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

---

Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The maturation of ovarian granulosa cells is dependent upon the pituitary gonadotropin FSH, the actions of which are mediated via specific plasma membrane receptors. To study the regulation of ovarian FSH receptor expression at the mRNA level, we used a specific cRNA probe to evaluate changes in FSH receptor transcripts in cultured granulosa cells. Granulosa cells obtained from immature estrogen-treated rats contained two predominant FSH receptor mRNA transcripts (7.0 and 2.5 kilobases), the levels of which declined in a time-related manner during a 2-day culture period. However, inclusion of FSH (30 ng/ml) in the culture medium prevented the decline in FSH receptor mRNA levels. Compared to controls, treatment of granulosa cells for 48 h with FSH (1-100 ng/ml) increased FSH receptor mRNA levels in a dose-dependent manner (ED50, 4.5 ng/ml), with a maximal 5.9 +/- 0.7-fold increase observed in response to 30 ng/ml FSH. The stimulatory actions of FSH were mimicked by the adenyl cyclase activator forskolin (0.1-30 microM), suggesting the involvement of cAMP in FSH receptor gene transcription and/or mRNA stability. Incubation of granulosa cells for 48 h with epidermal growth factor (EGF; 0.3-10 ng/ml), basic fibroblast growth factor (bFGF; 1-30 ng/ml), or insulin-like growth factor-I (IGF-I; 1-30 ng/ml) did not affect basal FSH receptor mRNA levels, whereas the highest doses of EGF and bFGF, but not IGF-I, completely suppressed the stimulatory effects of FSH (30 ng/ml) on its own receptor mRNA levels. Similarly, GnRH (10-1000 nM) attenuated the actions of FSH on its receptor mRNA levels in a dose-dependent manner (ID50, 8 nM). The inhibitory effects of GnRH (100 nM) were reversed by cotreatment with a GnRH antagonist ([Ac-D-Phe1,D-pCl-Phe2,D-Trp3,6]GnRH; 100 nM), indicating that the actions of GnRH are mediated via specific GnRH receptors. These data indicate that treatment of granulosa cells with FSH increases the levels of two FSH receptor mRNA transcripts. However, this positive feedback system, which may lead to an amplification of FSH action, is tightly regulated by the inhibitory actions of EGF, bFGF, and GnRH. Thus, the use of cultured rat granulosa cells provides a model system to analyze the hormonal regulation of FSH receptor gene expression in the ovary.
...
PMID:Hormonal regulation of follicle-stimulating hormone receptor messenger ribonucleic acid levels in cultured rat granulosa cells. 131 Dec 35

Injections of parathyroid hormone (PTH) result in increased bone formation in several species. Work in our laboratory and others has shown a stimulation of bone cell proliferation and growth factor production by PTH. Our purpose was to study the effects of PTH on a human bone cell line using TE-85 human osteosarcoma cells as a model. After 24 h treatment, PTH caused an increase in cell proliferation as measured by cell counts and [3H]-thymidine incorporation. Proliferation was not inhibited by an anti-transforming growth factor beta (TGF beta) antibody which could abolish stimulation by exogenous TGF beta. PTH did not stimulate cAMP production, alkaline phosphatase activity or production of insulin-like growth factors I or II (IGF-I or IGF-II) in TE-85 cells. Although basal TE-85 proliferation was slowed by incubation with the calcium channel blocking agent verapamil, PTH still caused an increase in growth rate. We conclude that PTH directly stimulates TE-85 proliferation via a mechanism not involving increased adenylate cyclase activity or increased secretion of IGF-I, IGF-II or TGF beta and may stimulate bone formation in vivo by activating some other mitogenic signal to increase bone cell proliferation.
...
PMID:PTH stimulates the proliferation of TE-85 human osteosarcoma cells by a mechanism not involving either increased cAMP or increased secretion of IGF-I, IGF-II or TGF beta. 131 2

