Developmental-Regulatory Aspects of Brain Tryptophan Hydroxylase
Several articles in this volume deal with the roles of serotonin and other neurohumoral substances in the regulation of neurogenesis. It should be emphasized that the maturation of the serotonergic system itself must also be subjected to regulation by a variety of biochemical events. In our laboratory, we are concerned with the developmental regulation of tryptophan hydroxylase (TPH), the enzyme that catalyzes the initial and probably rate-limiting step in the biosynthesis of serotonin from tryptophan. Two regulatory aspects are described in this article. One involves adrenal glucocorticoids as a regulatory factor for the enzyme during postnatal development of the brain. The other involves the activation of the enzyme by ATP-magnesium and its developmental relevance. Some of the unpublished experiments summarized here were conducted in collaboration with my energetic colleagues, Tom Lysz, Andy Towle, and Ralph F. Alderson. Their contribution to the overall work was no less important than mine.
KeywordsAdenosine Serotonin Dexamethasone Tryptophan Cytosol
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- 2.P.Y. Sze, Glucocorticoid regulation of the serotonergic system of the brain, Advan. Biochem. Psychopharm. 15: 251 (1976).Google Scholar
- 8.D. J. Ingle, The role of the adrenal cortex in homeostasis, Proc. Soc. Endocrinology 8: 23 (1952).Google Scholar
- 9.B. B. Brodie, J. I. Davies, S. Hynie, G. Krishna, and B. Weiss, Interrelationships of catecholamines with other endocrine systems, Pharmacol. Rev. 18: 273 (1966).Google Scholar
- 14.J. H. Exton, L. E. Mallette, L. S. Jefferson, E.H.A. Wong, and N. Friedmann, The hormonal control of hepatic gluconeogenesis, Recent Progr. Hormone Res. 26: 411 (1970).Google Scholar
- 15.A. M. Lefer and D. C. Sutfin, Cardiovascular effects of catecholamines in experimental adrenal insufficiency, Amer. J. Physiol. 206: 1151 (1964).Google Scholar
- 20.M. A. Brostrom, C. Kon, D. R. Olson, and B. McL. Breckenridge, Adenosine 3′,5′-monophosphate in glial cells treated with glucocorticoids, Mol. Pharmacol. 10: 711 (1974).Google Scholar
- 22.A. C. Towle and P. Y. Sze, Binding of corticosterone to synaptic plasma membrane from rat brain, Soc. Neurosci. Abst. 4: 356 (1978).Google Scholar
- 24.A. C. Towle, P. Y. Sze, and J. M. Lauder, Cytosol glucocorticoid receptors in monoaminergic cell groups, Trans. Amer. Soc. Neurochem. 10: 199 (1979).Google Scholar
- 26.D. M. Kuhn, R. L. Vogel, and W. Lovenberg, Activation of tryptophan hydroxylase by ATP and Mg+2, Trans. Amer. Soc. Neurochem. 9: 184 (1978).Google Scholar
- 27.M. Haman, S. Bourgoin, F. Hery, and G. Simonet, Activation of tryptophan hydroxylase by adenosine triphosphate, magnesium and calcium, Mol. Pharmacol. 14: 99 (1978).Google Scholar
- 29.D. H. Park, T. H. Joh, S. Chiang, and D. J. Reis, Properties and activation of tryptophan hydroxylase from rat brain, Trans. Amer. Soc. Neurochem. 10: 182 (1979).Google Scholar