Thyrotropin-releasing hormone time-dependently influences thyrotropin microheterogeneity - an in vivo study in euthyroidism

Thyrotropin (TSH) is secreted not as one distinct hormone, but rather as a group of isohormones which differ in their oligosaccharide composition. Alt hough the mechanisms regulating TSH glycosylation are not fully understood, there is strong evidence that TRH plays an important role. The aim of our study was to determine the dynamic influence of TRH on TSH microheterogenei ty. Sera were obtained from euthyroid volunteers (n=20) before and 30, 60, 120, 180 and 240 min after intravenous, nasal and oral administration of TRH in three independent runs (randomized order, at a time-interval of 3 weeks be tween each run). TSH was immune-concentrated and analysed by isoelectric fo cusing (IEF) and lentil lectin affinity chromatography. TSH immunoreactivit y was measured by an automated second-generation TSH immunoassay. Overall, serum TSH concentrations reached maximal values 30 min after intravenous, 6 0 min after nasal and 180 min after oral TRH stimulation. IEF analysis reve aled 63.3 +/- 3.3% of pituitary standard TSH (IRP 80/558) in the neutral pH range (8>pH>6). In contrast, 30 min after TRH stimulation 80.8+/-3.7% (P<0 .001) and 60 min after TRH stimulation 44.9 +/- 2.2% (P<0.001) of the TSH o f euthyroid probands were found in this pH range, whereas 180 min after TRH stimulation 58.4 +/- 2.3% (P<0.001) were detected in the acidic pH range ( pH<6). This shift of TSH composition in euthyroidism after TRH stimulation was confirmed by lentil lectin analysis of TSH: core-fucose content of euth yroid TSH was 73.4 +/- 3.8% 30 min and 22.9 +/- 3.2% 120 min after TRH stim ulation in contrast to basal (53.3 +/- 1.8%; P<0.001) and pituitary standar d (IRP 80/558) TSH (63.0+/- 09%; P<0.001). In conclusion, in euthyroidism, TRH stimulation time-dependently changes th e distribution pattern of the TSH isoforms from an alkaline and neutral to a more acidic one. This corresponds to the secretion of isohormones with al tered bioactivity which could influence the fine-tuning of thyroid function .