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Results for “Dual control”

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PubMed1986

Hormonal control of fructose 2,6-bisphosphate concentration in the HT29 human colon adenocarcinoma cell line. Alpha 2-adrenergic agonists counteract effect of vasoactive intestinal peptide.

Vasoactive intestinal peptide (VIP) was found to cause a dose-dependent decrease in fructose 2,6-bisphosphatase concomitant with an increase in cyclic AMP in cultured HT29 cancer cells from human colon. The maximum effect was a 41% decrease obtained with 10 nM-VIP, and half-maximum effect was obtained with 0.75 nM-VIP. The effect of 2.5 nM-VIP was almost totally counteracted (i.e. fructose 2,6-bisphosphate concentration was restored) by either adrenaline (1 microM) or the alpha 2-adrenergic agonist UK-14304 (1 microM); the alpha 2-agonist clonidine (1 microM) was less efficient, since the VIP effect was decreased by 72% only. The adrenaline effect was totally antagonized by 1 microM-yohimbine. It is concluded that, in the HT29 cancer cells, the fructose 2,6-bisphosphate-producing system is sensitive to variations of cyclic AMP concentration and is under the dual control of VIP and alpha 2-adrenergic receptors.

Adenocarcinoma↗

PubMed2001

Coupling of asymmetric division to polar placement of replication origin regions in Bacillus subtilis.

Entry into sporulation in Bacillus subtilis is characterized by the formation of a polar septum, which asymmetrically divides the developing cell into forespore (the smaller cell) and mother cell compartments, and by migration of replication origin regions to extreme opposite poles of the cell. Here we show that polar septation is closely correlated with movement of replication origins to the extreme poles of the cell. Replication origin regions were visualized by the use of a cassette of tandem copies of lacO that had been inserted in the chromosome near the origin of replication and decorated with green fluorescent protein-LacI. The results showed that extreme polar placement of replication origin regions is not under sporulation control and occurred in stationary phase under conditions under which entry into sporulation was prevented. On the other hand, the formation of a polar septum, which is under sporulation control, was almost invariably associated with the presence of a replication origin region in the forespore. Moreover, cells in which the polar placement of origin regions was perturbed by deletion of the gene (smc) for the structural maintenance of chromosomes (SMC) protein were impaired in polar division. A small proportion ( approximately 1%) of the mutant cells were able to undergo asymmetric division, but the forespore compartment of these exceptional cells was generally observed to contain a replication origin region. Immunofluorescence microscopy experiments indicated that the block in polar division caused by the absence of SMC occurred at or prior to the step of bipolar Z-ring formation by the cell division protein FtsZ. A model is discussed in which polar division is under the dual control of sporulation and an event associated with the placement of a replication origin at the cell pole.

Bacillus subtilis↗

PubMed1988

Sympathetic control of antral and pyloric electrical activity in the rabbit.

The effects of section and stimulation of the sympathetic nerve trunk on gastric motility were investigated in conscious and decorticate rabbits. In conscious animals after section of the abdominal splanchnic nerve, rhythm of antral and pyloric bursts was enhanced, becoming more regular, and the period of arrest of the rhythmic bursts, which was usually observed at the end of inflation of the antrum in intact rabbits, was shortened to 33.6 +/- 4.0 s from 112.2 +/- 14.6 s observed before the sympathetic nerve transection. Adrenergic agonists, phenylephrine (100 micrograms/kg), clonidine (5 micrograms/kg) and salbutamol (1 mg/kg) inhibited antral and pyloric activity. In decorticate rabbits the major effect of stimulation of the peripheral or the central end of the thoracic sympathetic trunk was inhibition; this was seen both with the spontaneous and vagally induced e.m.g. activity of the antrum and pylorus. Inhibition induced by stimulation of sympathetic efferents was abolished by beta-blocking agents and that induced by stimulation of the sympathetic afferents disappeared after alpha-adrenergic block. Significance of a dual control of the gastric motility by the sympathetic nerve was discussed.

Afferent Pathways↗

PubMed1983

Avian renal portal valve: a reexamination of its innervation.

