Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ligand specificity and biochemical properties of the human (h) FSH receptor are poorly characterized due to the low abundance of these receptors and the limited availability of human tissues. Using a fragment of rat FSH receptor cDNA, we screened a human testicular cDNA library and obtained a FSH receptor cDNA covering the entire amino acid-coding region. After transfection of a human fetal kidney cell line (293) with the hFSH receptor cDNA, radioligand receptor analysis revealed the presence of high affinity (Kd, 1.7 x 10(-9) M) FSH-binding sites on the plasma membrane. Both recombinant and wild-type hFSH displaced [125I]hFSH binding, with ED50 values of 25 and 70 ng/ml, respectively, whereas hLH, hCG, and hTSH were ineffective. Although human, rat(r), and ovine FSH as well as equine CG competed for rat testicular FSH receptor binding, only hFSH and rFSH interacted effectively with the recombinant hFSH receptor, suggesting that species-specific ligand recognition exists between human and rodent receptors. After incubation of transfected cells with hFSH, but not recombinant hLH or hCG, a dose-dependent increase (ED50, 10 ng/ml) in extracellular cAMP accumulation was observed, indicating a functional coupling of the expressed human receptor with the endogenous adenyl cyclase. In cells cotransfected with the FSH receptor expression plasmid and a luciferase reporter gene driven by the promoter of a cAMP-responsive gene, treatment with hFSH, but not hCG, resulted in a dose-dependent increase in luciferase activity. Northern blot analysis using a cRNA probe derived from the human receptor cDNA indicated the presence of multiple FSH receptor mRNA transcripts (7.0, 4.2, and 2.5 kilobases) in RNA prepared from human follicular phase ovary, but not from human corpus luteum or placenta. Additionally, two FSH-binding sites of 76 and 112 kilodaltons were detected in transfected 293 cells after ligand/receptor cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. These results demonstrate the expression of functional hFSH receptor with unique ligand specificity and provide new data on the biochemical properties of the human receptor at the mRNA and protein levels.
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PMID:Expression of recombinant human follicle-stimulating hormone receptor: species-specific ligand binding, signal transduction, and identification of multiple ovarian messenger ribonucleic acid transcripts. 132 83

Fetal exposure to high doses of glucocorticoids slows cellular development and impairs organ performance, in association with growth retardation. Nevertheless, low doses of glucocorticoids may enhance cell differentiation and accelerate specific functions. The current study examined this apparent paradox in the developing rat kidney, using doses of dexamethasone that span the threshold for growth impairment: 0.05 or 0.2 mg/kg given on gestational days 17, 18 and 19. At the lower dose, which did not significantly retard body growth, the postnatal development of tubular reabsorptive capabilities for sodium, potassium, osmotic particles, water and urea was accelerated. These effects were less notable at the higher dose, which caused initial body growth impairment. The selectivity toward promotion of tubular function was evidenced by the absence of effect of either dose of dexamethasone on development of glomerular filtration rate. Because of the wide spectrum of dexamethasone's effects on tubular function, we also assessed fetal kidney adenylate cyclase as a means of detecting altered cell differentiation in the prenatal period during which dexamethasone was given. Either glucocorticoid dose increased the total adenylate cyclase catalytic activity (assessed with forskolin). Thus, the net effect of fetal dexamethasone exposure on development of renal excretory capabilities probably represents the summation of promoted cell differentiation and slowed development consequent to growth retardation. At low dose levels, the former effect predominates, leading to enhanced functional development, whereas higher doses that interfere with general growth and development can offset the direct promotional effect.
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PMID:Fetal dexamethasone exposure accelerates development of renal function: relationship to dose, cell differentiation and growth inhibition. 150 Jun 34

