Endocrine Abstracts

3-iodothyronamine (T₁AM) is a novel, endogenous rapid acting biogenic amine, which is a potent agonist of the G-protein coupled trace amine-associated receptor 1, TAAR1. It has been suggested that endogenous T₁AM could be generated by enzymatic deiodonation and decarboxylation of T4. The presence of T₁AM in rat brain and the distribution of the TAAR1 receptor in the hypothalamus suggest that T₁AM may affect food intake and regulate endocrine function.

We examined the effect of intraperitoneal (i.p.) administration of T₁AM on food intake, oxygen consumption and locomotor activity in mice. Peripheral administration of T₁AM to satiated mice led to a significant increase in food intake 1 hr post-injection [0.07±0.006 g (vehicle) vs. 0.1±0.009 g (4.0 nmol/kg)]. Oxygen consumption (VO₂) and respiratory exchange ratio (RER) analysis demonstrated this increase in feeding was independent of energy expenditure.

To examine its CNS effects, T₁AM was administered intracerebroventricularly to male rats and food intake and plasma hormones determined. Intracerebroventricular (ICV) administration of T₁AM to rats significantly increased food intake 1 hr post-injection [1.48±0.39 (vehicle) vs. 3.08±0.82 g (1.2 nmol/kg)]. T₁AM had no effect on levels of plasma thyroid hormones, corticosterone, glucagon, insulin and glucose. TAAR1 mRNA expression was determined in rat brains using an antisense riboprobe. Expression of TAAR1 mRNA was found in the paraventicular nucleus (PVN), ventromedial nucleus, and arcuate nucleus (ARC). Expression of c-fos was increased in the ARC following lateral ventricle administration of T₁AM (1.2 nmol/kg) in male rats. Direct administration of T₁AM (0.12 nmol/kg) into the ARC of satiated rats resulted in a significant increased in food intake [0.44±0.10 g (vehicle) vs. 1.6±0.31 g (0.12 nmol/kg)] 1 hr post-injection. To investigate a possible mechanism of action, the effects of T₁AM on the release of orexigenic neuropeptides from ex-vivo hypothalamic explants was determined. T₁AM resulted in an increase in NPY release.

These data demonstrate a novel orexigenic role for T₁AM, which may suggest a possible non-genomic mechanism for the action of thyroid hormone. This effect proposed to be mediated via the ARC.