Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.1.1.32 (phosphoenolpyruvate carboxykinase)
4,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xenopus laevis (Daudin) adult specimens were submitted to hypophysectomy. Although the operation resulted subtotal, it served the purpose of removing the prolactin-producing cells, whereby the involvement of endogenous prolactin in osmoregulation phenomena was excluded. In the operated animals treated with ovine prolactin the following metabolic parameters, which are closely dependent upon interrenal activity, were estimated: 1) intestine alkaline phosphomonoesterase activity (E.C. 3.1.3.1); 2) liver glycogen level; 3) glucose-6-phosphatase (E.C. 3.1.3.9.) and phosphoenolpyruvate carboxykinase (E.C. 4.1.1.32.) in the liver; 4) blood glucose level; 5) blood ammonia and urea levels; 6) carbamoylphosphate synthetase activity in the liver (E.C. 2.7.2.a); 7) muscle sodium and potassium levels. The above metabolic parameters were found to be pressed by subtotal hypophysectomy and after subsequent prolactin treatment showed the tendency to go back to values similar to those of control animals.
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PMID:Biochemical data on subtotally hypophysectomized Xenopus laevis (Daudin) adult specimens treated or not with prolactin. 21 25

The somatotropic and lactotropic receptors were studied in liver microsomal preparations from transgenic mice carrying the human growth hormone (hGH) or bovine growth hormone (bGH) gene fused to mouse metallothionein-I (MT) or phosphoenolpyruvate carboxykinase promoter/regulator (PEPCK). Specificity studies indicated that, similarly to normal mice, liver microsomes from the transgenic animals possess a mixed population of somatotropic and lactotropic binding sites. In transgenic animals of both sexes, the binding capacity of somatotropic receptors was significantly increased without corresponding changes in affinity. Expression of the MT-hGH hybrid gene was associated with the induction of somatotropic receptors which was approximately twice as great as that measured in animals expressing the MT-bGH hybrid gene. The binding capacity of lactotropic receptors in liver microsomes (quantitated by the use of labelled ovine prolactin) was increased 2-3 fold in transgenic females and approximately 10-fold in transgenic males as compared to the respective normal controls. We conclude that lifelong excess of GH up-regulates hepatic GH and prolactin receptors, and that lactogenic activity of GH is not essential for induction of prolactin receptors in the liver of transgenic mice.
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PMID:Somatotropic and lactotropic receptors in transgenic mice expressing human or bovine growth hormone genes. 130 Dec 13

Reproductive performance was studied in transgenic males from lines expressing and transmitting four hybrid genes: mouse metallothionein-I/human growth hormone (GH) (MT/hGH), MT/hGH placental variant (MT/hGH.V), MT/bovine GH (MT/bGH) and phosphoenolpyruvate carboxykinase/bGH (PEPCK/bGH). Each male was exposed to three normal females for 1 week and to three different normal females for another week. Females were examined for vaginal plugs and necropsied on day 14 of pregnancy. Males were killed for analysis of organ weights, numbers of testicular spermatids, numbers of epididymal sperm and measurements of plasma glucose concentration. Fertility of MT/hGH and MT/hGH.V transgenic males was significantly lower than in normal males, primarily because most males failed to impregnate any females. In females that became pregnant, the numbers of corpora lutea, total fetuses and live fetuses did not differ from those in females mated to normal (nontransgenic) males. Fetal crown-rump length on day 14 of pregnancy did not differ between litters sired by normal or by transgenic males. Weights of testes and seminal vesicles were significantly greater in all four types of transgenic male, but daily sperm production per unit weight (g-1) of testis was not affected and epididymal sperm reserves were either normal or slightly higher than normal. Plasma glucose concentrations were significantly higher in PEPCK/bGH mice than in other mice. Average or individual reproductive performance of transgenic males from the various lines did not correlate with any of the parameters examined except for significantly heavier seminal vesicles in MT/hGH and MT/hGH.V males than in normal males; these transgenic males exhibited a high incidence of infertility. Since hGH and hGH.V, but not bGH, are lactogenic in rodents, it was concluded that chronic stimulation of GH and prolactin receptors by ectopically produced human GHs in transgenic mice compromises male fertility by an unknown mechanism. Reduced fertility of transgenic males with MT/hGH or MT/hGH.V hybrid genes is due to failure to inseminate or impregnate females rather than to reduced numbers of spermatozoa or gross changes in the male reproductive system.
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PMID:Effects of expression of human or bovine growth hormone genes on sperm production and male reproductive performance in four lines of transgenic mice. 162 26