The renal portal circulation of the avian kidney contains a unique smooth muscle valve that can direct blood flow from the posterior extremities to the central circulation or through the kidney. The neural control of the valve and adjacent venous tissue from Rhode Island Red roosters was characterized by measuring the isometric force developed following transmural nerve stimulation (TNS). During TNS, the valve relaxed while the iliac vein contracted. In the valve, a poststimulus contraction followed the relaxation. Propranolol and guanethidine abolished the TNS-induced relaxation of the valve, leaving a contraction that was increased by physostigmine and partially blocked by atropine or prazosin. In contrast, the TNS-induced contraction of the vein was blocked by guanethidine or prazosin. Measurement of choline acetyltransferase activity and norepinephrine content confirms that the valve is densely innervated with both cholinergic and adrenergic nerves. Thus the vein shows a predominantly adrenergic contractile response typical of most vascular smooth muscle, but the valve demonstrates a dual control, i.e., adrenergic nerves producing relaxation and cholinergic nerves causing contraction. Knowledge of the nature of neuronal control of the valve should aid in the design of experiments to determine its functional role.

Animals↗

PubMed2006

Rem, a new transcriptional activator of motility and chemotaxis in Sinorhizobium meliloti.

The expression of 51 known genes clustered in the flagellar regulon of Sinorhizobium meliloti is organized as a three-class hierarchy: class IA comprises the master regulatory genes, visN and visR; class II, controlled by VisNR, comprises flagellar assembly and motility genes; and class III comprises flagellin and chemotaxis genes requiring class II for expression. The expression of visN-visR is constitutive throughout growth, whereas that of class II and class III genes is limited to exponential growth. A new OmpR-like, 25-kDa transcription factor, Rem, whose synthesis is confined to exponential growth, was shown to positively control swimming motility. No phosphorylation of the receiver domain of Rem was required for its activity. Gene expression in tester strains with known deficiencies placed the rem gene (class IB) below visN-visR (class IA) and above class II genes in the regulatory cascade. Footprinting analysis demonstrated that the Rem protein binds to class II gene promoters as well as to its own promoter, indicating that this protein is autoregulatory. An alignment of the Rem-protected DNA sequences revealed a conserved binding motif of imperfect tandem repeats overlapping a predicted -35 promoter box by 3 bp. This new promoter was confirmed by mapping the transcription start site of a typical class II gene, flgB, 5 nucleotides downstream of the -10 promoter box. The transcription of rem is under dual control of an upstream (Rem-activated) class II-type promoter and a downstream (VisNR-activated) sigma70-like promoter. The central role of Rem as the growth-dependent transcriptional activator intermediate between the master regulator, VisNR, and the flagellar and motility genes is a new distinguishing feature of the S. meliloti regulatory cascade.

Amino Acid Sequence↗

PubMed1965

PROPERTIES OF PHOSPHOFRUCTOKINASE FROM RAT LIVER AND THEIR RELATION TO THE CONTROL OF GLYCOLYSIS AND GLUCONEOGENESIS.

1. Phosphofructokinase from rat liver has been partially purified by ammonium sulphate precipitation so as to remove enzymes that interfere in one assay for phosphofructokinase. The properties of this enzyme were found to be similar to those of the same enzyme from other tissues (e.g. cardiac muscle, skeletal muscle and brain) that were previously investigated by other workers. 2. Low concentrations of ATP inhibited phosphofructokinase activity by decreasing the affinity of the enzyme for the other substrate, fructose 6-phosphate. Citrate, and other intermediates of the tricarboxylic acid cycle, also inhibited the activity of phosphofructokinase. 3. This inhibition was relieved by either AMP or fructose 1,6-diphosphate; however, higher concentrations of ATP decreased and finally removed the effect of these activators. 4. Ammonium sulphate protected the enzyme from inactivation, and increased the activity by relieving the inhibition due to ATP. The latter effect was similar to that of AMP. 5. Phosphofructokinase was found in the same cellular compartment as fructose 1,6-diphosphatase, namely the soluble cytoplasm. 6. The properties of phosphofructokinase and fructose 1,6-diphosphatase are compared and a theory is proposed that affords dual control of both enzymes in the liver. The relation of this to the control of glycolysis and gluconeogenesis is discussed.

