Summary
-
1.
PhenylethanolamineN-methyltransferase (PNMT) is regulated by glucocorticoid hormones. This study investigates the ability of glucocorticoids to modulate transcription of the rat PNMT genein vivo andin vitro.
-
2.
In the adrenal glands of hypophysectomized (HPX'd) rats, the synthetic glucocorticoid dexamethasone (DEX) stimulates production of PNMT mRNA. Quantitative hybridization reveals that the levels of PNMT mRNA increase approximately threefold in total and poly(A)+ RNA after 4 days of DEX treatment of HPX'd rats, a level which is maximal for this treatment.
-
3.
ACTH, the hormonal stimulus of glucocorticoid biosynthesis in the adrenal cortex, enhances PNMT mRNA production to levels comparable to that achieved with DEX in this system. The steroid responsiveness of PNMT message production is specific for glucocorticoids. DEX also increases PNMT mRNA in the brain stem, although the magnitude and speed of response are lower than observed in the adrenal gland.
-
4.
Additional confirmation of the inductive ability of glucocorticoids is demonstrated by the increase in PNMT immunoprecipitated following translationin vitro of adrenal RNAs from DEX-treated rats. Furthermore, the PNMT mRNA signal obtained byin situ hybridization histochemistry in adrenal sections and in primary cultures of dispersed rat adrenal medullae reveals that DEX effects on PNMT mRNA can be elicited bothin vivo andin vitro.
-
5.
Specifically, glucocorticoids exert their effects on expression of PNMT mRNA by elevating the rate of PNMT gene transcription: a 2.3-fold increase in PNMT transcription persists for 18 hr following DEX treatment of HPX'd rats. In summary, this study establishes that glucocorticoids directly and rapidly stimulate transcription of the rat PNMT gene.
Similar content being viewed by others
References
Aviv, H., and Leder, P. (1972). Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose.Proc. Natl. Acad. Sci. USA 691408–1412.
Ballester, R., and Rosen, O. M. (1985). Fate of immunorprecipitable protein kinase C in GH3 cells treated with phorbol 12-myristate 13-acetate.J. Biol. Chem. 26015194–15199.
Baetge, E. E., Kaplan, B. B., Reis, D. J., and Joh, T. H. (1981). Translation of tyrosine hydroxylase from poly(A) mRNA in pheochromocytoma cells is enhanced by dexamethasone.Proc. Natl. Acad. Sci. USA 781269–1273.
Baetge, E. E., Suh, Y. H., and Joh, T. H. (1986). Complete nucleotide and deduced amino acid sequence of bovine phenylethanolamine N-methyltransferase: Sequence homology with rat tyrosine hydroxylase.Proc. Natl. Acad. Sci. USA 835454–5458.
Batter, D. K., D'Mello, S. R., Turzai, L. M., Hughes, H. B., III, Gioio, A. E., and Kaplan, B. B. (1988). The complete nucleotide sequence and structure of the gene encoding bovine phenylethanolamine N-methyltransferase.J. Neurosci. Res. 19367–376.
Berenbeim, D. M., Wong, D. M., Masover, S. J., and Ciaranello, R. D. (1979). Regulation of the synthesis and degradation of rat adrenal phenylethanolamine N-methyltransferase. III. Stabilization of the enzyme against thermal and tryptic degradation by S-adenosylmethionine.Mol. Pharmacol. 16482–490.
Black, I. B., Chikaraishi, D. M., and Lewis, E. J. (1985). Trans-synaptic increase in RNA coding for tyrosine hydroxylase in rat sympathetic ganglion.Brain Res. 339151–153.
Bohn, M. C. (1983). Role of glucocorticoids in expression and development of phenylethanolamine N-methyltransferase (PNMT) in cells derived from the neural crest. A review.Psychoneuroendocrinology 8381–390.