By comparing the 5'-flanking region of the porcine gene for the urokinase form of plasminogen activator with those of other cAMP-regulated genes, we identify a 29-nucleotide sequence that is tentatively proposed as the cAMP-regulatory unit. Homologous sequences are present (i) in the cAMP-regulated rat tyrosine aminotransferase, prolactin, and phosphoenolpyruvate carboxykinase genes and (ii) 5' to the transcription initiation sites of cAMP-regulated Escherichia coli genes. From this we conclude that the expression of cAMP-responsive genes in higher eukaryotes may be controlled, as in E. coli, by proteins that form complexes with cAMP and then show sequence-specific DNA-binding properties. The complex formed by cAMP and the regulatory subunit of the type II mammalian protein kinase might be one candidate for this function. Based on several homologies we suggest that this subunit may have retained both the DNA-binding specificity and transcription-regulating properties in addition to the nucleotide-binding domains of the bacterial cAMP-binding protein. If this were so, dissociation of protein kinase by cAMP would activate two processes: (i) protein phosphorylation by the catalytic subunit and (ii) transcription regulation by the regulatory subunit.
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PMID:Gene expression and cAMP. 299 82

The mechanism by which individual peptide and steroid hormones and cell-substratum interactions regulate milk protein gene expression has been studied in the COMMA-D mammary epithelial cell line. In the presence of insulin, hydrocortisone, and prolactin, growth of COMMA-D cells on floating collagen gels in comparison with that on a plastic substratum resulted in a 2.5- to 3-fold increase in the relative rate of beta-casein gene transcription but a 37-fold increase in beta-casein mRNA accumulation. In contrast, whey acidic protein gene transcription was constitutive in COMMA-D cells grown on either substratum, but its mRNA was unstable and little intact mature mRNA was detected. Culturing COMMA-D cells on collagen also promoted increased expression of other genes expressed in differentiated mammary epithelial cells, including those encoding alpha- and gamma-casein, transferrin, malic enzyme, and phosphoenolpyruvate carboxykinase but decreased the expression of actin and histone genes. Using COMMA-D cells, we defined further the role of individual hormones in influencing beta-casein gene transcription. With insulin alone, a basal level of beta-casein gene transcription was detected in COMMA-D cells grown on floating collagen gels. Addition of prolactin but not hydrocortisone resulted in a 2.5- to 3.0-fold increase in beta-casein gene transcription, but both hormones were required to elicit the maximal 73-fold induction in mRNA accumulation. This posttranscriptional effect of hormones on casein mRNA accumulation preceded any detectable changes in the relative rate of transcription. Thus, regulation by both hormones and cell substratum of casein gene expression is exerted primarily at the post transcriptional level.
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PMID:Both cell substratum regulation and hormonal regulation of milk protein gene expression are exerted primarily at the posttranscriptional level. 306 79

The administration of 2 bromo-alpha-ergocryptine, to reduce serum prolactin decreased the activity of cytosolic P-enolpyruvate carboxykinase (GTP) (EC 4.1.1.32) about 50% in both liver and mammary gland of lactating animals. Adrenalectomy had similar effects to those of bromo-alpha-ergocryptine. In contrast, there was a 50% increase in enzyme activity in the mammary gland of diabetic, lactating rats and a 10-fold increase in liver as compared with normal rats. P-enolpyruvate carboxykinase activity in mammary gland as liver is coordinately regulated by prolactin, glucocorticoids and insulin.
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PMID:Effect of prolactin and glucocorticoids on P-enolpyruvate carboxykinase activity in liver and mammary gland from diabetic and lactating rats. 402 4

