This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zimmermann, R. C. Articles by Sauer, M. V. Search for Related Content PubMed PubMed Citation Articles by Zimmermann, R. C. Articles by Krahn, L. E. Articles by Klee, G. G. Articles by Ditkoff, E. C. Articles by Ory, S. J. Articles by Sauer, M. V. Social Bookmarking                   What's this?

Prolonged Inhibition of Presynaptic Catecholamine Synthesis With -Methyl-Para-Tyrosine Attenuates the Circadian Rhythm of Human TSH Secretion

Lois E. Krahn, MD

George G. Klee, MD

Edward C. Ditkoff, MD

Steven J. Ory, MD

Mark V. Sauer, MD

Departments of Obstetrics and Gynecology, Division of Reproductive Endocrinology, and Psychiatry, Columbia University, New York, New York; Division of Adult Psychiatry and Sleep Disorders Center, Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota; Margate, Florida

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, -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.

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

Key Words: AMPT • circadian rhythm • melatonin • norepinephrine • prolactin • thyrotropin

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?