Unlocking the Secrets of Female Physiology

Unlocking the Secrets of Female Physiology

Holly Ingraham, PhD, is unlocking the secrets of female physiology. Explore her work on hormone impacts, brain-bone connections and women's health. 

Holly Ingraham, PhD, was just a child the first time she peered down the eyepiece of a microscope and let her mind fill with wonder.

She had collected some water samples at a swampy pond in California’s Bay Area suburb of Walnut Creek, then an uncrowded locale populated with pear orchards. When she slid the samples under the lens of an 1890 Bausch and Lomb microscope—a family heirloom from her great-grandfather—she was amazed to discover that all sorts of tiny things were moving around in a single droplet of water.

“I thought, ‘This is really cool,’” Ingraham says. “I got intrigued.”

She took that early passion for science through her years in high school, where she was fascinated by the structure of DNA, and thrived in chemistry class, each experiment serving as a fun puzzle for Ingraham to solve.

In the decades since, Ingraham hasn’t strayed very far from those interests. Today she is a professor of cellular molecular pharmacology at the University of California, San Francisco, where her research focuses on unlocking the secrets of female physiology. 

“Most of what we think about in terms of female physiology is all centered around just reproductive issues … and in health, it all has been focused primarily on breast cancer,” Ingraham says. “But we are missing many more dimensions in women’s health, resulting from the dynamic and adaptive responses in female physiology across the lifespan.”

Through her research, Ingraham is trying to broaden the focus and understand how hormone fluctuations throughout a female’s life impact physiological systems, such as neuronal circuits in the brain.

She’s especially proud of a July 2024 Nature article she co-authored, A Maternal Brain Hormone that Builds Bone. It outlines a newly discovered hormone that plays a role in strengthening bones for women who are losing calcium to produce breast milk.

She described the discovery as “one of those unusual moments in one’s career,” where things come together and “the science is beautiful and exquisite.” But she got there almost by accident. 

Ingraham and her lab started out trying to understand what estrogen signaling was doing in one region of the brain. They planned to use an EchoMRI machine to conduct experiments, but on this particular day the machine was broken, forcing them to pivot to use a DXA machine instead, which yields detailed information about bone density.

The bone density results were surprising to Ingraham, motivating her group to investigate why a sex-specific increase in bone density was observed. Following up on this tangent led to the discoveries published in the Nature article and has opened up a new research interest in her lab.

Ingraham, who is the recipient of the 2024 Federation of American Societies for Experimental Biology Excellence in Science Lifetime Achievement Award, will be sharing more about her work during a keynote address at the 2025 American Physiology Summit. She plans to walk through her brain-bone study and also talk about emerging research on how estrogen may increase gut sensitivity in females.

What excites her most is the way her current work is forcing her to look at multiple body systems at once—from the brain to the gut and the bones. This broader approach counters the tendency some physiologists have to focus only on their “favorite organ,” she says.

“After all, physiology is the integration and control of multiple systems and there is much more to be discovered,” she says.

This article was originally published in the January 2025 issue of The Physiologist Magazine. Copyright © 2025 by the American Physiological Society. Send questions or comments to tphysmag@physiology.org.