Porcine granulosa cells (GC) produce insulin-like growth factor (IGF) binding protein (BP)-3 and IGFBP-2 in culture. A gonadotropin, follicle-stimulating hormone (FSH), dramatically inhibited GC production of these IGFBPs in control cultures and in cultures stimulated by insulin plus epidermal growth factor (EGF) or IGF-I plus EGF. Stimulators of adenylate cyclase (forskolin, cholera toxin) and a derivative of adenosine 3',5'-cyclic monophosphate (cAMP), 8-bromoadenosine 3',5'-cyclic monophosphate, inhibited IGFBP synthesis in a manner similar to FSH. In contrast, the antagonist of cAMP action, (R)-p-adenosine 3',5'-cyclic phosphorothioate [(R)-p-cAMPS], significantly stimulated production of IGFBP-3 and IGFBP-2 compared with controls. This stimulatory effect of (R)-p-cAMPS was counteracted by cotreatment with FSH in a dose-dependent manner. Finally, treatment of GC cultures with FSH plus 3-isobutyl-1-methylxanthine resulted in a significant reduction in cellular content of mRNA coding for IGFBP-3 with no change in IGFBP-2 mRNA. In summary, agents that elevate intracellular cAMP were found to mimic the effects of FSH on IGFBP production.
...
PMID:Gonadotropin and cAMP modulation of IGE binding protein production in ovarian granulosa cells. 137 63

Human decidual tissue synthesizes and secretes a protein that is identical to pituitary prolactin in its chemical, biological and immunological properties. Nevertheless, the factors that regulate the synthesis and release of prolactin from the decidual tissues appear to be different to those regulating the synthesis and release of pituitary prolactin. Studies from our laboratory over the past few years indicate that the synthesis and release of decidual prolactin are regulated, at least in part, by factors released by placenta, fetal membranes and decidua. The placenta releases a 23.5 KMr protein [decidual prolactin-releasing factor (PRL-RF)] that stimulates a rapid release of prolactin within the first few minutes of exposure and a sustained, prolonged, increase in the synthesis and release of prolactin beginning 6-8 h after exposure. The acute release of prolactin in response to PRL-RF is inhibited by decidual prolactin release-inhibitory factor (PRL-IF), a 35-45 K Mr protein that is released by the decidua. The secondary increase in the synthesis and release of prolactin in response to PRF-RF is blocked by lipocortin I, which is synthesized by both the placenta and decidua. IGF-I, insulin and relaxin also stimulate the synthesis and release of prolactin. However, the stimulation in response to these factors does not occur until 24-48 h after exposure. The cellular mechanisms involved in the release of decidual prolactin are as yet unknown. However, recent studies implicate activation of adenylate cyclase, phospholipase C-mediated phosphoinositide hydrolysis and phospholipase A2-mediated arachidonic acid release in the regulation of prolactin release. The finding that the synthesis and release of decidual prolactin are regulated, at least in part, by PRL-RF, IGF-I, insulin, relaxin and lipocortin I strongly suggests that there is novel feedback regulation between the placenta, fetal membranes, and decidua in the regulation of the synthesis and release of decidual prolactin.
...
PMID:Regulation of the synthesis and release of decidual prolactin by placental and autocrine/paracrine factors. 183 Dec 61

Bovine mammary undifferentiated epithelial cells from young female calves, cultured in three-dimensional collagen gels in serum-free medium exhibited ultrastructural organization that resembled the in vivo situation. Extracts of bovine pituitary, kidney, uterus and mammary gland, stimulated cell proliferation in a dose-dependent manner. This mitogenic activity strongly synergised with the existant growth factors (GFs) in FCS and with IGF-I, while the addition of EGF had only minor effect. No synergistic manifestation was found with cholera toxin but pertussis toxin inhibited the growth-promoting activity of all four extracts. Other experiments indicated that this mitogenic activity does not result from prolactin, growth hormone or fibroblast growth factor. The present and former results, in which synergism between IGF-I and cholera toxin was demonstrated, suggest therefore, that the mitogenesis of normal mammary epithelial cells regulated by several tissue derived growth factors, consists of at least two pathways which are distinct from those activated by EGF and IGF-I. One of these pathways indicates involvement of pertussis toxin-sensitive GTP-binding proteins, and the other, activation of cholera toxin-sensitive adenylate cyclase.
...
PMID:Bovine pituitary, kidney, uterine and mammary gland extracts contain bovine mammary epithelium growth factors that synergise with IGF-I and fetal calf serum: indication for involvement of GTP-binding proteins. 190 89

