A fish story with a man

Elephant sharks offer a new perspective on how humans evolved; a new study analyzes some previously unexplained reproductive differences.

Researchers from the University of California Medical School in San Diego and Japan have used ancient fish to gain new insights into human biology and in particular how and why widely used drugs act to terminate pregnancies (in humans, not in fish ).

The results published in the online edition of February 11, 2022 ACS Pharmacology and Translation Science.

Elephant Shark (Callorhinchus milii) is an unusual and unusual model of an animal. Known under several names such as ghost shark, elephant fish and silver trumpet, this species is found in the waters of South Australia. Smooth skin, cartilaginous fish grow to a maximum size of four feet and pose no threat to humans. Their distinctive hoe-like hoe, snout is used to detect prey, primarily mollusks and invertebrates that live on the bottom, through movement and weak electric fields.

But this other attribute makes elephant sharks suitable for certain types of research: they belong to the oldest group of jaw vertebrates and have the slowest-growing genome of all known vertebrates, making them ideal for studying how some biological systems evolved into bony vertebrates, including humans. A recent study comparing progesterone receptor (PR) activation in elephant sharks and humans provides an insight into how steroid activation evolved in the latter and why it works as it does today.

Progesterone is a hormone that in women regulates the menstrual cycle, preparation for conception and pregnancy. The effects of progesterone are mediated by its nuclear receptor, PR. Researchers have found that activating PR in elephant sharks requires a different combination of hormones and steroids than activating PR in humans, the latter requiring fewer but more specific hormonal and steroid triggers.

More interestingly, they found that RU486, a medical-approved clinical compound that blocks or terminates pregnancies in humans and is commonly referred to as the “abortion pill,” does not have the same effect on elephants. It does not interfere with the activation of progesterone PR by elephant shark.

The findings, said senior author Michael Baker, Ph.D., a research professor at UC San Diego School of Medicine, illuminate the different pathways of fish and human evolution and suggest how other more popular animal models, particularly zebrafish, can be problematic when tried. analyze the pathology of endocrine disorders (when natural or artificial chemicals mimic or interfere with hormones that regulate development, reproduction and other basic functions) or develop new drugs.

Reference: “Regulation of transcriptional activation of elephant shark and human progesterone receptors by progestins, corticosteroids and RU486: an evolutionary perspective” Xiaoji Lina, Vataru Takagi, Susumu Hyoda, Shigeho Idiri, Yoshinao Ba Katsu and December 6 E20. , ACS Pharmacology and Translation Science.
DOI: 10.1021 / acsptsci.1c00191

Co-authors: Xiaoji Lin, Shigeho Idiri and Yoshinao Katsu, Hokkaido University, Japan; and Wataru Takagi and Susumu Hyoda, University of Tokyo