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At least 811 records · Page 45Linked to original sources
PubMed2004

Corticotropin-releasing hormone directly stimulates cortisol and the cortisol biosynthetic pathway in human fetal adrenal cells.

Near term the human fetal adrenals (HFAs) initiate production of cortisol, which promotes organ maturation and acts to increase placental CRH biosynthesis. The objective of the present study was to determine whether CRH directly stimulates both cortisol production and expression of the steroidogenic enzymes in HFA-definitive zone cells. CRH stimulated the production of cortisol in a time- and dose-dependent manner, with an effective concentration of as low as 0.01 nm. In real-time RT-PCR experiments, CRH treatment increased the mRNA levels of steroidogenic acute regulatory protein and each of the enzymes needed to produce cortisol. CRH induced 3beta-hydroxysteroid dehydrogenase type II (HSD3B2) by 34-fold, 21-hydroxylase (CYP21) by 55-fold, and 11beta-hydroxylase by 41-fold. Induction of steroidogenic acute regulatory protein, cholesterol side chain cleavage (CYP11A), and 17alpha-hydroxylase (CYP17) mRNA by CRH was 6-, 4-, and 6-fold, respectively. We also demonstrated that submaximal concentrations of CRH (30 pm) and ACTH (30 pm) that are seen in fetal circulation were additive on cortisol biosynthesis and 3beta-hydroxysteroid dehydrogenase type II mRNA induction. We suggest that CRH may play an important role in the late gestational rise in cortisol secretion from the HFAs, which may serve to augment placental CRH production and therefore participate in the endocrine cascade that is involved in fetal organ maturation and potentially in the timing of human parturition.

3-Hydroxysteroid Dehydrogenases↗
PubMed1990

Human fetal adrenal definitive and fetal zone metabolism of pregnenolone and corticosterone: alternate biosynthetic pathways and absence of detectable aldosterone synthesis.

In the rhesus monkey and ovine fetus in utero, aldosterone concentrations do not rise in response to surgical stress, ACTH, or angiotensin-II, all of which are secretagogues for this mineralocorticoid in the adult. To assess the mechanism of this phenomenon in the human fetus, metabolism of pregnenolone and corticosterone by second trimester human fetal adrenal definitive zone and fetal zone tissue was studied. After incubation of fresh tissue with trace amounts of [3H]pregnenolone or [3H]corticosterone, the products of metabolism were separated using high performance liquid chromatography and quantified. The delta 5-3 beta-hydroxysteroids 17-hydroxypregnenolone and dehydroepiandrosterone and their sulfates comprised 85-90% of metabolized pregnenolone. In the fetal zone, cortisol was the predominant secreted delta 4-3-ketosteroid, accounting for 6-8% of the metabolized pregnenolone. In the definitive zone, progesterone and corticosterone were the predominant secreted delta 4-3-ketosteroids, each accounting for about 2% of the metabolized pregnenolone. 11-Dehydrocorticosterone and sulfates were the only metabolites detected after incubation of fetal adrenal tissue with corticosterone. 11-Dehydrocorticosterone accounted for more than 80% of the metabolized corticosterone in the definitive zone and 50% in the fetal zone. Incubations with secretagogues or antioxidants (10 nmol/L ACTH, 10 nmol/L angiotensin-II, 21 mmol/L potassium, 100 mmol/L dimethylsulfoxide, 5 mumol/L metyrapone, or 100 mumol/L butylated hydroxyanisole) did not change the pattern or extent of precursor metabolism. No aldosterone, 18-hydroxycorticosterone, or 18-hydroxydeoxycorticosterone was detected in baseline or stimulated incubations of human fetal tissue. In contrast, adult human zona glomerulosa metabolized corticosterone to aldosterone, 18-hydroxycorticosterone, and 11-dehydrocorticosterone under similar conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed2000

Spectrin tethers and mesh in the biosynthetic pathway.

The paradox of how the Golgi and other organelles can sort a continuous flux of protein and lipid but maintain temporal and morphological stability remains unresolved. Recent discoveries highlight a role for the cytoskeleton in guiding the structure and dynamics of organelles. Perhaps one of the more striking, albeit less expected, of these discoveries is the recognition that a spectrin skeleton associates with many organelles and contributes to the maintenance of Golgi structure and the efficiency of protein trafficking in the early secretory pathway. Spectrin interacts directly with phosphoinositides and with membrane proteins. The small GTPase ARF, a key player in Golgi dynamics, regulates the assembly of the Golgi spectrin skeleton through its ability to control phosphoinositide levels in Golgi membranes, whereas adapter molecules such as ankyrin link spectrin to other membrane proteins. Direct interactions of spectrin with actin and centractin (ARP1) provide a link to dynein, myosin and presumably other motors involved with intracellular transport. Building on the recognized ability of spectrin to organize macromolecular complexes of membrane and cytosolic proteins into a multifaceted scaffold linked to filamentous structural elements (termed linked mosaics), recent evidence supports a similar role for spectrin in organelle function and the secretory pathway. Two working models accommodate much of the available data: the Golgi mesh hypothesis and the spectrin ankyrin adapter protein tethering system (SAATS) hypothesis.