Adenine Nucleotides↗

PubMed2006

Integrin-linked kinase, a hypoxia-responsive molecule, controls postnatal vasculogenesis by recruitment of endothelial progenitor cells to ischemic tissue.

BACKGROUND: Recruitment and adhesion of endothelial progenitor cells (EPCs) to hypoxic endothelial cells (ECs) is essential for vasculogenesis in ischemic tissue; little is known, however, about the key signals or intracellular signaling pathways involved in orchestrating the expression of adhesion molecules by ECs in response to hypoxia and how this is related to the recruitment of EPCs to the ischemic tissue. Here, we report that endogenous integrin-linked kinase (ILK) is a novel molecule that responds to hypoxia in ECs that regulates the expression of stromal cell-derived factor-1 (SDF-1) and intercellular adhesion molecule-1 (ICAM-1) through nuclear factor-kappaB and hypoxia-inducible factor-1alpha and induces recruitment of EPCs to ischemic areas. METHODS AND RESULTS: Under hypoxia, both the endogenous amount and kinase activity of ILK were time-dependently upregulated in ECs, which was associated with increased ICAM-1 and SDF-1. This upregulation of ILK was mediated by stabilization of ILK by heat shock protein 90. ILK overexpression in normoxic ECs resulted in ICAM-1 and SDF-1 upregulation through dual control by nuclear factor-kappaB and hypoxia-inducible factor-1alpha. Blockade of ILK in hypoxic ECs significantly abrogated the expression of both molecules, which led to decreased EPC incorporation into ECs. A hindlimb ischemia model showed that ILK blockade significantly reduced EPC homing to ischemic limb and consequently led to poor neovascularization. Overexpression of ILK in the Matrigel plug significantly improved neovascularization in vivo, whereas the blockade of ILK resulted in the opposite effect. CONCLUSIONS: Endogenous ILK is a novel and physiological upstream responder of numerous intracellular molecules involved in hypoxic stress in ECs and may control the recruitment of EPCs to ischemic tissue.

Cell Adhesion↗

PubMed2003

Phagosomal oxidative activity during beta2 integrin (CR3)-mediated phagocytosis by neutrophils is triggered by a non-restricted Ca2+ signal: Ca2+ controls time not space.

The temporal and spatial relationship between particle binding to the neutrophil by beta2 integrin (CR3), the Ca2+ elevation and subsequent oxidase activation has been unclear. This is because of the difficulty in studying the time course of individual phagocytic events in individual neutrophils. Here, we have used a micromanipulation technique to present C3bi-opsonised zymosan particles to the neutrophil under observation. In this way, the moment of particle contact, pseudopod formation and internalisation has been established and cytosolic free Ca2+ and oxidation of dichlorodihydrofluorescein (DCDHF)-labelled particles determined simultaneously. Using this approach, we have found that the Ca2+ signal, which is triggered by CR3-mediated phagocytosis, can be resolved into two temporally separated components. The first Ca2+ signal occurs during beta2 integrin engagement as the phagocytic cup forms but does not trigger oxidation of the particle. The second global Ca2+ signal, which is triggered about the time of phagosomal closure, causes an abrupt activation of the oxidase. This second Ca2+ signal was not restricted to the region of the phagosome yet only triggered the oxidase activation locally in the phagosome, with no evidence of activation at other sites in the neutrophil. This points to a dual control of oxidase activation, with Ca2+ controlling the timing of oxidase activation but slower and more localised molecular events, perhaps involving oxidase assembly and phosphatidylinositol 3-phosphate generation, determining the site of oxidase activation.

Anticoagulants↗

PubMed2000

Stimulation by iodide of H(2)O(2) generation in thyroid slices from several species.