Transgenic female mice overexpressing the bovine growth hormone (bGH) gene with the phosphoenolpyruvate carboxykinase (PEPCK) promoter exhibit severe reproductive deficits. Although these animals ovulate and conceive normally, pregnancy is arrested due to luteal failure, leading to the loss of embryos during early gestation. The results of replacement therapy suggested that luteal failure was secondary to prolactin (PRL) deficiency. The objective of this study was to examine the neuroendocrine control of PRL secretion during early pregnancy in PEPCKbGH-1 transgenic mice. Normal and transgenic littermates were killed by decapitation on Day 7 postcoitum (p.c.) at 1500, 1800, or 2100 h, i.e., the period including the expected diurnal PRL surge in pregnant mice. In normal females, plasma PRL levels were significantly elevated at 1800 h when compared to the levels measured at 1500 or 2100 h, but no temporal variation in PRL levels was found in transgenic mice. In normal females, the content of dopamine in the median eminence was reduced at 1800 h, i.e., at the time of the PRL surge. In contrast, no temporal changes were detected in the median eminence dopamine content in transgenic mice. Twice-daily injections of domperidone, a dopamine receptor blocker, increased the incidence of pregnancy in transgenic females. After treatment with aromatic amino acid decarboxylase inhibitor NSD-1015 on Day 7 p.c., plasma levels of PRL were similarly elevated in transgenic and normal females. However, the accumulation of 5-hydroxytryptophan (5-HTP) in the medial basal hypothalamus after this treatment was significantly smaller in transgenic than in normal females.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Infertility in transgenic mice overexpressing the bovine growth hormone gene: disruption of the neuroendocrine control of prolactin secretion during pregnancy. 762 19

Overexpression of human (h) or bovine (b) growth hormone (GH) in transgenic mice is associated with marked (2- to 12-fold) and significant increase in hepatic binding of GH and prolactin (PRL). This is due to an increase in the number of GH and PRL receptors (GHR, PRLR) per mg of microsomal protein without changes in binding affinity. Comparison of results obtained in transgenic animals expressing bGH with a mouse metallothionein (MT) or a rat phosphoenolpyruvate carboxykinase (PEPCK) promoter suggests that effects of bGH on hepatic GHR and PRLR do not require GH overexpression during fetal life and, within the dose range tested, the effects on PRLR are not dose dependent. The increase in hepatic GHR was accompanied by significant increases in plasma GH-binding protein (GHBP) and in mean residence time of injected GH. Thus, life-long elevation of peripheral GH levels alters the availability of both free GH and GHR. Site-directed in vitro mutagenesis was used to produce hGH and bGH analogs mutated within one of the sites involved in binding to GHR and PRLR. Mutating hGH to produce amino acid identity with bGH at Position 11, 18 (within Helix 1), 57, or 60 (within the loop between Helix 1 and 2) did not affect binding to GHR in vitro, or somatotropic activity in transgenic mice in vivo but reduced lactogenic activity in Nb2 cells by 22%-45%. Mutations of bGH designed to produce amino acid identity with hGH at one to four of the corresponding positions in the bGH molecule did not interfere with binding to GHR or somatotropic activity in vivo, and failed to produce significant binding to PRLR but resulted in alterations in the effects on the hypothalamic and anterior pituitary function in transgenic mice. Apparently region(s) outside the domains examined are essential for lactogenic activity of hGH, and different portions of the GH molecule are responsible for its diverse actions in vivo.
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PMID:Growth hormone (GH) binding and effects of GH analogs in transgenic mice. 801 52