Animals↗
PubMed1993

Defective acidification of the biosynthetic pathway in cystic fibrosis.

Cystic fibrosis is associated with defective epithelial sodium chloride and fluid secretion in epithelia. In addition, there is widespread reductions in sialylation of secreted proteins and increases in the sulfation and fucosylation of mucus glycoproteins. The major morbidity in the disease is due to the colonization of respiratory epithelia by Pseudomonas. The cystic fibrosis gene (CFTR) is a cyclic AMP activated Cl channel, which when mutated is retained in the endoplasmic reticulum. We postulate that this Cl channel is responsible for effective acidification of the Golgi. In CF cells, we demonstrate the Golgi pH is higher than in normal cells and suggest that the abnormalities in glycoprotein biosynthesis is due to changes in the kinetics of sialyl transferase, a pH sensitive enzyme. Defects in sialylation also result in decreased sialylation of glycolipids and asialogangliosides are potential Pseudomonas receptors.

Animals↗
PubMed2002

High-Yield Method for Isolation and Culture of Endothelial Cells from Rat Coronary Blood Vessels Suitable for Analysis of Intracellular Calcium and Nitric Oxide Biosynthetic Pathways.

We describe here a method for isolating endothelial cells from rat heart blood vessels by means of coronary microperfusion with collagenase. This methods makes it possible to obtain high amounts of endothelial cells in culture which retain the functional properties of their in vivo counterparts, including the ability to uptake fluorescently-labeled acetylated low-density lipoproteins and to respond to vasoactive agents by modulating intracellular calcium and by upregulating intrinsic nitric oxide generation. The main advantages of our technique are: (i) good reproducibility, (ii) accurate sterility that can be maintained throughout the isolation procedure and (iii) high yield of pure endothelial cells, mainly due to microperfusion and temperature-controlled incubation with collagenase which allow an optimal distribution of this enzyme within the coronary vascular bed.

Journal Article↗
PubMed2003

Effects of vinclozolin administration on sperm production and testosterone biosynthetic pathway in adult male rat.

The effect of vinclozolin (VCZ), used as a fungicide and known to have anti-androgenic effects on spermatogenesis and gene expression in the male rat testis was investigated. In Experiment 1, VCZ (100 mg/kg/day) or flutamide (FM, 25 mg/kg/day) was orally administered to male Holzman rats for six days. 8 days after the last administration (D8), a drastic increase in intratesticular testosterone was detected in FM (4.2-fold over control) but not in VCZ treated animals, whereas on D36 post-administration, both groups showed similar levels. Significant decreases in daily sperm production were seen in both VCZ and FM-treated rats on D36. Semiquantitative RT-PCR analysis with testicular and pituitary mRNAs on D8 revealed that LHbeta and FSHbeta mRNAs were increased in the pituitary by VCZ, as well as by FM. Among the four testicular steroidogenic enzyme genes, cytochrome P450 side chain cleavage (P450scc) and cytochrome P450 17alpha/C(17-20) lyase (P450c17) mRNAs were significantly increased, whereas 17beta-hydroxysteroid dehydrogenase type III (17betaHSD) mRNA was not changed. A significant increase in 3beta-hydroxysteroid dehydrogenase type I (3betaHSD) and a decrease in androgen receptor (AR) mRNA were observed only in FM treated rats. Immunohistochemistry demonstrated intense staining of P450scc in the interstitial cells of VCZ-treated testis on D8. In Experiment 2, hormone levels were measured at 1, 3, 6, 12 and 24 hours after VCZ (100 mg/kg) administration to Sprague-Dawley rats. Serum LH level remained constant for the first 3 hours and started to increase at 6 hrs. In contrast, serum and intratesticular testosterone levels increased 2-fold at 1 hr and maintained the level until 24 hrs. P450c17 mRNA level was 2-fold increased at all periods, whereas no obvious changes were detected in the other steroidogenic enzyme genes. Although not statistically significant, AR mRNA level increased 2-fold, 3 hrs after VCZ administration. These results indicate that VCZ affects the pituitary in a similar manner as FM, but functions differently on testicular gene expression.

Androgen Antagonists↗
PubMed2004

Biosynthetic pathway for the C45 polyprenol, solanesol, in tobacco.

Feeding experiments were independently performed with [1-13C]deoxy-D-xylulose triacetate and (RS)-[2-13C]mevalonolactone in the tobacco plant. The labeling pattern for solanesol was elucidated to reveal that the isoprene moiety of solanesol would be derived from deoxy-xylulose. The result strongly suggests that tobacco solanesol is biosynthesized via the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway.

Butadienes↗
PubMed1990

Production of 21-deoxyaldosterone by rat adrenal tissue in vitro: evidence for an alternative biosynthetic pathway of aldosterone.

