Thyrotropin: α- and β-Subunits of Thyrotropin, and Prolactin Responses to Four-Hour Constant Infusions of Thyrotropin-Releasing Hormone in Normal Subjects and Patients with Pituitary-Thyroid Disorders*

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Abstract
TRH was administered as a 4-h constant rate iv infusion (0.4 µg/min) to eight healthy euthyroid volunteers, three euthyroidfemales on estrogen, eight hyperthyroid patients, eight patients with primary hypothyroidism, and five patients with hypothalamic and pituitary disorders. Blood was collected at regular intervals for the measurements of TSH, α and β-TSH subunits, T3 and PRL. Healthy euthyroid subjects exhibited biphasic increases in intact TSH as well as in α- and β-TSH subunits. Circulating TSH levels rose rapidly within 10 min of infusion to a peak in 45 min. Levels were then stable or decreasing until 90 min, when a second phase of increase occurred which was maximal at160 min. Greater responses were observed in females than in males. Primary hypothyroid patients exhibited similar biphasic increases in TSH and itssubunits as did euthyroid subjects. Patients with hypothalamic and pituitary disorders had delayed and diminished responses, while thyrotoxic patientsdid not respond at all. In euthyroid subjects, significant increases in serum T3 levels as a result of thyroidal stimulation by TSH occurred within 60−120 min and continued steadily until the end of infusion when they declined. In patients with hypothalamic and pituitary disorders, T3 levelsbegan to rise at 180 min and continued for 2 h after stopping the infusion. The PRL response in normal subjects showed a rapid increase to maximum levels within 30−45 min, followed by a gradual decrease despite continued TRH stimulation. This pattern was maintained in women on estrogen who had higher basal PRL levels. The biphasic response pattern of TSH and its subunits to TRH reflects the probable existence of two pools of TSH in the pituitary. The first is a readily releasable pool of presynthesized hormone, and the second, which required longer stimulation before release, represented newly synthesized hormone. The pattern of PRL secretion differs from that of TSH. The biphasic response of PRL is not clearly differentiated. This may be explained by an initial release phase greater than the second biosynthetic phase.