The regulation of thyroid metabolism by iodide involves numerous inhibitory effects. However, in unstimulated dog thyroid slices, a small inconstant stimulatory effect of iodide on H(2)O(2) generation is observed. The only other stimulatory effect reported with iodide is on [1-(14)C]glucose oxidation, i.e., on the pentose phosphate pathway. Because we have recently demonstrated that the pentose phosphate pathway is controlled by H(2)O(2) generation, we study here the effect of iodide on basal H(2)O(2) generation in thyroid slices from several species. Our data show that in sheep, pig, bovine, and to a lesser extent dog thyroid, iodide had a stimulatory effect on H(2)O(2) generation. In horse and human thyroid, an inconstant effect was observed. We demonstrate in dogs that the stimulatory effect of iodide is greater in thyroids deprived of iodide, raising the possibility that differences in thyroid iodide pool may account, at least in part, for the differences between the different species studied. This represents the first demonstration of an activation by iodide of a specialized thyroid function. In comparison with conditions in which an inhibitory effect of iodide on H(2)O(2) generation is observed, the stimulating effect was observed for lower concentrations and for a shorter incubation time with iodide. Such a dual control of H(2)O(2) generation by iodide has the physiological interest of promoting an efficient oxidation of iodide when the substrate is provided to a deficient gland and of avoiding excessive oxidation of iodide and thus synthesis of thyroid hormones when it is in excess. The activation of H(2)O(2) generation may also explain the well described toxic effect of acute administration of iodide on iodine-depleted thyroids.

Animals↗

PubMedDate not supplied

Quantification of Ca2+-activated K+ channels under hormonal control in pig pancreas acinar cells.

Ca2+- and voltage-activated K+ channels are found in many electrically excitable cells and have an important role in regulating electrical activity. Recently, the large K+ channel has been found in the baso-lateral plasma membranes of salivary gland acinar cells, where it may be important in the regulation of salt transport. Using patch-clamp methods to record single-channel currents from excised fragments of baso-lateral acinar cell membranes in combination with current recordings from isolated single acinar cells and two- and three-cell clusters, we have now for the first time characterized the K+ channels quantitatively. In pig pancreatic acini there are 25-60 K+ channels per cell with a maximal single channel conductance of about 200 pS. We have quantified the relationship between internal ionized Ca2+ concentration [( Ca2+]i) membrane potential and open-state probability (p) of the K+ channel. By comparing curves obtained from excised patches relating membrane potential to p, at different levels of [Ca2+]i, with similar curves obtained from intact cells, [Ca2+]i in resting acinar cells was found to be between 10(-8) and 10(-7) M. In microelectrode experiments acetylcholine (ACh), gastrin-cholecystokinin (CCK) as well as bombesin peptides evoked Ca2+-dependent opening of the K+ conductance pathway, resulting in membrane hyperpolarization. The large K+ channel, which is under strict dual control by internal Ca2+ and voltage, may provide a crucial link between hormone-evoked increase in internal Ca2+ concentration and the resulting NaCl-rich fluid secretion.

Acetylcholine↗

PubMed1989

The zygotic control of Drosophila pair-rule gene expression. II. Spatial repression by gap and pair-rule gene products.

We examined gene expression patterns in certain single and double pair-rule mutant embryos to determine which of the largely repressive pair-rule gene interactions are most likely to be direct and which interactions are probably indirect. From these studies we conclude that: (i) hairy+ and even-skipped (eve+) regulate the fushi tarazu (ftz) gene; (ii) eve+ and runt+ regulate the hairy gene; (iii) runt+ regulates the eve gene; but, (iv) runt does not regulate the ftz gene pattern, and hairy does not regulate the eve gene pattern. These pair-rule interactions are not sufficient, however, to explain the periodicity of the hairy and eve patterns, so we examined specific gap gene mutant combinations to uncover their regulatory effects on these two genes. Our surprising observation is that the hairy and eve genes are expressed in embryos where the three key gap genes hunchback (hb), Krüppel (Kr), and knirps (kni) have been removed, indicating that these gap genes are not essential to activate the pair-rule genes. In fact, we show that in the absence of either hb+ or kni+, or both gap genes, the Kr+ product represses hairy expression. These results suggest that gap genes repress hairy expression in the interstripe regions, rather than activate hairy expression in the stripes. The molecular basis of pair-rule gene regulation by gap genes must involve some dual control mechanisms such that combinations of gap genes affect pair-rule transcription in a different manner than a single gap gene.

