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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transfection of mouse Y1 adrenal tumor cells with DNA encoding mutant type I regulatory subunit generated stable transformants in which the basal activity of cAMP-dependent protein kinase was repressed. As expected, steroidogenesis in these kinase-deficient cells was no longer stimulated by corticotropin or cAMP analogues, and the expression of three cAMP-regulated genes (ornithine decarboxylase, urokinase-type plasminogen activator, and P450 side-chain cleavage) could no longer be induced. However, in addition to the loss of hormone responsiveness, the basal level of steroidogenesis and the constitutive expression of these cAMP-inducible genes was also repressed in kinase-defective mutant clones. To verify that functional cA-PK would revert this repressed phenotype, we transfected a cA-PK defective subclone of Y1 cells, Kin 8, with DNA encoding the C alpha and C beta subunits of cAMP-dependent protein kinase. Basal levels of steroid production were restored to normal in stable transformants, and the elevation of kinase activity following induction of the C-subunit expression vectors elicited a steroidogenic response. Gene transcription was also shown to be regulated by either C alpha or C beta as measured by the induction of plasminogen activator and ornithine decarboxylase mRNA levels and transcription rates. The dominant role played by cAMP-dependent protein kinase in these adrenal cells was demonstrated by experiments showing the regulation of ornithine decarboxylase gene expression by protein kinase C requires basal cAMP-dependent protein kinase activity.
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PMID:Cyclic AMP-dependent protein kinase controls basal gene activity and steroidogenesis in Y1 adrenal tumor cells. 156 25

We have reported previously that expression of the human apolipoprotein E (apoE) gene in mouse Y1 adrenocortical cells suppresses basal and adrenocorticotropin (ACTH)-stimulated steroidogenesis. To understand the mechanism of this suppression, we have examined the integrity of cAMP regulated events required for adrenal steroidogenesis. Both acute and chronic responses to ACTH or cAMP are suppressed in Y1 cells which express apoE (Y1-E cells) as compared with parental Y1 cells. Acute morphologic changes in response to cAMP and acute induction of steroidogenesis by cAMP are suppressed in the Y1-E cell lines. Constitutive expression of P450-cholesterol side chain cleavage enzyme mRNA, the rate-limiting enzyme in steroid hormone synthesis, is reduced up to 11-fold in the Y1-E cell lines. The level of mRNA encoding P450-cholesterol side chain cleavage correlates directly with the reduction in basal steroid production observed in the individual Y1-E cell lines. Expression of P450-11 beta-hydroxylase mRNA, although readily detectable in Y1 parent cells, is absent or reduced in the Y1-E cell lines. Inhibition of cAMP-regulated gene expression is not restricted to genes required for steroid synthesis, since cAMP induction of ornithine decarboxylase mRNA is also inhibited in the Y1-E cell lines. These data indicate that suppression of steroidogenesis in Y1-E cells is due, at least in part, to inhibition of cAMP-regulated gene expression. These effects are not due to a defective cAMP-dependent protein kinase, since kinase activity in vitro and activation in vivo are unaltered in the Y1-E cell lines. These results suggest that expression of apoE in Y1 cells blocks cAMP-mediated signal transduction at a point distal to activation of cAMP-dependent protein kinase.
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PMID:Suppression of cAMP-mediated signal transduction in mouse adrenocortical cells which express apolipoprotein E. 165 49