Evidence for the expression of genes of the renin-angiotensin system (RAS) in the developing kidney is rapidly accumulating. We have recently demonstrated that the fetal kidney expresses the renin gene and that expression of the gene is developmentally regulated. Kidney renin messenger ribonucleic acid (mRNA) levels decrease markedly with maturation, and as maturation unfolds the intrarenal distribution of renin and its mRNA changes from large intrarenal arteries in the fetus to a restricted juxtaglomerular site in the adult animal. These findings demonstrate that renin is synthesized and stored in the aforementioned vascular segments and that expression of the renin gene follows the centrifugal pattern of nephrovascular development. In addition to storing renin, intact kidney microvessels release renin spontaneously and possess a functionally active adenylate cyclase whose stimulation results in a marked increase in renin release. The increase in renin enzymatic activity appears to be due to a recruitment of renin-releasing cells rather than to an increase in the amount of renin secreted per cell. Expression of the angiotensinogen (Ao) gene is also developmentally regulated. Ao mRNA levels are very low in the fetal liver, markedly increasing after parturition, suggesting that some of the complex neurohumoral changes surrounding extrauterine life may regulate the expression of the Ao gene. As in the adult animal, Ao is expressed in fetal kidney, brain and brown adipose tissue. The contribution of these organs to the fetal plasma pool of Ao remains to be determined. However, unlike the adult, the fetal liver may not be the primary source of circulating Ao in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular biology of components of the renin-angiotensin system during development. 220 11

During the last third of pregnancy, the rat phospho-calcic metabolism is clearly modified. Sensitivity of the renal receptor to parathormone (PTH) was investigated over this period in the fetuses and their mothers. As early as day 16.5 of pregnancy, the fetal kidney is sensitive to bovine PTH (1-34) on the basis of cAMP production. Sensitivity declines on the last day of pregnancy. The newborn kidney showed a higher response to PTH 3 h after birth than after 24 h. The basal adenylate cyclase activity in renal membranes of maternal kidney does not change. The sensitivity to PTH and to fluoride both decreased on day 18.5. A desensitization process of the PTH receptor A-C system has to be studied in order to explain these results.
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PMID:Sensitivity of the renal adenylate cyclase receptor system to parathormone during the last third of pregnancy in the rat. 254 86

The effect of maternal hyperosmolality as created by an acute mannitol infusion was evaluated in eight chronic sheep preparations. Fetal osmotic and haemodynamic responses were compared to those achieved during an arginine vasopressin (AVP) infusion into the fetus (approximately 400 microU/(min kg]. To assess the AVP sensitivity of the fetal kidney the urine osmolality was determined. The activity of adenylate cyclase was measured in placental cotyledons as an indicator of AVP receptors affecting water permeability. The maternal mannitol infusion induced an increase in fetal serum AVP levels from 1.18 +/- 0.25 up to 13.76 +/- 2.11 pg/ml. During the fetal AVP infusion the AVP levels were approximately 22 pg/ml, somewhat higher when given concurrently with a mannitol infusion to the ewe (peak value: 26.13 +/- 2.80 pg/ml). Fetal heart rate increased significantly during maternal hyperosmolality while this effect was blunted by exogenous AVP given to the fetus. The AVP infusion did not affect fetal or maternal serum osmolality. During the mannitol infusion fetal serum osmolality increased to peak values which were not significantly different whether or not AVP was infused into the fetus (from 298.0 +/- 0.85 to 309.0 +/- 0.90, and from 297.7 +/- 1.47 to 307.9 +/- 0.90 mosmol/kg, respectively). Similarly, there were no differences in the effect of mannitol infusion upon fetal urine osmolality with or without AVP infusion (increments: + 149.7 +/- 34.12 and + 148.7 +/- 31.30 mosmol/kg, respectively). Adenylate cyclase activity in the placenta was unchanged before and after AVP stimulation. The data suggest an unresponsiveness of placental water permeability to fetal AVP infusion. We also conclude that a maximal urine osmolality was reached already at AVP levels obtained after an osmotic maternal load whereas at AVP levels more than twice as high the cardiovascular effects were still AVP dose-dependent.
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PMID:Ovine fetal response to water deprivation: aspects on the role of vasopressin. 314 61