The hypothalamic-pituitary-thyroid (HPT) axis is regulated by a negative feedback loop, in such a way that during primary hypothyroidism the decreased TH serum levels lead to an increased release of thyrotropin (TSH) from the adenohypophysis (AH) and to a high synthesis and release of the hypothalamic peptide thyrotropin-releasing hormone (TRH) into the portal blood in order to activate the HPT axis. The gene discussed is TRH; the disease is Primary hypothyroidism.