ABSTRACT
Introduction There are seven nuclear hormone receptor (NR) families, termed NR07. NR1 is a large group containing the thyroid hormone receptors, retinoic acid receptors, peroxisome proliferator-activated receptors, vitamin D, and ecdysone receptors, as well as a number of orphan receptors. NR2 consists of the retinoid-X-receptors as well as Coup-TF, HNF4 TR2, and four orphan receptors. NR3 consists of the steroid receptors (SRs), whereas NR4 are the NGFIB orphan receptors. NR5 FTZ-F1 and NR6 GCNF1 comprise orphan receptors, whereas NR0 contains gene with sequences that resemble fragments of other receptors, but whose function is unclear. The focus of this chapter is the corticosteroid hormone receptors that belong to the NR3 family, which in terrestrial vertebrates includes the sex steroid receptors-estrogen (ER), androgen (AR) and progesterone (PR), and the adrenal gland hormone receptors-the corticosteroid receptors (CRs), which are further divided into the glucocorticoid
Introduction .................................................................................................... 257 Chordate phylogeny and steroid receptors ................................................ 258 Hormone synthesis pathways ...................................................................... 260
Pituitary gland and associated peptides ................................................ 260 Steroid synthesis ........................................................................................ 262
Steroid receptors ............................................................................................. 265 Steroid receptor structure and function ................................................. 265 Steroid receptor evolution ........................................................................ 266
Functional role of corticosteroids in hagsh .............................................. 268 Conclusion ...................................................................................................... 270 Acknowledgments ......................................................................................... 271 References ....................................................................................................... 271
(GR) and mineralocorticoid (MR) receptors, as well as a group known as the estrogen-related receptors (ERRs). The primary role of the steroid receptors is to act as ligand-dependent transcription factors that enable the cell to increase the expression of target genes. This is an oversimpli-cation and some SRs act via a nongenomic pathway or inuence other hormone-signaling pathways via protein-protein interactions (e.g., Glass and Rosenfeld, 2000; Borski et al., 2001; Lee et al., 2012). The SR ligands are small lipophilic compounds that readily cross the cell membrane and include hormones such as estradiol, testosterone, and cortisol. The array of ligands and receptors present in vertebrates forms a complex system that has evolved to regulate or inuence a vast number of physiological processes (e.g., reproduction, energy metabolism, the immune system, and development) and this system is critical for interpreting the brain’s response to internal and external stimuli. Chapter 9 covers a more detailed review of the sex steroid hormone synthesis pathway in hagsh. This chapter will take a comparative approach to track the evolution of the steroid-signaling pathway, including the steroid synthesis pathway, as well as the steroid receptors, but will focus primarily on the CRs.
