Divergent Evolution of Progesterone and Mineralocorticoid Receptors in Terrestrial Vertebrates and Fish Influences Endocrine Disruption

10.20944/preprints202111.0396.v1 ◽

2021 ◽

Author(s):

Michael Baker

Keyword(s):

Binding Sites ◽

Endocrine Disrupting Chemicals ◽

Divergent Evolution ◽

Industrial Chemicals ◽

Elephant Shark ◽

Terrestrial Vertebrates ◽

Terrestrial Vertebrate ◽

Endocrine Disrupting ◽

Development And Differentiation ◽

Potent Agonist

There is much concern about disruption of endocrine physiology regulated by steroid hormones in humans, other terrestrial vertebrates and fish by industrial chemicals, such as bisphenol A, and pesticides, such as DDT. These endocrine-disrupting chemicals influence steroid-mediated physiology in humans and other vertebrates by competing with steroids for receptor binding sites, disrupting diverse responses involved in reproduction, development and differentiation. Here I discuss that due to evolution of the progesterone receptor (PR) and mineralocorticoid receptor (MR) after ray-finned fish and terrestrial vertebrates diverged from a common ancestor, each receptor evolved to respond to different steroids in ray-finned fish and terrestrial vertebrates. In elephant shark, a cartilaginous fish, ancestral to ray-finned fish and terrestrial vertebrates, both progesterone and 17,20-beta-dihydroxy-progesterone activate the PR. During the evolution of ray-finned fish and terrestrial vertebrates, the PR in terrestrial vertebrates continued responding to progesterone and evolved to weakly respond to 17,20-beta-dihydroxy-progesterone. In contrast, the physiological progestin for the PR in zebrafish and other ray-finned fish is 17,20-beta-dihydroxy-progesterone, and ray-finned fish PR responds weakly to progesterone. The MR in fish and terrestrial vertebrates also diverged to have different responses to progesterone. Progesterone is a potent agonist for elephant shark MR, zebrafish MR and other fish MRs, in contrast to progesterone’s opposite activity as an antagonist for aldosterone, the physiological mineralocorticoid for human MR. These different physiological ligands for fish and terrestrial vertebrate PR and MR need to be considered in applying data for their disruption by chemicals in fish and terrestrial vertebrates to each other.

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Novel Pathways of Endocrine Disruption Through Pesticides Interference With Human Mineralocorticoid Receptors

Toxicological Sciences ◽

10.1093/toxsci/kfx244 ◽

2017 ◽

Vol 162 (1) ◽

pp. 53-63 ◽

Cited By ~ 14

Author(s):

Jianyun Zhang ◽

Xin Huang ◽

Hongling Liu ◽

Weiping Liu ◽

Jing Liu

Keyword(s):

Endocrine Disruption ◽

Mineralocorticoid Receptors

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Steroid Receptors and Vertebrate Evolution

10.32942/osf.io/kpdfq ◽

2019 ◽

Author(s):

Michael Baker

Keyword(s):

Estrogen Receptor ◽

Stress Responses ◽

Steroid Receptors ◽

Estrogen Receptor Α ◽

Cambrian Explosion ◽

Mineralocorticoid Receptors ◽

Basal Chordates ◽

Terrestrial Vertebrates ◽

Evolutionary Success ◽

Life On Earth

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 an estrogen receptor and a 3-ketosteroid receptor first appearing in basal chordates (cephalochordates: amphioxus), which are close ancestors of vertebrates. Through gene duplication and divergence of the 3-ketosteroid receptor, receptors that respond to androgens, glucocorticoids, mineralocorticoids and progestins evolved in vertebrates. Thus, 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, distinct glucocorticoid and mineralocorticoid receptors and estrogen receptor-α and -β in cartilaginous fishes (gnathostomes: sharks). Further evolution of mineralocorticoid signaling occurred with the evolution of aldosterone synthase in lungfish, a forerunner of terrestrial vertebrates. Adrenal and sex steroid receptors are not found in echinoderms: and hemichordates, which are ancestors in the lineage of cephalochordates and vertebrates. The evolution of steroid receptors at key nodes in the evolution of vertebrates, in which 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).

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