Studies from this laboratory indicate that the synthesis and release of prolactin from human decidual cells are regulated by factors released by the placenta, decidua and fetal membranes. A 23.5 kD protein (decidual prolactin-releasing factor, PRL-RF) has been purified to homogeneity from human placental tissue and placental conditioned medium. The releasing factor stimulates an acute release of prolactin that occurs within the first few minutes of exposure and a prolonged release, secondary to new hormone synthesis, that begins about 6-8 hours later. In addition, the synthesis and release of decidual prolactin are stimulated by IGF-I, insulin and relaxin, each acting through distinct plasma membrane receptors. In contrast, the synthesis and release of decidual prolactin are inhibited by arachidonic acid, lipocortin I and a 35-45 kD decidual protein (prolactin-releasing inhibitory factor) that has been partially purified from decidual conditioned medium. Studies of the second messengers involved in the regulation of decidual prolactin release strongly suggest that decidual prolactin release may be mediated, at least in part, by activation of phosphoinositide metabolism and stimulation of adenylate cyclase. The demonstration that the synthesis and release of decidual prolactin are regulated by PRL-RF, IGF-I, insulin, relaxin, arachidonic acid, PRL-IF and lipocortin I strongly suggests that there is novel autocrine/paracrine feedback regulation between the placenta, fetal membranes, and decidua in the regulation of decidual prolactin.
...
PMID:Autocrine/paracrine regulation of prolactin release from human decidual cells. 206 75

Characterization of insulin and type I insulin-like growth factor (IGF-I) receptors and the effects of insulin and IGF-I on steroidogenesis were evaluated by using purified adult Leydig cells from Sprague-Dawley rats. Purified Leydig cells were found to contain both high and low affinity binding sites for insulin, with Ka values of 1.08 X 10(9) and 1.1 X 10(7) M-1, respectively. Using affinity cross-linking of [125I]iodoinsulin to plasma membrane insulin receptor, several bands were identified by autoradiography under nonreduced conditions with mol wt of 230,000, 280,000, and 300,000. After reduction with 50 mM dithiothreitol, only one band was identified with a mol wt of 130,000, consistent with the alpha-subunit of insulin receptor. Purified Leydig cells also contain specific type I IGF receptors with estimated binding affinity of 0.6 X 10(9) M-1. Multiple high mol wt bands (greater than 250,000) were identified under nonreduced conditions by affinity cross-linking. Under reduced conditions, one band with an approximate mol wt of 135,000 was identified. Purified Leydig cells (10(5) cells/ml) were cultured in Dulbecco's Modified Eagle's Medium-Ham's F-12 Nutrient Mixture (1:1) containing 0.1% fetal calf serum at 37 C in a humidified atmosphere of 5% CO2-95% air. Insulin and IGF-I stimulated testosterone formation as early as 3 h after administration, and their effects were completely blocked by the addition of a protein synthesis inhibitor, cycloheximide (1 microgram/ml). Insulin and IGF-I also significantly potentiated hCG-and 8-bromo-cAMP-induced testosterone formation. Furthermore, insulin and IGF-I potentiated hCG-stimulated cAMP formation. This suggests that insulin and IGF-I have effects at both the LH receptor sites and the steps beyond adenylate cyclase. The ED50 values of insulin and IGF-I-stimulated testosterone formation were comparable (25 ng/ml). In conclusion, we found that Leydig cells contain specific insulin and type I IGF receptors, and both insulin and IGF-I are capable of modulating Leydig cell steroidogenesis.
...
PMID:Characterization of insulin and insulin-like growth factor I receptors of purified Leydig cells and their role in steroidogenesis in primary culture: a comparative study. 294 38

We have previously shown that insulin-like growth factor (IGF-I) suppresses basal and GHRH-induced GH gene transcription. cAMP is a putative intracellular mediator of GHRH action. We, therefore, studied the mechanism of IGF-I action on the somatotroph with or without cAMP activators. Primary rat pituitary cells growing in serum-free medium were treated with IGF-I. GH secretion was measured by RIA, and mRNA levels were measured by hybridization to [32P]GH cDNA. 8-Bromo-cAMP (8-Br-cAMP; 0.625 mM) stimulated GH mRNA levels after 72 h by 238%. IGF-I (6.5 nM) caused a 64% inhibition of 8-Br-cAMP-stimulated GH mRNA levels and a similar inhibition of GH secretion. This inhibition was time and dose dependent, with maximal (71%) suppression of cAMP-induced GH achieved with 13 nM IGF-I after 72 h. Forskolin (1 microM), a stimulator of adenylate cyclase, stimulated GH secretion (198%) which was inhibited by IGF-I by 42%. 12-O-Tetradecanoylphorbol 13-acetate, (a phorbol ester; 50 nM), a potent activator of protein kinase C, strongly stimulated GH secretion (347%), which was similarly suppressed by IGF-I by 51%. The suppressive action of IGF-I on somatotroph gene expression is unimpaired by direct activation of both cAMP and protein kinase C, suggesting that IGF-I acts upon the GH gene by a mechanism that is not altered by these second messengers. The negative feedback inhibition of physiological concentrations of IGF-I on GH, therefore, appears to override the potent stimulation of GH by these intracellular messengers.
...
PMID:Insulin-like growth factor I action on rat anterior pituitary cells: effects of intracellular messengers on growth hormone secretion and messenger ribonucleic acid levels. 367 37