Results from a number of studies suggest a role for endogenous opioids in the regulation of lung development and function. Although it is not known which opioid peptides are involved in these processes, accumulated evidence suggests a prominent role for beta-endorphin (BE). Our study examines the effect of BE on lung ornithine decarboxylase (ODC) activity in preweanling rats. ODC catalyzes the rate-limiting step in the synthesis of the polyamines spermidine and spermine, key regulators of cell growth, multiplication, and differentiation. Central (but not peripheral) administration of BE reduced lung ODC activity by as much as 80% in the 6-d-old rat. Significant decreases in ODC activity were seen at doses of BE as low as 0.5 micrograms/g brain wt. In contrast to the reductions in ODC activity, plasma levels of corticosterone in animals administered BE were approximately five times higher than those seen in control animals. BE's actions on ODC activity and plasma corticosterone levels were prevented by naloxone or naltrexone, indicating that both responses are mediated by opioid receptors. Studies of ODC kinetics showed a profound reduction in Vmax (70% below control values), but no change in Km. The effect was observed only during the first 2 wk of postnatal age, a period of time in lung maturation that is characterized by active alveolarization. Because changes in ODC levels during early postnatal life are associated with perturbations in tissue growth and/or function, the data suggest that CNS BE may influence lung maturation through an indirect action that may involve glucocorticoids.
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PMID:Effect of central administration of beta-endorphin on lung ornithine decarboxylase activity in developing rats. 201 56

We have previously shown that central administration of beta-endorphin results in a reduction of ornithine decarboxylase activity. Ornithine decarboxylase catalyses the rate-limiting step in the biosynthesis of the polyamines putrescine, spermidine and spermine, thought to modulate nucleic acid synthesis. The present study examines the effects of intracisternal injection of beta-endorphin on brain and liver DNA synthesis in preweanling rats. In six-day-old rats, beta-endorphin (0.75 micrograms/g brain wt) produced approximately a 70% inhibition in brain and liver DNA synthesis 1 h after injection, and values were still subnormal in both tissues 10 h later. Subcutaneous administration of beta-endorphin did not alter liver DNA synthesis. Thus, it is most likely that the suppressed liver DNA synthesis observed in animals given beta-endorphin intracisternally is mediated by central mechanisms. Co-administration of naloxone plus beta-endorphin intracisternally prevented the response, indicating an opioid receptor-mediated phenomenon. Naloxone alone caused small but significant increases in brain and liver DNA synthesis, suggesting a tonic influence on tissue DNA by endogenous opioids in the CNS. Acute inhibition of ornithine decarboxylase activity by alpha-difluoromethylornithine did not alter DNA synthesis, indicating that the decreases in DNA synthesis induced by beta-endorphin are unrelated to the ornithine decarboxylase/polyamine system. The effect appears to be restricted to early development as no significant changes in DNA synthesis were obtained in 20-day-old animals. The results from these studies indicate that CNS beta-endorphin has the ability to influence DNA synthesis in central as well as in peripheral tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of central administration of beta-endorphin on brain and liver DNA synthesis in preweanling rats. 205 54

Recently, our laboratory has reported that central administration of beta-endorphin to rat pups decreases hepatic and renal ornithine decarboxylase activity, a sensitive biochemical index of tissue metabolic activity. Since these organs are the major sites of insulin catabolism, it seemed possible that the plasma levels of this hormone could be altered by changes in central nervous system (CNS) beta-endorphin levels. In the current study we tested this hypothesis by administering beta-endorphin to rat pups intracisternally (ic), followed by insulin sc, and then analyzing for plasma levels of insulin and glucose at various times after the second injection. We found that the apparent biological half-life of administered insulin markedly increased in 6-day-old rats pretreated with beta-endorphin ic. Similarly, this neuropeptide prolonged the half-life of endogenous insulin, as indicated by a small but significant increase in the plasma levels of this hormone in animals given only beta-endorphin. As expected, hypoglycemia in rats injected with beta-endorphin and insulin was more pronounced than in animals given insulin alone. Naloxone administered ic reversed both actions of beta-endorphin, indicating the involvement of opioid receptors in the response. beta-Endorphin also altered insulin and glucose plasma levels in 2-, 10-, and 18-day-old rats, but there were no effects in 30-day-old animals at any of the doses used in these studies. Peripheral administration of beta-endorphin had no effect, indicating that CNS beta-endorphin's influences on insulin and glucose metabolism occur through brain-based mechanisms. The results from these studies suggest that CNS beta-endorphin may be an important modulator of insulin and glucose metabolism in preweanling rats. In as much as insulin is a major regulator of somatic growth, our findings further suggest that CNS beta-endorphin may have a major role in the control of growth during early postnatal development by influencing insulin homeostasis.
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PMID:Regulation of insulin and glucose plasma levels by central nervous system beta-endorphin in preweanling rats. 252 2

