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Dopaminergic Control of Circadian and Pulsatile Pituitary Thyrotropin Release in Women^*

W. G. ROSSMANITH, J. F. MORTOLA, G. A. LAUGHLIN and S. S. C. YEN

Department of Reproductive Medicine, School of Medicine (T-002), and the General Clinical Research Center, University of California-San Diego La Jolla, California 92093

Address all correspondence and requests for reprints to: Dr. S. S. C. Yen, Department of Reproductive Medicine (T-002), University of California-San Diego, La Jolla, California 92093.

Dopamine (DA) inhibits pituitary TSH release, but its role as a regulator of circadian and pulsatile TSH secretion is not clear. Accordingly, we studied the 24-h TSH secretory patterns in seven normal women in the early follicular phase of their cycles before and during DA receptor blockade by metoclopramide (MCP). Serum TSH was measured by a highly sensitive (0.05 mU/L) RIA at 15-min intervals for 48 h during sequential 24-h saline and 24-h MCP infusions (30 µg/kg·h). Sleep was confirmed by electroencephalogram between 2300–0700 h. All women had a nocturnal rise of TSH, independent of sleep, which began in the late afternoon and reached a peak (acrophase) after midnight during the saline infusion. This circadian periodicity was composed of a series of TSH pulses with greater magnitude and frequency during nocturnal hours. Infusion of MCP had no effect on pulse frequency, but the pulse amplitude increased (P < 0.05), especially at night. As a consequence, the circadian excursion of TSH, as assessed by cosinor function, was exaggerated. The mean acrophase amplitude and mesor levels increased (P < 0.05), but the nadir and acrophase times did not change. These findings suggest that DA is an inhibitor of TSH pulse amplitude throughout the 24-h biological clock. By inference, the neuroendocrine mechanism(s) that underlies the nocturnal increase in TSH secretion is not due to decreased dopaminergic inhibition.

^* This work was supported by NIH/NICHHD Research Center Grants HD-12303 and HD-21198, and in part by the UCSD General Clinical Research Center NIH/Division of Research Resources Grant RR-00827. This research was conducted in part by the Clayton Foundation for Research, California Division.

Research Fellow, recipient of German Research Foundation Grant Ro 657/1-2. Present address: Department of Obstetrics and Gynecology, University of Ulm, Prittwitzstrasse 43, D-7900 Ulm/D., West Germany.

Andrew Mellon Foundation Faculty Scholar.

Clayton Foundation Investigator.

Received January 27, 1988.

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