Normal postnatal somatic growth becomes progressively dependent on GH with time. In contrast to other hormones, GH is the only hormone known to produce a dose-dependent stimulation of postnatal growth. Most of the effects attributed to GH action appear to be the result of a direct effect of GH on cells in different peripheral tissues, including cartilage. In addition to the growth-stimulating effect, GH has the intrinsic properties of being able to exert both insulin-like and insulin-antagonistic effects in adipose tissue and skeletal muscle. These two apparently antagonistic effects seem to be explained by the stage of responsiveness of the target cells to GH, which is determined by the previous influence of endogenous GH. An inhibition of adenylate cyclase with a concomitant decrease in intracellular cAMP might be an important early cellular event in the course of GH action, but it is not known whether or how this change in nucleotide metabolism relates to the various expressed effects of the hormone. The recognition that GH directly interacts with chondrocytes in cartilage suggests that alterations in the concentration of circulating somatomedins cannot be the only factor regulating skeletal growth. The recent discovery by Green and coworkers (42) demonstrating that GH specifically stimulates the differentiation of cloned preadipose cells and myoblasts in tissue culture may be a major breakthrough in the understanding of the mechanism of action of the growth-promoting effect of GH. Green (42) has proposed that GH directly stimulates terminal differentiation of cells in many different tissues including epiphyseal plate cartilage. The finding that GH binds specifically to cells in the resting cell zone but not to differentiated chondrocytes in the growth plate suggests that prechondrocytes in the growth plate are the target cells for GH action. If it is correct that GH directly stimulates the differentiation of prechondrocytes, we suggest that, during the process of chondrocyte differentiation in the growth plate, the genes that code for growth factors of the somatomedin class, such as IGF-I, are expressed. As a consequence, the clonal expansion of the chondrocytes in the proliferative zone of the growth plate that occurs in vivo during the process of normal growth is the result of this local production of growth factors.
...
PMID:Mode of action of pituitary growth hormone on target cells. 388 78

In previous studies it was shown that bovine GH (bGH) and glucagon, when individually added to primary rat hepatocyte cultures, modestly stimulated IGF-I mRNA levels 1.8- to 2.5-fold, but when combined, synergized to stimulate IGF-I mRNA levels by 10- to 12-fold. In the present study we have explored further the mechanism of this effect in primary rat hepatocyte cultures. Like glucagon, the addition of 3-isobutyl-1-methylxanthine (100 microM) or (Bu)2cAMP (150 microM) augmented IGF-I mRNA levels 1.8- to 2.0-fold, but when combined with bGH (50 ng/ml), they augmented levels up to 12-fold. The half-life of IGF-I mRNA, determined by incubating hepatocytes with actinomycin-D was 12 h. Although bGH did not affect the decay rate, glucagon (100 ng/ml) or (Bu)2cAMP (100 microM) reduced the rate of loss by about 70%. 4 beta-Phorbol 12 beta-myristate 13 alpha-acetate minimally stimulated IGF-I mRNA levels 1.2- to 1.4-fold, but displayed no synergism when added with bGH, glucagon, or (Bu)2cAMP. The stimulatory effect of bGH plus glucagon was inhibited 80% after preincubation with 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (10 microM) for 24 h. The addition of staurosporine, sphingosine, or H-7 [1-(5-isoquinolinyl sulfonyl)2-methyl piperazine] inhibited the stimulatory effect of bGH plus glucagon on hepatocyte IGF-I mRNA by 80%, 90%, and 85%, respectively. Preincubation with cycloheximide (10 micrograms/ml) blocked the synergistic effect of bGH plus either glucagon or (Bu)2cAMP by 65-80%. The effect of glucagon, mediated via the activation of adenylate cyclase, involves in part the posttranscriptional stabilization of IGF-I mRNA levels. The effect of GH, mediated in part by the activation of protein kinase-C, appears to be at the level of transcription. The synergistic augmentation of hepatocyte IGF-I mRNA levels by GH and glucagon involves the activation of PKA and PKC, but also appears to require the synthesis of one or more protein(s).
...
PMID:The augmentation of insulin-like growth factor-I messenger ribonucleic acid in cultured rat hepatocytes: activation of protein kinase-A and -C is necessary, but not sufficient. 750 34


1 2 Next >>

---