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Dose-Response Studies With Protirelin

James C. Garbutt, MD; James P. Mayo, MD; Karley Y. Little, MD; Gregory M. Gillette, MD; George A. Mason, PhD; Bess Dew, RN; Arthur J. Prange Jr, MD
Arch Gen Psychiatry. 1994;51(11):875-883. doi:10.1001/archpsyc.1994.03950110035006.
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Background:  A reduced thyrotropin (TSH) response to thyrotropin-releasing hormone (protirelin [TRH]) has been found consistently in a portion of patients with major depression. One hypothesis to explain this observation is that pituitary TRH receptors are downregulated in major depression. One prediction stemming from this hypothesis is that prolactin (PRL) as well as TSH responses to TRH should be attenuated. To adequately test the pattern of protirelin-induced TSH and PRL responses with a protirelin doseresponse design is necessary.

Methods:  Four doses of protirelin (25, 100, 500, and 800 μg) were infused in an ascending schedule at intervals of 3 to 7 days in patients with major depression and in control subjects. Seven women and six men with major depression were compared with ageand gender-matched controls (five women and seven men). The TSH and PRL responses were measured at regular intervals following each dose of protirelin.

Results:  No significant group differences in baseline levels of thyroid hormones or cortisol were present. Depressed men exhibited significant reductions in both TSH and PRL responses to protirelin across all doses compared with control men. Depressed women exhibited significant reductions in TSH responses but not in PRL responses compared with control women.

Conclusions:  The findings that men with major depression exhibit reductions in both protirelin-induced TSH and PRL responses support the hypothesis that TRH receptors are downregulated in depression. The findings in women are less clear and may represent the greater variance in the protirelin-induced PRL responses found in women.

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