A fish story with a human tell

Date:
February 17, 2022
Source:
University of California - San Diego
Summary:
Elephant sharks offer a novel perspective on how humans evolved. A
new study parses some previously unexplained reproductive
differences.



FULL STORY ========================================================================== Researchers at University of California San Diego School of Medicine and
in Japan have used an ancient fish to reel in new insights about human
biology and, in particular, how and why a widely used medication works
to abort pregnancies (in people, not fish).


==========================================================================
The findings published in the February 11, 2022 online issue of ACS Pharmacology & Translational Science.

The elephant shark (Callorhinchus milii) is an unusual looking and
uncommon animal model. Known by several names, such as ghost shark,
elephant fish and silver trumpeter, the species is found in waters
off southern Australia. The smooth-skinned, cartilaginous fish grows
to a maximum size of four feet and poses no threat to humans. Their
distinctive hoe-shaped, proboscis-like snout is used to detect prey,
primarily shellfish and bottom-dwelling invertebrates, through movement
and weak electrical fields.

But it's a different attribute that makes elephant sharks suitable
for certain kinds of research: They belong to the oldest group of jawed vertebrates and have the slowest evolving genome of all known vertebrates, which make them ideal for investigating how some biological systems
have evolved in bony vertebrates, including humans. The latest study,
comparing progesterone receptor (PR) activation in elephant sharks and
humans, provides insights in how steroid activation evolved in the latter,
and why it works the way it does today.

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

More interestingly, they discovered that RU486, a medically approved
clinical compound that blocks or terminates pregnancy in humans and is
commonly called "the abortion pill," does not have the same effect in
elephant sharks. It does not inhibit progesterone activation of elephant
shark PR.

The findings, said senior author Michael Baker, PhD, research professor at
UC San Diego School of Medicine, illuminate the divergent evolutionary
paths of fish and humans, and offer insight about how other more
popular animal models, specifically 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.

Co-authors include: Xiaozhi Lin, Shigeho Ijiri
and Yoshinao Katsu, Hokkaido University, Japan;
and Wataru Takagi and Susumu Hyodo, University of Tokyo ========================================================================== Story Source: Materials provided by
University_of_California_-_San_Diego. Original written by Scott La
Fee. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Xiaozhi Lin, Wataru Takagi, Susumu Hyodo, Shigeho Ijiri, Yoshinao
Katsu,
Michael E. Baker. Regulation by Progestins, Corticosteroids,
and RU486 of Transcriptional Activation of Elephant Shark and
Human Progesterone Receptors: An Evolutionary Perspective. ACS
Pharmacology & Translational Science, 2021; 5 (2): 52 DOI:
10.1021/acsptsci.1c00191 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220217122355.htm

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