Thursday, May 19, 2022

Using ancient fish, scientists reel in new insights about human biology

A fish story with a human tell.

The elephant shark (Callorhinchus milii) is an ancient fish known for its unusual looking. It has a distinctive hoe-shaped, proboscis-like snout. Also known as ghost sharks, elephant fish, and silver trumpeter, the species of the fish is generally found in waters off southern Australia.

The fish belong to the oldest group of jawed vertebrates. They have the slowest evolving genome of all known vertebrates. This makes them ideal for specific research, including how some biological systems have evolved in bony vertebrates, including humans.

In a new study, scientists at the University of California San Diego School of Medicine and in Japan used this ancient fish to get new insights into human biology. Particularly they studied how and why a widely used medication works to abort pregnancies. They compared progesterone receptor (PR) activation in elephant sharks and humans to determine how steroid activation evolved in the latter and why it works the way it does today.

They found that PR activation in elephant sharks needs a different mix of hormones and steroids than PR activation in humans, with the latter requiring fewer but more specific hormonal and steroidal triggers.

RU486 is a medically approved clinical compound that blocks or terminates a pregnancy in humans. However, scientists found that the compound does not have the same effect on elephant sharks. It did not inhibit progesterone activation of the elephant shark progesterone receptor.

Senior author Michael Baker, Ph.D., research professor at UC San Diego School of Medicine, said“The findings illuminate the divergent evolutionary paths of fish and humans, and offer insight about how other more popular animal models, specifical zebrafish, might be problematic when attempting to parse the pathology of endocrine disruption (when natural or manmade chemicals mimic or interfere with hormones that regulate development, reproduction, and other basic functions) or develop new drugs.”

Journal Reference:

  1. Xiaozhi Lin, Wataru Takagi et al. Regulation by Progestins, Corticosteroids, and RU486 of Transcriptional Activation of Elephant Shark and Human Progesterone Receptors: An Evolutionary Perspective. DOI: 10.1021/acsptsci.1c00191

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