Bohn, M. C., Bloom, E., Goldstein, M., and Black, I. B. (1982). Glucocorticoid regulation of phenylethanolamine N-methyltransferase (PNMT) in organ culture of superior cervical ganglia.Dev. Biol. 105130–136.
Bohn, M. C., Goldstein, M., and Black, I. B. (1982b). Expression of phenylethanolamine N-methyltransferase in rat sympathetic ganglia and extra-adrenal chromaffin tissues.Dev. Biol. 89299–308.
Carroll, J. M., Evinger, M. J., Goodman, H. M., and Joh, T. H. (1991). Differential and coordinate regulation of TH and PNMT mRNAs in chromaffin cell cultures by second messenger system activation and steroid treatment.J. Mol. Neurosci. 375–83.
Ciaranello, R. D. (1978). Regulation of phenylethanolamine N-methyltransferase in rat adrenal glands. I. Regulation of enzyme synthesis and degradation by adrenal glucocorticoids.Mol. Pharmacol. 14478–489.
Diamond, D. J., and Goodman, H. M. (1985). Regulation of growth hormone messenger RNA synthesis by dexamethasone and triiodothyronine—transcriptional rate and mRNA stability in pituitary tumor cells.J. Mol. Biol. 18141–62.
Doupe, A. J., Landis, S. C., and Patterson, P. H. (1985). Environmental influences in development of neural crest derivatives: Glucocorticoids, growth factors and chromaffin cell plasticity.J. Neurosci. 52119–2142.
Eberwine, J. H., and Roberts, J. L. (1984). Glucocorticoid regulation of proopiomelanocortin gene transcription in the rat pituitary.J. Biol. Chem. 2592166–2170.
Eberwine, J. H., Jonassen, J., Evinger, M. J. Q., and Roberts, J. (1987). Complex transcriptional regulation by glucocorticoids and corticotropin-releasing hormone of proopiomelanocortin gene expression in rat pituitary cultures.DNA 2483–492.
Evinger, M. J., and Joh, T. H. (1989). Strain-specific differences in transcription of the gene for the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase.Mol. Brain Res. 5141–147.
Evinger, M. J., Park, D. H., Baetge, E. E., Reis, D. J., and Joh, T. H. (1986). Strain-specific differences in levels of the mRNA for the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase.Mol. Brain Res. 163–73.
Harfstrand, A., Fuxe, K., Cintra, A., Agnata, L. F., Zini, I., Wiksstrom, A.-C., Okret, S., Yu, Z.-Y., Goldstein, M., Steinbusch, H., Verhofstad, A., and Gustafsson, J. A. (1986). Glucocorticoid receptor immunoreactivity in monoaminergic neurons of rat brain.Proc. Natl. Acad. Sci. USA 839779–9783.
Jiang, W., Uht, R., and Bohn, M. C. (1989). Regulation of phenylethanolamine N-methyltransferase (PNMT) mRNA in the rat adrenal medulla by corticosterone.Int. J. Dev. Neurosci. 7513–520.
Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951). Protein measurement with the Folin phenol reagent.J. Biol. Chem. 193265–275.
Maniatis, T., Frisch, E. F., and Sambrook, J. (1982).Molecular Cloning—A Laboratory Manual, Cold Spring Harbor Laboratory Press; Cold Spring Harbor, NY, pp. 202–203.
Masover, S. J., Berenbeim, D. M., and Ciaranello, R. D. (1979). Regulation of the synthesis and degradation of rat adrenal phenylethanolamine N-methyltransferase. IV. Synergistic stabilization of the enzyme against thermal and tryptic degradation by S-adenosylmethionine and biogenic amine substrates.Mol. Pharmacol. 6491–503.
McKnight, G. S., and Palmiter, R. D. (1979). Transcriptional regulation of the ovalbumin and conalbumin genes by steroid hormones in the chick oviductJ. Biol. Chem. 2549050–9058.
Moore, K. E., and Phillipson, O. T. (1975) Effects of dexamethasone on phenylethanolamine N-methyltransferase and adrenaline in the brains and superior cervical ganglia of adult and neonatal rats.J. Neurochem. 25289–294.