Quartered rat adrenal glands transformed labelled 21-deoxyaldosterone into aldosterone in vitro. 21-deoxyaldosterone was released from the quartered rat adrenals in vitro in amounts 10 times lower than those of aldosterone and 18-hydroxycorticosterone. The production of all three steroids was qualitatively dependent on the same regulatory elements (electrolytes, ACTH, exogenous precursors, zonal specificity). However, quantitative differences could be observed. The results support a role for 21-deoxyaldosterone as a facultative precursor of aldosterone and indicate that the regulation of its production shows similarities to that of aldosterone.

18-Hydroxycorticosterone↗
PubMedDate not supplied

Sertoli cell conditioned media modulate the androgen biosynthetic pathways in rat Leydig cell primary cultures.

Increasing evidence suggests the presence of local modulators that contribute to testicular function regulation in rats. The seminiferous tubules and Sertoli cell factors influence the steroidogenic activity of Leydig cells. Addition of Sertoli cell conditioned media to primary cultures of adult rat Leydig cells produces in a dose-dependent manner an inhibition of testosterone production with a concomitant decrease in the C21 delta 4-intermediates of the steroidogenic pathway, modifying the C21/C19 ratios in normal cells. The nature and mechanisms of action of this putative modulating activity are currently under study.

17-alpha-Hydroxyprogesterone↗
PubMed1993

The nucleotide sequence of genes involved in the leucine biosynthetic pathway of Clostridium pasteurianum.

A 2.2 kb SphI/ClaI fragment of the Clostridium pasteurianum chromosome has previously been cloned and shown to complement leuB401 and leuC171 mutations in Escherichia coli. The nucleotide sequence of this fragment has been determined (2327 bp) and carries three open reading frames. The products of translation of these reading frames display significant homologies with the alpha-isopropylmalate isomerase subunit (leuD) gene of Salmonella typhimurium, the beta-isopropylmalate dehydrogenase (leuB) genes of several organisms, and the dihydroxyacid dehydrase (ilvD) gene of E. coli.

3-Isopropylmalate Dehydrogenase↗
PubMedDate not supplied

[Involvement of 3-dehydroecdysteroids in the ecdysone biosynthetic pathway in Locusta migratoria, in vitro].

Prothoracic glands of the locus, Locusta migratoria, incubated in vitro converted tritiated 3-dehydrocetodiol (22,23,24,25 3H4-14 alpha-hydroxy-5 beta-cholest-7-en-3,6-dione) into ecdysteroids and 3-dehydroecdysteroids as far as the final products of the two series, ecdysone and 3-dehydroecdysone. In the two series, the different compounds are formed in the same quantities, except for 2,22-desoxy-products, the nature of which could not have been determined. Converted 3-dehydroecdysone issued from 3-dehydrocetodiol is transformed into ecdysone after several hours incubation with Locusta last instar larvae hemolymph. Till now is has been impossible to determine if the reduction of 3-dehydroecdysteroids took place into the prothoracic glands or in the incubation medium. In no case is 3-dehydrocetodiol converted into cetodiol. Conversion rates of the different compounds, either issued from cetodiol or from 3-dehydrocetodiol as precursors, are of same importance, so that a weak specificity of the hydroxylation enzymes must be considered.

Animals↗
PubMed1996

Inhibitory effect of selenium on enzymes involved in heme biosynthetic pathway in chick embryos.

Effect of different concentrations of selenium (Se) on heme biosynthesis was studied at different developmental stages of chick embryo. The first rate limiting enzyme ALA-synthase (ALA-S; E.C.2.3-1.37) activity was enhanced by selenium, while hepatic and blood ALA-dehydratase activity (ALA-d; E.C.3.2.1.24) was decreased. Hepatic and blood free-sulfhydryl (-SH) group contents were significantly decreased by Se. Further, hepatic aminolevulinic acid (ALA) and total blood porphyrin levels were enhanced and hepatic heme levels were depleted by selenium exposure. Heme biosynthesis was maximally inhibited in the E4 (4th day injected embryos) when compared to later periods.

5-Aminolevulinate Synthetase↗
PubMed1979

The biosynthetic pathway of L-ascorbic acid in Euglena gracilis Z.

D-Glucose and D-galactose were the starting materials of L-ascorbic acid biosynthesis in Euglena gracilis as evidenced by feeding experiments of unlabeled and labeled sugars, but D-glucose was the more effective precursor. The addition of various acid derivatives of D-glucose and D-galactose, with the exception of D-glucono-delta-lactone, considerably augmented L-ascorbic acid formation. D-Galacturonic acid and L-galactono-gamma-lactone showed greater effects than did D-glucurono-gamma-lactone and L-gulono-gamma-lactone. The results of isotopic dilution experiments also showed the preference for the galacto-configuration. Fed U-14C-D-glucose was transformed into labeled D-galacturonic acid to a greater extent than into labeled D-glucuronic acid, and added D-galacturonic acid only caused extensive accumulation of labeled D-galacturonic acid. These results together show that the pathway involving D-galacturonic acid and L-galactono-gamma-lactone is the major one, the one involving D-glucuronic acid L-gulono-gamma-lactone being the minor one. A likely pathway for L-ascorbic acid biosynthesis in Euglena is proposed in the Scheme, which thus involves uronic acid intermediates and configurational inversion.

Animals↗