Aetiology of thyroidal dysfunction in murine toxoplasmosis

Abstract

Mice infected with Toxoplasma gondii manifest a rapid decline in serum thyroxine (T₄) levels. To locate the locus of the hypothyroxinaemia, the integrity of the pituitary–thyroid axis of infected mice was assessed by a thyrotropin-releasing hormone (TRH) assay. A rise in serum T₄ after inoculation of TRH implies the release of thyrotropin (thyroid-stimulating hormone) from a functionally intact pituitary. Administration of a single, large-dose (1 μg) bolus of TRH to infected mice induced a positive, although subnormal, T₄ response. In contrast, when infected mice were pre-treated with a series of low-dose (5 ng) pulses of TRH prior to the bolus challenge, the T₄ response was markedly enhanced. We suggest that the multiple inoculations of low-dose pulses of TRH ‘primed’ the pituitary (and secondarily the thyroid) and led to replenishment of their readily available hormone reserves and the heightened response to stimulation. These observations indicate that the locus of thyroid dysfunction is in the hypothalamus, not the pituitary or thyroid, and apparently involves impairment of the pulsatile release of TRH.