Animals↗

PubMed1989

Opposite central and peripheral control by endogenous opioids of intestinal motility in fed rats.

1. The effects of the inhibitors of endopeptidase EC 24.11, thiorphan and phosphoramidon administered i.c.v. (40 micrograms kg-1) i.p. (400 micrograms kg-1), or orally (400 micrograms kg-1), on intestinal motor activity in fed rats was compared to the effects of similar doses of the angiotensin converting enzyme inhibitor, captopril and the synthetic enkephalin analogue [D-Ala2 Met5] enkephalinamide (Dalamide). Drugs were administered alone or after pretreatment with naloxone or N-methyl levallorphan (300 micrograms kg-1, i.p.) given 10 min prior to gavage with a standard meal. 2. In control conditions, in the duodenum, the disruption of the migrating myoelectric complex (MMC) by gavage with a standard meal lasted between 105.6 and 119.1 min. This duration was significantly decreased by thiorphan (60.3 +/- 15.0 min), phosphoramidon (67.9 +/- 7.3 min), captopril (26.3 +/- 10.2 min) and Dalamide (42.4 +/- 9.6 min), administered i.c.v. 3. In contrast, after the i.p. administration of thiorphan, phosphoramidon and Dalamide the delay in the return of the MMC pattern was increased. Such an effect was also seen after the oral administration of phosphoramidon or Dalamide. Neither i.p. nor oral captopril administration altered the duration of postprandial pattern. 4. A prior treatment with naloxone i.p. (300 micrograms kg-1) that had no effect per se, antagonized the effect produced by i.c.v. administration of thiorphan, phosphoramidon or Dalamide, but failed to reverse the effect of captopril. In contrast, i.p. administration of N-methyl levallorphan (300pgkg-1) did not affect the response induced by central administration of thiorphan, phosphoramidon, captopril or Dalamide, but was able to prevent that of thiorphan, phosphoramidon or Dalamide when they were administered i.p. or orally. 5. These data strongly support the hypothesis of a dual control by endogenous opioids of intestinal motility in the rat: a central component that favours, and a peripheral control that delays the occurrence of the MMC profile in fed rats.

Administration, Oral↗

PubMed1991

Inhibin and oestradiol in the control of FSH secretion in the sheep.

In the sheep both FSH and LH are necessary for development of large antral follicles. The secretion of FSH is controlled by the negative feedback effect of two ovarian hormones, oestradiol and inhibin, acting at the level of the anterior pituitary. Both are derived from the granulosa cells of large antral follicles which are present in sheep ovaries throughout the oestrous cycle. FSH stimulates growth and mitosis and so the fully differentiated granulosa cells of the large preovulatory follicles acquire receptors for LH, have maximal aromatase activity and produce large amounts of inhibin. The number of these large antral follicles (oestrogenic) which have the potential for ovulation corresponds to the ovulation rate specific for each particular breed of sheep. Over 90% of the oestradiol secreted by the ovaries is derived from these chosen follicles. In contrast, inhibin (and androstenedione) is also secreted by large antral follicles which have lost or not yet acquired maximal aromatase activity. The secretion of oestradiol by the preovulatory follicle(s) is dependent on the supply of androgen precursors produced by the theca which is stimulated by LH. When the concentration of progesterone falls at the end of the luteal phase the increased secretion of LH stimulates the progressive increase in secretion of oestradiol which occurs during the follicular phase. At this stage of the cycle there is a modest inconsistent rise in inhibin, the secretion of which is not stimulated by LH but is related to the increase in the number of large antral follicles. It is suggested that inhibin with its long half-life sets the overall level of negative feedback while oestradiol is responsible for the day-to-day fluctuations in the concentration of FSH which determines the number of ovulatory follicles. This dual control of FSH is adapted to monitor both the total number of large antral follicles in the ovaries (inhibin) and the number which are selected for ovulation (oestradiol).

Animals↗

PubMed1981

Regulation of glucose metabolism in pancreatic islets.

