction of ovulation (Drummond 2006).…”

Section: Introductionmentioning

confidence: 99%

Role of transforming growth factor-β1 in gene expression and activity of estradiol and progesterone-generating enzymes in FSH-stimulated bovine granulosa cells

Zheng

Price²,

Tremblay³

et al. 2008

Reproduction

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Survival and inhibitory factors regulate steroidogenesis and determine the fate of developing follicles. The objective of this study was to determine the role of transforming growth factor-b1 (TGFB1) in the regulation of estradiol-17b (E 2 ) and progesterone (P 4 ) secretion in FSHstimulated bovine granulosa cells. Granulosa cells were obtained from 2 to 5 mm follicles and cultured in serum-free medium. FSH dose (1 and 10 ng/ml for 6 days) and time in culture (2, 4, and 6 days with 1 ng/ml FSH) increased E 2 secretion and mRNA expression of E 2 -related enzymes cytochrome P450 aromatase (CYP19A1) and 17b-hydroxysteroid dehydrogenase type 1 (HSD17B1), but not HSD17B7. TGFB1 in the presence of FSH (1 ng/ml) inhibited E 2 secretion, and decreased mRNA expression of FSH receptor (FSHR), CYP19A1, and HSD17B1, but not HSD17B7. FSH dose did not affect P 4 secretion and mRNA expression of 3b-hydroxysteroid dehydrogenase (HSD3B) and a-glutathione S-transferase (GSTA), but inhibited the amount of steroidogenic acute regulatory protein (STAR) mRNA. Conversely, P 4 and mRNA expression of STAR, cytochrome P450 side-chain cleavage (CYP11A1), HSD3B, and GSTA increased with time in culture. TGFB1 inhibited P 4 secretion and decreased mRNA expression of STAR, CYP11A1, HSD3B, and GSTA. TGFB1 modified the formation of granulosa cell clumps and reduced total cell protein. Finally, TGFB1 decreased conversion of androgens to E 2 , but did not decrease the conversion of estrone (E 1 ) to E 2 and pregnenolone to P 4 . Overall, these results indicate that TGFB1 counteracts stimulation of E 2 and P 4 synthesis in granulosa cells by inhibiting key enzymes involved in the conversion of androgens to E 2 and cholesterol to P 4 without shutting down HSD17B reducing activity and HSD3B activity.

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“…Higher animals cannot synthetize them and thus require them as vitamins. The majority of vitamins are enzyme cofactors or precursors of them (Michal, 1999). Figure 3 exemplifies structures.…”

Section: Vitamins and Enzyme Cofactorsmentioning

confidence: 99%

“…Only Archaea and Bacteria can synthetize it (Michal, 1999;Asensi-Fabado and Munné-Bosch, 2010). Other important vitamins include thiamine (3.7), vitamin B 1 , which is important for oxidative decarboxylation and also can act as antioxidant (Michal, 1999;Jung and Kim, 2003); carboxylation reactions depend on biotin (3.8); pyridoxal phosphate (3.9) is involved in various modifications at the carbon atom 2 of amino acids (Michal, 1999;Ferrier and Harvey, 2014). Ascorbic acid (3.10), also known as vitamin C, confers protection against oxidative stress by acting as antioxidant.…”

Section: Vitamins and Enzyme Cofactorsmentioning

confidence: 99%

Low-molecular-weight metabolite systems chemistry

Hadaček

Bachmann

2015

Front. Environ. Sci.

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Low-molecular-weight metabolites (LMWMs) comprise primary or central and a plethora of intermediary or secondary metabolites, all of which are characterized by a molecular weight below 900 Dalton. The latter are especially prominent in sessile higher organisms, such as plants, corals, sponges and fungi, but are produced by all types of microbial organisms too. Common to all of these carbon molecules are oxygen, nitrogen and, to a lesser extent, sulfur, as heteroatoms. The latter can contribute as electron donators or acceptors to cellular redox chemistry and define the potential of the molecule to enter charge-transfer complexes. Furthermore, they allow LMWMs to serve as organic ligands in coordination complexes with various inorganic metals as central atoms. Especially the transition metals Fe, Cu, and Mn can catalyze one electron reduction of molecular oxygen, which results in formation of free radical species and reactive follow-up reaction products. As antioxidants LMWMs can scavenge free radicals. Depending on the chemical environment, the same LMWMs can act as pro-oxidants by reducing molecular oxygen. The cellular regulation of redox homeostasis, a balance between oxidation and reduction, is still far from being understood. Charge-transfer and coordination complex formation with metals shapes LMWMs into gel-like matrices in the cytosol. The quasi-polymer structure is lost usually during the isolation procedure. In the gel state, LMWMs possess semiconductor properties. Also proteins and membranes are semiconductors. Together they can represent biotransistor components that can be part of a chemoelectrical signaling system that coordinates systems chemistry by initiating cell differentiation or tissue homeostasis, the activated and the resting cell state, when it is required. This concept is not new and dates back to Albert Szent-Györgyi.

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The role of 17 beta-hydroxysteroid dehydrogenases

Cited by 314 publications

References 167 publications

Transforming growth factor-β1 inhibits luteinization and promotes apoptosis in bovine granulosa cells

Transforming growth factor-β1 inhibits luteinization and promotes apoptosis in bovine granulosa cells

Role of transforming growth factor-β1 in gene expression and activity of estradiol and progesterone-generating enzymes in FSH-stimulated bovine granulosa cells

Low-molecular-weight metabolite systems chemistry

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