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Prolonged inhibition of presynaptic catecholamine synthesis with alpha-methyl-para-tyrosine attenuates the circadian rhythm of human TSH secretion.

Abstract

OBJECTIVE

Originating from the pituitary gland, TSH secretion is regulated predominantly by thyroid-releasing hormone (TRH) neurons located in the hypothalamus. Norepinephrine and dopamine have important effects in modulation of TSH secretion. An inhibitor of catecholamine synthesis, alpha-methyl-para-tyrosine (AMPT) has been used in several studies of the regulation of human TSH secretion. The short-term effects (<8 hours) of low doses of AMPT include stimulation of pituitary TSH secretion by selective lowering of brain dopamine levels. After prolonged administration of AMPT (>24 hours), theoretically both dopamine and norepinephrine levels are lowered significantly in the brain, although this has not been reported previously.

METHODS

Nine subjects (five women and four men) received a total of five 1-g doses of AMPT or five 50-mg doses of promethazine (active placebo) over 28 hours in a randomized, double-blind, placebo-controlled crossover design in which the active and control tests were separated by 4-6 weeks. Blood samples were obtained over 24 hours (18 time points) on day 2 of each condition.

RESULTS

Changes in prolactin secretion and 6-hydroxymelatonin sulfate excretion indirectly showed the effects of AMPT on dopamine and norepinephrine. The typical circadian rhythm of TSH secretion was blunted by AMPT throughout the night; at ten time points, the difference between the two groups was statistically significant (P <.01). The long-term effects of repeated doses of AMPT were inhibition of TSH secretion and significant attenuation of the circadian rhythm of TSH. Additionally, AMPT induced low norepinephrine levels, which counteracted the stimulatory effect of low dopamine levels on TSH.

CONCLUSION

Through its inhibitory effect on TRH, norepinephrine appeared to be involved in the regulation of TSH.

Authors+Show Affiliations

,

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Columbia University, New York, New York 10032, USA.

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Source

MeSH

Adult
Catecholamines
Circadian Rhythm
Cross-Over Studies
Dopamine
Double-Blind Method
Enzyme Inhibitors
Epinephrine
Female
Humans
Male
Melatonin
Placebos
Prolactin
Promethazine
Synapses
Thyrotropin
Tyrosine 3-Monooxygenase
alpha-Methyltyrosine

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11390253

Citation

Zimmermann, R C., et al. "Prolonged Inhibition of Presynaptic Catecholamine Synthesis With Alpha-methyl-para-tyrosine Attenuates the Circadian Rhythm of Human TSH Secretion." Journal of the Society for Gynecologic Investigation, vol. 8, no. 3, 2001, pp. 174-8.
Zimmermann RC, Krahn LE, Klee GG, et al. Prolonged inhibition of presynaptic catecholamine synthesis with alpha-methyl-para-tyrosine attenuates the circadian rhythm of human TSH secretion. J Soc Gynecol Investig. 2001;8(3):174-8.
Zimmermann, R. C., Krahn, L. E., Klee, G. G., Ditkoff, E. C., Ory, S. J., & Sauer, M. V. (2001). Prolonged inhibition of presynaptic catecholamine synthesis with alpha-methyl-para-tyrosine attenuates the circadian rhythm of human TSH secretion. Journal of the Society for Gynecologic Investigation, 8(3), pp. 174-8.
Zimmermann RC, et al. Prolonged Inhibition of Presynaptic Catecholamine Synthesis With Alpha-methyl-para-tyrosine Attenuates the Circadian Rhythm of Human TSH Secretion. J Soc Gynecol Investig. 2001;8(3):174-8. PubMed PMID: 11390253.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prolonged inhibition of presynaptic catecholamine synthesis with alpha-methyl-para-tyrosine attenuates the circadian rhythm of human TSH secretion. AU - Zimmermann,R C, AU - Krahn,L E, AU - Klee,G G, AU - Ditkoff,E C, AU - Ory,S J, AU - Sauer,M V, PY - 2001/6/8/pubmed PY - 2001/7/20/medline PY - 2001/6/8/entrez SP - 174 EP - 8 JF - Journal of the Society for Gynecologic Investigation JO - J. Soc. Gynecol. Investig. VL - 8 IS - 3 N2 - OBJECTIVE: Originating from the pituitary gland, TSH secretion is regulated predominantly by thyroid-releasing hormone (TRH) neurons located in the hypothalamus. Norepinephrine and dopamine have important effects in modulation of TSH secretion. An inhibitor of catecholamine synthesis, alpha-methyl-para-tyrosine (AMPT) has been used in several studies of the regulation of human TSH secretion. The short-term effects (<8 hours) of low doses of AMPT include stimulation of pituitary TSH secretion by selective lowering of brain dopamine levels. After prolonged administration of AMPT (>24 hours), theoretically both dopamine and norepinephrine levels are lowered significantly in the brain, although this has not been reported previously. METHODS: Nine subjects (five women and four men) received a total of five 1-g doses of AMPT or five 50-mg doses of promethazine (active placebo) over 28 hours in a randomized, double-blind, placebo-controlled crossover design in which the active and control tests were separated by 4-6 weeks. Blood samples were obtained over 24 hours (18 time points) on day 2 of each condition. RESULTS: Changes in prolactin secretion and 6-hydroxymelatonin sulfate excretion indirectly showed the effects of AMPT on dopamine and norepinephrine. The typical circadian rhythm of TSH secretion was blunted by AMPT throughout the night; at ten time points, the difference between the two groups was statistically significant (P <.01). The long-term effects of repeated doses of AMPT were inhibition of TSH secretion and significant attenuation of the circadian rhythm of TSH. Additionally, AMPT induced low norepinephrine levels, which counteracted the stimulatory effect of low dopamine levels on TSH. CONCLUSION: Through its inhibitory effect on TRH, norepinephrine appeared to be involved in the regulation of TSH. SN - 1071-5576 UR - https://www.unboundmedicine.com/medline/citation/11390253/Prolonged_inhibition_of_presynaptic_catecholamine_synthesis_with_alpha_methyl_para_tyrosine_attenuates_the_circadian_rhythm_of_human_TSH_secretion_ L2 - https://www.lens.org/lens/search?q=citation_id:11390253 DB - PRIME DP - Unbound Medicine ER -