We evaluated the possible role of islet glucokinase in controlling the rate of islet glucose metabolism, and thereby the rate of glucose-induced insulin release. The activities of glucokinase, hexokinase, P-fructokinase, and glyceraldehyde-P dehydrogenase were quantitated in sonicated or isotonically homogenized islet preparations using pyridine nucleotide-dependent fluorometric assays. In sonicates, about 1/4 of the islet glucose phosphorylating activity was due to an enzyme with kinetic properties similar to glucokinase; 3/4 of the activity was due to hexokinase. The procedure for determining islet glucokinase activity was improved by centrifuging isotonic islet homogenates at 12,000 x g. The supernatant fraction was enriched for glucokinase. About 1/2 of the glucose phosphorylating activity in this fraction was due to glucokinase and 1/2 was due to hexokinase. The glucokinase activity in islet homogenates was !23 of the activity of hexokinase, 1/40 of the activity of P-fructokinase, and 1/400 of the activity of glyceraldehyde-P dehydrogenase. Detailed concentration dependency curves of glucose and mannose utilization were also obtained with intact isolated pancreatic rat islets. Glucose and mannose usage in islets was governed by two superimposed hyperbolic systems differing in Km and Vmax. A high Km system (Km for glucose 11 mM and for mannose 21 mM) predominated. A low Km system (Km for glucose 215 and for mannose 530 microM) contributed about 15% to the total activity. The available data with intact islets could be rationalized by the existence of two distinct hexose phosphorylating enzymes with differing capacities and kinetic properties. These enzymes, tentatively identified as glucokinase and hexokinase, could coexist in the same cell or could be distributed among different cell types. The possible physiologic significance of these results is discussed, emphasizing the idea of dual control of glycolysis and insulin release by glucokinase and hexokinase. An earlier proposal that glucokinase serves as glucoreceptor of beta-cells [J. Biol. Chem. 243:2730 (1968)] is greatly strengthened by the present studies.

Animals↗

PubMed2002

A randomized, placebo controlled trial of an antisense oligodeoxynucleotide to intercellular adhesion molecule-1 in the treatment of severe rheumatoid arthritis.

OBJECTIVE: To determine the safety of an antisense oligodeoxynucleotide to intercellular adhesion molecule-1 (ICAM-1) (ISIS 2302), administered in an intensive 4 week regimen with dose escalation; and to provide preliminary evidence for efficacy in rheumatoid arthritis (RA). METHODS: Patients with active RA were enrolled in a 6 month, double blind, placebo controlled, dual center, dose escalation (0.5, 1, and 2 mg/kg) study. Subjects received a total of 13 intravenous ISIS 2302 infusions, given on alternate days for 2 weeks and then 3 times a week for another 2 weeks. Doses of corticosteroids (< or = 10 mg/day) and disease modifying antirheumatic drugs (stable > or = 3 months) remained constant throughout the study. The primary efficacy endpoint was the Day 26 Paulus index, with secondary evaluations at Months 2-6. RESULTS: A total of 43 patients were enrolled with 11, 10, 3, and 19 patients receiving placebo or 0.5, 1, or 2 mg/kg of ISIS 2302, respectively. There were no differences between groups after randomization and the mean baseline swollen joint count was 22.5. Pharmacokinetic studies revealed a T(1/2) of 63 min and first-order kinetics with slight dose dependency, suggesting a saturable clearance process, although no accumulation was noted with repeat dosing. The Paulus 20% responses at Day 26 were 20%, 0%, and 5% for patients treated with ISIS 2302 (0.5, 1, 2 mg/kg, respectively) and 36% with placebo. For Months 2-6, the average intent-to-treat Paulus 20% responses were 21.2% for ISIS 2302 and 12.6% for placebo. Only ISIS 2302 treated subjects (19%) achieved Paulus 50% responses. ISIS 2302 was well tolerated. An expected and transient mean activated partial thromboplastin time increase of roughly 7 s was observed at the highest dose (2 mg/kg), as were small and clinically insignificant increases in serum C3a levels. T/B cell immunophenotyping, recall antigen skin testing, and serum immunoglobulin levels revealed no significant immunosuppressive effects. CONCLUSION: This study shows that 13 ISIS 2302 infusions over 4 weeks are well tolerated in patients with active RA. Although significant efficacy was not evident at the primary endpoint (1 month), the study lacked sufficient power to draw any formal conclusions. We tested a 4-fold drug concentration range, which led to a lower area under the curve range than was therapeutic in a subsequent Crohn's disease trial. Any further evaluation of this well tolerated ICAM-1 antisense agent should therefore be conducted at higher dosing.

