Origin of an Ancient Hormone/receptor Couple Revealed by Resurrection of an Ancestral Estrogen

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2017 Apr 25

PMID 28435861

Citations 17

Authors

Gabriel V Markov

Juliana Gutierrez-Mazariegos

Delphine Pitrat

Isabelle M L Billas

Francois Bonneton

Dino Moras

Jens Hasserodt

Guillaume Lecointre

Vincent Laudet

Affiliations

Soon will be listed here.

Abstract

The origin of ancient ligand/receptor couples is often analyzed via reconstruction of ancient receptors and, when ligands are products of metabolic pathways, they are not supposed to evolve. However, because metabolic pathways are inherited by descent with modification, their structure can be compared using cladistic analysis. Using this approach, we studied the evolution of steroid hormones. We show that side-chain cleavage is common to most vertebrate steroids, whereas aromatization was co-opted for estrogen synthesis from a more ancient pathway. The ancestral products of aromatic activity were aromatized steroids with a side chain, which we named "paraestrols." We synthesized paraestrol A and show that it effectively binds and activates the ancestral steroid receptor. Our study opens the way to comparative studies of biologically active small molecules.

Citing Articles

Lack of membrane sex steroid receptors for mediating rapid endocrine responses in molluscan nervous systems.

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Nuclear Receptors and the Hidden Language of the Metabolome.

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Studies on a widely-recognized snail model species () provide further evidence that vertebrate steroids do not have a hormonal role in the reproduction of mollusks.

Fodor I, Schwarz T, Kiss B, Tapodi A, Schmidt J, Cousins A Front Endocrinol (Lausanne). 2022; 13:981564.

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