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Chapter 22 PART IV: Molecular Pathology of Human Disease Molecular Basis of Diseases of the Endocrine System Companion site for Molecular Pathology Author: William B. Coleman and Gregory J. Tsongalis FIGURE 22.1 The hypothalamus-pituitary-thyroid axis. Hypothalamic thyrotropin-releasing hormone (TRH) stimulates pituitary thyroid-stimulating hormone (TSH) secretion. TSH binds to TSH receptors (TSHR) in the thyroid gland (target organ) to trigger thyroid hormone (T3 and T4) secretion. Thyroid hormones are released into bloodstream and elicit their physiological functions in peripheral cells through receptor-mediated mechanism. Meanwhile, thyroid hormones inhibit further hypothalamic TRH and pituitary TSH secretion through negative feedback. A steady circulating level of thyroid hormones is thus achieved. The example shown reflects the principal mode of regulation of the hypothalamus-pituitary-target organ axis. ⇓ indicates stimulation, ⊢ indicates inhibition. NIS: sodium iodide symporter; TPO: thyroid peroxidase; TG: thyroglobulin; MIT: mono-iodotyrosyl; DIT: di-iodotyrosyl. Companion site for Molecular Pathology Copyright © 2009 by Academic Press. All rights reserved. 2 FIGURE 22.2 Pathways of adrenal steroidogenesis. The three classes of adrenal steroids are shown in bold. Enzymes or proteins that cause CAH when defective are shown in gray boxes. The 17α-hydroxylase and 17,20-lyase activities are encoded by the same enzyme (CYP17A1). Companion site for Molecular Pathology Copyright © 2009 by Academic Press. All rights reserved. 3