Muller, T. H., and Unsicker, K. (1986). Nerve growth factor and dexamethasone modulate synthesis and storage of catecholamnines in cultured rat adrenal medullary cells: Dependence on postnatal age.J. Neurochem. 46516–524.
Murphy, D., Brickell, P. M., Latchman, D. S., Willison, K., and Rigby, P. W. J. (1983). Transcripts regulated during normal embryonic development and oncogenic transformation share a repetitive element.Cell 35865–875.
Pohorecky, L. A., and Wurtman, R. J. (1971). Adrenocortical control of epinephrine synthesis.Pharmacol. Rev. 231–35.
Ross, M. E., Evinger, M. J., Hyman, S. E., Carroll, J. M., Mucke, L., Comb, M., Reis, D. J., Joh, T. H., and Goodman, H. M. (1990). Identification of a functional glucocorticoid response element in the phenylethanolamine N-methyltransferase promoter using fusion genes introduced into chromaffin cells in primary culture.J. Neurosci. 10520–530.
Sabban, E., Goldstein, M., Bohn, M. C., and Black, I. B. (1982). Development of the adrenergic phenotype: Increase in adrenal messenger RNA encoding for phenylethanolamine N-methyltransferase.Proc. Natl. Acad. Sci. USA 794823–4827.
Stachowiak, M. K., Rigual, R. J., Lee, P. H. K., Viveros, O. H., and Hong, J. S. (1988). Regulation of tyrosine hydroxylase and phenylethanolamine N-methyltransferase mRNA levels in the sympathoadrenal system by the pituitary-adrenocortical axis.Mol. Brain Res. 3275–286.
Teitelman, G., Joh, T. H., Park, D., Brodsky, M., New, M., and Reis, D. J. (1982). Expression of the adrenergic phenotype in cultured fetal adrenal medullary cells: Role of intrinsic and extrinsic factors.Dev. Biol. 89450–459.
Thomas, P. S. (1980). Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose.Proc. Natl. Acad. Sci. USA 77 5201–5205.
Towle, A. C., Paivarinta, H., Evinger, M. J., and Joh, T. H. (1987). Genetic regulation of catecholamine enzyme synthesis in Fischer 344 and Buffalo rat adrenals.Soc. Neurosci. Abstr. 13478.
Unsicker, K., Krisch, B., Otten, U., and Thoenen, H. (1978). Nerve growth factor-induced fiber outgrowth from isolated rat adrenal chromaffin cells: Impairment by glucocorticoids.Proc. Natl. Acad. Sci. USA 753498–3502.
Wong, D. L., Zager, E. L., and Ciaranello, R. D. (1982). Effects of hypophysectomy and dexamethasone administration on central and peripheral S-adenosylmethionine.J. Neurosci. 2758–764.
Wurtman, R. J., and Axelrod, J. (1965). Adrenaline aynthesis: Control by the pituitary gland and adrenal glucocorticoids.Science 1501464–1465.
Wurtman, R. J., and Axelrod, J. (1966). Control of enzymatic synthesis of adrenaline in the adrenal medulla by adrenalcortical steroids.J. Biol. Chem. 2412301–2305.
Wurtman, R. J., Pohorecky, L. A., and Baliga, B. (1972). Adrenocortical control of the biosynthesis of epinephrine and proteins in the adrenal medulla.Pharmacol. Rev. 24411–426.
Yamamoto, K. R. (1985). Steroid receptor regulated transcription of specific genes and gene networks.Annu. Rev. Genet. 19209–252.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Evinger, M.J., Towle, A.C., Park, D.H. et al. Glucocorticoids stimulate transcription of the rat phenylethanolamineN-methyltransferase (PNMT) genein vivo andin vitro . Cell Mol Neurobiol 12, 193–215 (1992). https://doi.org/10.1007/BF00712926
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00712926