Bovine adrenocortical cells of fasciculo-reticulata origin in primary culture actively accumulate polyamines from the extracellular medium in an energy-dependent process. At low extracellular concentration (e.g., 1 microM putrescine), the transport system resulted in a several-hundred-fold concentration of polyamine in the cellular compartment within 1-2 h of incubation. Putrescine uptake appeared to be the sum of a sodium-dependent, saturable process, with an apparent Km of about 10 microM and of a non-saturable, sodium-independent component. By contrast, spermine was taken up by the cells mostly in a sodium-independent manner. Cross-competition experiments suggested that both polyamines were at least partly transported by the same system. Using specific corresponding probes, it was shown that the polyamine uptake was independent of the amino acid transport systems of the A, L and N types known in a number of cell systems. Adrenocortical cell polyamine content is known to be modulated by adrenocorticotropin through induction of ornithine decarboxylase activity. The existence of a specific uptake system in these cells opens the possibility of a more rapid pathway for the regulation of cellular polyamine levels. It remains to be examined whether this polyamine transport system is under hormonal control, and whether this can support the suggestion that polyamines may represent a form of intracellular messengers in the mechanism of hormone action.
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PMID:Polyamine uptake by bovine adrenocortical cells. 299 May 82

The activity of N1-acetyltransferase was increased in the dissected adrenal cortex of the rat following a single administration of spermidine. The activity was maximal 6-8 h after the onset of treatment. The increase in enzyme activity was abolished when the rats were given cycloheximide 2 h after spermidine; this suggests that increased activity results from an augmentation in the synthesis of the enzyme. Adrenocortical spermidine N1-acetyltransferase was also induced by carbamylcholine, 2-deoxyglucose, apomorphine and piribedil, drugs that are known to cause induction of ornithine decarboxylase in that organ. Hypophysectomized rats showed reduced activity of spermidine N1-acetyltransferase when compared to sham-operated controls, and carbamylcholine no longer elicited an increase in enzyme activity in such animals. Adrenocortical spermidine N1-acetyltransferase activity of hypophysectomized rats is induced by corticotropin (ACTH). These results suggest a hormonal control over the activity of the enzyme in the adrenal cortex with ACTH acting as a mediator.
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PMID:Increased activity of spermidine N1-acetyltransferase in the adrenal cortex of rats following administration of exogenous spermidine, carbamylcholine, 2-deoxyglucose and dopamine agonists. 301 42

Our laboratory has demonstrated recently that administration of beta-endorphin to rat pups results in profound changes in the levels of the growth-related enzyme ornithine decarboxylase (ODC) in both brain and peripheral tissues. These findings are consistent with accumulated evidence indicating that, in addition to their analgesic and behavioral effects in the adult, endogenous opioid peptides and opioid receptors may be involved as mediators of tissue growth and function in the neonate. This study examines the effects of N alpha-acetyl-beta-endorphin on tissue ODC activity to determine whether post-translational acetylation of beta-endorphin at the N alpha-terminus affects its capability to alter ODC activity and, consequently, tissue development. Intracisternal administration of N alpha-acetyl-beta-endorphin evoked profound increases in brain ODC activity in 6- and 9-day-old rats, whereas normal ODC levels were observed in 25-day-old animals and in adult rats. Centrally administered N alpha-acetyl-beta-endorphin had no effect on ODC in peripheral tissues. In contrast, s.c. administration of this peptide to 6-day-old animals resulted in marked increases in ODC activity in the heart, liver and brain. Naloxone inhibited the stimulatory actions of N alpha-acetyl-beta-endorphin on brain ODC completely, indicating the involvement of opioid receptors in that process. On the other hand, the increases in liver ODC were not prevented by naloxone, suggesting that these effects are not mediated through opioid-sensitive structures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:N alpha-acetyl-beta-endorphin stimulates ornithine decarboxylase activity in preweanling rat pups: opioid- and non-opioid-mediated mechanisms. 355 81