Adolescent↗

PubMed1993

Two GnRHs fluctuate in correlation with androgen levels in the male frog Rana esculenta.

ChickenII-(cII-) and salmon (s-) GnRH levels have been measured in the male frog Rana esculenta during the annual cycle. The presence of pituitary binding activity for both peptides and plasma androgen levels has been investigated in order to give insight into the significance of the dual control exerted by the GnRH forms present in the R. esculenta brain. ChickenII- and s-GnRHs showed high values during the spring-summer period. Conversely, while cII-GnRH peaked in February, s-GnRH declined slowly from February until May. Plasma androgen levels increased as the peptides decreased during the autumn-winter period. Still high androgen levels (but significantly lower as compared with winter concentrations) were found during spring. Using iodinated cII-GnRH, GnRH binding sites were detected in pituitary preparations when the corresponding peptide concentration decreased in the brain. On the contrary, no binding sites were found using labeled s-GnRH. Our results indicate that cII-GnRH has a hypophysiotropic activity, while the role of s-GnRH needs to be further investigated.

Androgens↗

PubMed2002

The human monocarboxylate transporter, MCT1: genomic organization and promoter analysis.

Uptake of butyrate across the colonocyte luminal membrane is mediated by the monocarboxylate transporter isoform 1 (MCT1). We have demonstrated previously that expression of human colonic MCT1 is responsive to butyrate, and that this involves the dual control of MCT1 gene transcription and stability of the MCT1 transcript. Here we describe the structural organization of the human MCT1 gene, and report the isolation and characterization of the MCT1 gene promoter. The MCT1 gene spans approximately 44 kb, and is organized as 5 exons intervened by 4 introns. The first of these introns is located in the 5'-UTR-encoding DNA, spans >26 kb, and thus accounts for approximately 60% of the entire transcription unit. Analysis of a 1.5 kb fragment of the MCT1 5'-flanking region, shows an absence of the classical TATA-Box motif. However, the region contains potential binding sites for a variety of transcription factors with known association with butyrate's action in the colon. In transient transfections the 5'-flanking region drives high-level expression of a luciferase reporter-gene in cells that endogenously express MCT1. Deletion analyses indicate that the cis-acting elements necessary for basal transcription of MCT1 are contained within the -70/+213 proximal sequence of the promoter.

3' Untranslated Regions↗

PubMed2001

Hormonal regulation and patterning of the broad-complex in the epidermis and wing discs of the tobacco hornworm, Manduca sexta.

Expression of Manduca Broad-Complex (BR-C) mRNA in the larval epidermis is under the dual control of ecdysone and juvenile hormone (JH). Immunocytochemistry with antibodies that recognize the core, Z2, and Z4 domains of Manduca BR-C proteins showed that BR-C appearance not only temporally correlates with pupal commitment of the epidermis on day 3 of the fifth (final) larval instar, but also occurs in a strict spatial pattern within the abdominal segment similar to that seen for the loss of sensitivity to JH. Levels of Z2 and Z4 BR-C proteins shift with Z2 predominating at pupal commitment and Z4 dominant during early pupal cuticle synthesis. Both induction of BR-C mRNA in the epidermis by 20-hydroxyecdysone (20E) and its suppression by JH were shown to be independent of new protein synthesis. For suppression JH must be present during the initial exposure to 20E. When JH was given 6 h after 20E, suppression was only seen in those regions that had not yet expressed BR-C. In the wing discs BR-C was first detected earlier 1.5 days after ecdysis, coincident with the pupal commitment of the wing. Our findings suggest that BR-C expression is one of the first molecular events underlying pupal commitment of both epidermis and wing discs.

Animals↗