New clues from fruit flies about the critical role of sex hormones in
stem cell control

Date:
July 9, 2020
Source:
Huntsman Cancer Institute
Summary:
In one of the first studies addressing the role of sex hormones'
impact on stem cells in the gut, scientists outline new insights
showing how a steroidal sex hormone, ecdysone, drastically alters
the way intestinal stem cells behave, ultimately affecting the
overarching structure and function of this critical organ.



FULL STORY ==========================================================================
In one of the first studies addressing the role of sex hormones' impact
on stem cells in the gut, scientists outline new insights showing how a steroidal sex hormone, that is structurally and functionally similar
to human steroid hormones, drastically alters the way intestinal
stem cells behave, ultimately affecting the overarching structure
and function of this critical organ. The authors found that ecdysone,
a steroid hormone produced by fruit flies, stimulates intestinal stem
cell growth and causes the gut of the female fruit fly to grow in size,
and induces other critical changes. The study also provides a mechanism
to account for sex-specific roles for intestinal stem cells in normal gut function. Moreover, the research presents evidence that gut hormones may accelerate tumor development. The findings, reported jointly by Huntsman
Cancer Institute (HCI) at the University of Utah (U of U) and the German
Cancer Research Center (DKFZ), are published today in the journal Nature.


========================================================================== Bruce Edgar, PhD, a stem cell biologist at HCI and professor of
oncological sciences at the U of U, together with Aurelio Teleman, PhD, division head at DKFZ and professor at Heidelberg University jointly led
the work. They asked whether sex hormones affect intestinal stem cells'
ability to multiply and contribute to gut growth. "My lab and many others around the world have studied the Drosophila gut for some time to better understand how stem cells are regulated," says Edgar. "We knew that male
and female fruit flies exhibited differences in their intestine -- for
example, the female's intestine is larger than the male's, and females
develop intestinal tumors much more readily than males -- but we didn't
know why." This study adds significant insights into these differences,
and how they arise.

The Edgar and Teleman teams found that ecdysone, a sex-specific hormone,
can drastically alter the growth properties of stem cells in an organ
that, remarkably, is not directly involved in reproduction. They found
that these changes affect the structure and function of the entire
organ. They discovered that subjecting male flies to ecdysone caused
their otherwise slow dividing stem cells to divide as fast as in females, leading to intestinal growth in males as well. This suggests that the
limiting difference between the division of stem cells in male and female
flies is the circulating levels of the hormone.

This process confers both advantages and disadvantages to the female fruit
fly during the course of its life. Initially, more ecdysone in females
helps with the evolutionarily critical processes of reproduction. It
promotes gut enlargement, facilitating nutrient absorption, which helps
the fly lay more eggs. But later in life, the ecdysone hormone, produced
by the ovaries, eventually causes gut disfunction that can shorten the
lifespan in female fruit flies by creating an environment that favors
tumor growth. While humans don't produce ecdysone, they do have related
steroid hormones such as estrogen, progesterone and testosterone, which
have similar mechanisms of action.

The experimental work on this study was performed primarily by Sara Ahmed,
a joint PhD student between the Edgar and Teleman labs at the Zentrum fu"r Molekulare Biologie der Universita"t Heidelberg (ZMBH) and the DKFZ. Ahmed designed experiments utilizing various genetic tools to switch genes on
and off in different cell types in the fly's intestine and in its ovaries, which produce ecdysone. "Our study provides conclusive evidence that
sex hormones alter the behavior of non-sex organs like the intestine,"
says Ahmed. She further speculates that long-term implications of this
research may include exploration of new paths to treating human cancers.

According to the researchers, understanding whether a similar stem
cell-hormone relationship operates in human organs will require further studies. They plan to explore this in the future. In addition to the
critical role played by sex hormones in intestinal stem cell behavior,
the authors believe this study in Drosophila potentially unveils a new mechanism that may play out in human physiology and pathology. Insights
from this study add to a growing body of work showing that the incidence cancers of non-reproductive organs, including colon and gastric cancers,
are different in males and females.

This study was supported by the National Institutes of Health including
the National Cancer Institute P30 CA01420114, the National Institute
of General Medical Sciences R01 124434, the European Research Council AdG268515, DKFZ, and Huntsman Cancer Foundation.


========================================================================== Story Source: Materials provided by Huntsman_Cancer_Institute. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Sara Mahmoud H. Ahmed, Julieta A. Maldera, Damir Krunic, Gabriela O.

Paiva-Silva, Clothilde Pe'nalva, Aurelio A. Teleman, Bruce A. Edgar.

Fitness trade-offs incurred by ovary-to-gut steroid signalling in
Drosophila. Nature, 2020; DOI: 10.1038/s41586-020-2462-y ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200709092502.htm

--- up 24 weeks, 2 days, 2 hours, 34 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1337:3/111)