Transglutaminase (TGase; R-glutaminyl-peptide:amine gamma-glutamyltransferase, EC 2.3.2.13) and ornithine decarboxylase (ODCase; L-ornithine carboxy-lyase, EC 4.1.1.17) activities were measured after the addition of retinoid analogs to Chinese hamster ovary (CHO) cells released from quiescence and Cloudman S91 (CCL 53.1) mouse melanoma cells stimulated to differentiate with alpha-melanocyte-stimulating hormone (MSH, melanotropin). In both cell culture lines, we detected a biphasic increase in TGase activity and a single peak of ODCase activity within 7 hr after release or stimulation. Retinoid analogs altered the expression of the initial TGase peak in both CHO and melanoma cells. Retinol increased the activity of TGase 1 hr after release in CHO cells, and the activity remained elevated until hr 4. A broad peak of TGase activity also occurred after the addition of alpha-difluoromethylornithine, an irreversible inhibitor of ODCase, and after addition of alpha-difluoromethylornithine plus retinol. In mouse melanoma cells, retinoic acid plus MSH markedly enhanced the activity of the initial TGase peak compared to MSH alone. Retinoic acid alone also increased TGase activity biphasically in these cells without the addition of MSH. These studies suggest that retinoid effects that increase TGase activity may alter the ODCase expression in proliferation and differentiation.
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PMID:Retinoids increase transglutaminase activity and inhibit ornithine decarboxylase activity in Chinese hamster ovary cells and in melanoma cells stimulated to differentiate. 612 41

In Y1 adrenocortical tumor cells, corticotropin (ACTH), cyclic AMP, and 8-bromoadenosine 3',5'-monophosphate (8BrcAMP) stimulated ornithine decarboxylase activity (L-ornithine carboxy-lyase, EC 4.1.1.17) and steroidogenesis. The concentrations required for half-maximal activation of ornithine decarboxylase were 60 pM for ACTH and 1 mM for 8BrcAMP; the concentrations required for half-maximal activation of steroidogenesis were 50 pM for ACTH and 0.2 mM for 8BrcAMP. Ornithine decarboxylase activity increased 1.5 hr after the addition of these agents, reached a maximum between 4 and 6 hr, and then declined. Mutant clones with impaired ACTH-responsive adenylate cyclase systems [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]did not respond to ACTH with increased ornithine decarboxylase activity, but they responded normally to added cyclic AMP. These results indicate that adenylate cyclase and cyclic AMP are necessary for the stimulation of ornithine decarboxylase activity by ACTH. In a series of Y1(Kin) mutants with altered cyclic AMP-dependent protein kinase activities (ATP:protein phosphotransferase, EC 2.7.1.37), the effects of ACTH on ornithine decarboxylase also were attenuated. These findings suggest that cyclic AMP-dependent protein kinase also plays a necessary role in the stimulation of ornithine decarboxylase activity by ACTH. The effects of ACTH on ornithine decarboxylase in the Kin mutants, however, were quantitatively different from the effects on steroidogenesis and did not closely reflect the degree of defect in cyclic AMP-dependent protein kinase activity. These differences suggest that the pathways of ACTH action leading to stimulation of steroidogenesis and ornithine decarboxylase activity diverge subsequent to activation of the protein kinase.
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PMID:Regulation of ornithine decarboxylase activity by corticotropin in adrenocortical tumor cell clones: roles of cyclic AMP and cyclic AMP-dependent protein kinase. 624 65


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