Chapter 24: Gonadal Steroids Katrien Venken, Steven Boonen, Roger Bouillon, and Dirk Vanderschueren

Figure 1 Figure 1 Overview of the metabolism and action of sex steroids in men. HSD, hydroxysteroid dehydrogenase. © 2008 American Society for Bone and Mineral Research From the Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 7 th Edition.

Figure 2 Figure 2 Diagrammatic representation of the domain structure of nuclear receptors. The A/B domain at the NH2 terminus contains the AF-1 site where other transcription factors interact. The C/D domain contains the two-zinc finger structure that binds to DNA, and the E/F domain contains the ligand binding pocket and the AF-2 domain that directly contacts co-activator peptides. © 2008 American Society for Bone and Mineral Research From the Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 7 th Edition.

Figure 3 Figure 3 Genomic and nongenomic gonadal steroid signaling. Genomic action: the ligand binds to its specific receptor, which induces a conformational change. The receptor translocates to the nucleus and undergoes dimerization. The receptor dimer binds to specific DNA sequences, so-called hormone response elements. The DNA bound receptor contacts the general transcription initiation complex (TIC) either directly or indirectly through co-regulatory proteins (CoR). Nongenomic action: the ligand binds a, yet undefined, plasma membrane receptor, which results in the activation of second messenger signal transduction pathways including Ca2+, (PLC), cAMP, phospholipase C, diacylglycerol (DAG), protein kinase C (PKC). ER, estrogen receptor; AR, androgen receptor; PR, progesterone receptor; HRE, hormone response element. © 2008 American Society for Bone and Mineral Research From the Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 7 th Edition.

Figure 4 Figure 4 Schematic representation of the antiresorptive action of estrogen on bone. Estrogen downregulates the production in bone of cytokines involved in bone resorption, such as IL-1, TNF-α, IL-6, GM-CSF, and M-CSF. Downregulation of these cytokines decreases the number and activity of osteoclasts. Estrogen also decreases TGF-β, resulting in a decreased osteoclast number and activity and increased osteoclast apoptosis. Estrogen increases OPG, the decoy receptor of RANKL in binding to its receptor RANK on osteoclasts. © 2008 American Society for Bone and Mineral Research From the Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 7 th Edition.