Steroid Receptors and Vertebrate Evolution

Abstract

Considering that life on earth evolved about 3.7 billion years ago, vertebrates are young, appearing in the fossil record during the Cambrian explosion about 542 to 515 million years ago.  Results from sequence analyses of genomes from bacteria, yeast, plants, invertebrates and vertebrates indicate that receptors for adrenal steroids (aldosterone, cortisol), and sex steroids (estrogen, progesterone, testosterone) also are young, with receptors for estrogens and 3-ketosteroids first appearing in basal chordates (cephalochordates: amphioxus), which are close ancestors of vertebrates.  An ancestral progesterone receptor and an ancestral corticoid receptor, the common ancestor of the glucocorticoid and mineralocorticoid receptors, evolved in jawless vertebrates (cyclostomes: lampreys, hagfish).  This was followed by evolution of an androgen receptor and distinct glucocorticoid and mineralocorticoid receptors in cartilaginous fishes (gnathostomes: sharks).  Adrenal and sex steroid receptors are not found in echinoderms: and hemichordates, which are ancestors in the lineage of cephalochordates and vertebrates.  The presence of steroid receptors in vertebrates, in which these steroid receptors act as master switches to regulate differentiation, development, reproduction, immune responses, electrolyte homeostasis and stress responses, argues for an important role for steroid receptors in the evolutionary success of vertebrates, considering that the human genome contains about 22,000 genes, which is not much larger than genomes of invertebrates, such as Caenorhabditis elegans (~18,000 genes) and Drosophila (~14,000 genes).

Cortisol promotes stress tolerance via DAF-16 in Caenorhabditis elegans

“…C. elegans worms share hormones such as estrogen and oxytocin with humans but do not possess cortisol [ 12 , 13 , 16 , 24 ]. However, pregnenolone, a precursor of many steroid hormones, is present in C. elegans and has been found to prolong C. elegans lifespan [ 15 ].…”

“…Although C. elegans possesses some steroid hormone signaling molecules, such as estrogen and dafachronic acid, the full spectrum of cortisol effects in C. elegans is unclear [ [13] , [14] , [15] ]. Furthermore, a previous molecular evolution study suggested that invertebrates do not have GRs [ 16 ]. Nevertheless, C. elegans has been reported to possess DHS-30, an ortholog of human dehydrogenase/reductase SDR family member 7B (DHRS7B), which affects steroid hormone synthesis, and the ACTH-releasing hormone receptor SEB-3 [ 17 , 18 ].…”

Roles of Estrogens in the Healthy and Diseased Oviparous Vertebrate Liver

“…Estrogen receptor subtypes emerged in cartilaginous fishes (Chondrichthyes like sharks), which have skeletons composed of cartilage rather than bone. This duplication of the receptors promoted the diversification of signaling by estrogens that readily diffuse through cell membranes [ 65 , 66 , 67 ]. As mentioned above for zebrafish, the teleost lineage has at least three estrogen receptors, esr1 (α subtype), esr2b , and esr2a (β subtypes), which are the results of a whole genome duplication that occurred in the evolution of this lineage [ 68 , 69 , 70 ].…”