Availability of recombinant growth hormone (GH) and development of long-acting formulations of this material will undoubtedly lead to widespread use of GH in animal industry and in medicine. GH can act, directly or indirectly, on multiple targets, but its influence on the reproductive system and on the hormonal control of reproduction is poorly understood. Overexpression of GH genes in transgenic animals provides a unique opportunity to study the effects of long-term GH excess. Transgenic mice overexpressing bovine, ovine, or rat GH (hormones with actions closely resembling, if not identical to, those of endogenous [mouse] GH), exhibit enhancement of growth, increased adult body size, and reduced life-span as well as a number of endocrine and reproductive abnormalities. Ectopic overexpression of bovine GH (bGH) driven by metallothionein or phosphoenolpyruvate carboxykinase promoters is associated with altered activity of hypothalamic neurons which produce somatostatin, loss of adenohypophyseal GH releasing hormone (GHRH) receptors, and suppression of endogenous (mouse) GH release. Elevation of plasma levels of GH (primarily bGH) and insulin-like growth factor (IGF-I) in these transgenic mice leads to increases in the number of hepatic GH and prolactin (PRL) receptors, in the serum levels of GH-binding protein (GHBP), in the percent of GHBP complexed with GH, and in the circulating insulin levels. In addition, plasma adrenocorticotropic hormone (ACTH) and corticosterone levels are elevated. Plasma levels of luteinizing hormone (LH), as well as its synthesis and release, are not consistently affected, but follicle-stimulating hormone (FSH) levels are suppressed, apparently due to pre- and post-translational effects. Pituitary lactotrophs exhibit characteristics of chronic enhancement of secretory activity, and plasma PRL levels are elevated. Prolactin responses to mating or to pharmacological blockade of dopamine synthesis are abnormal. Reproductive life span and efficiency are reduced in both sexes, with the severity and frequency of reproductive deficits being related to plasma bGH levels. Most transgenic females expressing high levels of bGH are sterile due to luteal failure. Overexpression of human GH which, in the mouse, interacts with both GH and PRL receptors leads to additional endocrine and reproductive abnormalities including stimulation of LH beta mRNA levels and LH secretion, loss of responsiveness to testosterone feedback, overstimulation of mammary glands, enhanced mammary tumorigenesis, and hypertrophy of accessory reproductive glands in males.
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PMID:Neuroendocrine and reproductive consequences of overexpression of growth hormone in transgenic mice. 807 44

Pituitary somatotrophs are suppressed in mice transgenic for human (h) or bovine (b) growth hormone (GH) genes fused with metallothionein (MT) or phosphoenolpyruvate carboxykinase (PEPCK) promoters. Previous morphologic studies revealed that lactotrophs are inhibited in hGH transgenic lines probably due to prolactin-like effects of hGH whereas in female bGH transgenics, the lactotrophs are stimulated. In the present study, estrogen receptor (ERalpha) mRNA was studied by autoradiographic in situ hybridization (ISH), ERalpha protein by immunocytochemistry, and dopamine subtype 2 receptor (D2R) mRNA by ISH. In MT/ and PEPCK/hGH transgenic mice, silver grains signaling ERalpha mRNA were significantly decreased compared to controls; the reduction was stronger in males (8.6 and 37%) than in females (4.6 and 11%). The decrease in the number of ERalpha-immunoreactive nuclei followed the same pattern (13.3 and 6% in males vs 3.2 and 5.2% in females). In MT/hGH mice the D2R mRNA signal was significantly increased in males (6 and 15.4%) and females (16%). In MT/bGH transgenics, ERalpha mRNA and ERalpha-immunoreactive nuclei were significantly increased (25 and 6%) only in males; D2R mRNA was more decreased in females (23%) than in males (15%). In conclusion, the opposite changes in ERalpha and D2R gene expressions are correlated with lactotroph inhibition in hGH transgenic mice and their stimulation in bGH transgenic mice. The changes in ERalpha expression were stronger in males, whereas those of D2R were more pronounced in females.
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PMID:Pituitary estrogen receptor alpha and dopamine subtype 2 receptor gene expression in transgenic mice with overproduction of heterologous growth hormones. 1009 20


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