Suppression of Cold-Stimulated Thyrotropin Secretion by Antiserum to Thyrotropin-Releasing Hormon

The role of TRH in the cold-mediated activation of the hypothalamo-pituitary-thyroid axis was assessed in rats by passive immunization with anti-TRH serum (TRH-AS). The TRH-AS was capable of detecting 3 pg of TRH by radioimmunoassay, had an affinity constant (Ka) of 9.7 × 108 liters/mole, an antibody-binding capacity (AB) of 3.8 × 10−6 moles/liter and showed no significant cross-reactivity with other hypothalamic peptides or angiotensin. Intravenous administration of 0.5 ml TRH-AS into conscious rats with indwelling right atrial catheters led to a significant suppression of the cold-induced TSH rise at 30 and 60 min. A similar suppression of cold-induced TSH release at 30 and 60 min was observed in rats with right atrial catheters adapted to a 30 C environment for one week prior to cold exposure. The TSH response to exogenous TRH administration was not inhibited by prior injection of TRH-AS or by preincubation of the peptide with the IgG fraction of the antiserum. The failure to neutralize the effect of exogenous TRH is in contrast to our ability to neutralize that of endogenous TRH and is attributed to the much larger quantity of exogenous peptide needed to elicit a response. Antiserum titers of passively immunized rats were significantly higher following iv than following ip administration. The results provide evidence for the role of TRH in mediating the cold-induced stimulation of TSH secretion.