Evolution of adrenal and sex steroid action in vertebrates: a ligand‐based mechanism for complexity

Abstract

SummaryVarious explanations have been proposed to account for complex differentiation and development in humans, despite the human genome containing only two to three times the number of genes in invertebrates. Ignored are the actions of adrenal and sex steroids-androgens, estrogens, glucocorticoids, mineralocorticoids, and progestins-which act through receptors that arose from an ancestral nuclear receptor in a protochordate. This ligand-based mechanism is unique to vertebrates and was integrated into the already robust network of transcription factors in invertebrates. Adrenal and sex steroids influence almost all aspects of vertebrate differentiation and development. I propose that evolution of this ligand-based mechanism in a primitive vertebrate was an important contribution to vertebrate complexity. Sequencing of genomes from a cephalochordate, such as amphioxus, and from hagfish and lamprey will establish early events in the evolution of steroid hormone signaling, and also allow genetic studies to elucidate how vertebrate complexity depends on steroid hormones.

Co-evolution of steroidogenic and steroid-inactivating enzymes and adrenal and sex steroid receptors

“…Thus far, adrenal and sex steroid receptors have been found only in vertebrates (Baker, 2002a(Baker, , 2003. This is consistent with PCR analysis of DNA from phylogenetically diverse animals (Escriva et al 1997) and sequence analysis steroid receptors (Baker, 1997(Baker, , 2001b(Baker, , 2003Escriva et al, 2000), both of which conclude that adrenal and sex steroid receptors arose at the beginning of the vertebrate line.…”

“…As will be discussed in this article, steroid receptors, steroidogenic enzymes and steroid-inactivating enzymes arose at about the same time in primitive vertebrates, and the subsequent co-evolution of these proteins was important in the evolution of complex developmental pathways found in vertebrates (Baker, 2003). Moreover, understanding the early events in the evolution of steroidogenic enzymes may shed light on adrenarche (Arlt et al 2002;Rainey et al, 2002) and the actions of neurosteroids (Baulieu and Robel, 1998;Compagnone and Mellon, 1998) in humans.…”

“…An analysis of the recently completed genome of Ciona indicates that this organism does not have receptors for adrenal and sex steroids (Dehal et al 2002;Baker, 2003). Together these analyses suggest that adrenal and sex steroid receptors arose in a cephalochordate, such as amphioxus, or in a jawless fish [ Figure 1].…”

“…Bony fish contain adrenal and sex steroid receptors and steroidogenic and steroid-inactivating enzymes. BLAST searches of the genome of Ciona intestinalis with these mammalian and fish sequences reveals that Ciona lacks genes coding for adrenal and sex steroid receptors and many of the key enzymes necessary for steroid synthesis (Dehal et al 2002;Baker 2003). This suggests that the ancestral steroid receptor arose in a cephalochordate such as amphioxus (Baker, 1997(Baker, , 2001b.…”

Trichoplax, the simplest known animal, contains an estrogen-related receptor but no estrogen receptor: Implications for estrogen receptor evolution

“…The absence of an invertebrate ER outside of lophotrochozoans and the absence of an invertebrate ER in the recently completed sea urchin genome [34] indicate that a steroid-binding ER evolved in deuterostome [25,26], which would mean that vertebrate and invertebrate ERs have two distinct ancestors.…”