The Forgotten Link: Hormones, Heritage, and the Immune System

The least researched connection in the health system today may also be one of the most far-reaching: the relationship between hormones and the immune system. For decades, the immune system was viewed largely in isolation—a closed-loop network that responded to invaders and infections. But today, it’s becoming clear that the body doesn’t work in isolated silos. It operates through complex, interwoven systems, and at the heart of this integration is the role of hormones.

Hormones were first discovered in 1902 by British physiologists William Bayliss and Ernest Starling, who identified chemical messengers that traveled through the bloodstream to signal other parts of the body. They coined the term "hormone" from the Greek word hormōn, meaning “to set in motion.” That term has proven more accurate than ever, as we now understand that hormones help orchestrate everything from metabolism and growth to emotion and immunity.

The hypothalamus and pituitary gland, two key players in the endocrine system, produce hormones that regulate the growth and function of immune cells such as T-cells and plasma cells. And recent research shows that immune cells have hormone receptors, meaning they can directly respond to hormonal signals. This crosstalk suggests a tightly coordinated system where the brain, hormone glands, and immune network work together to protect the body.

But hormone influence doesn’t end with the immune system—it extends to the muscular system and aging itself. Hormones like testosterone, estrogen, growth hormone (GH), and insulin-like growth factor (IGF-1) are crucial for maintaining muscle strength and metabolism. As we age, levels of these anabolic (muscle-building) hormones tend to decline, contributing to sarcopenia, the progressive loss of muscle mass and function. At the same time, catabolic hormones like cortisol can increase, accelerating muscle breakdown.

Even deeper, changes in DNA methylation—a form of epigenetic regulation—can alter how hormone-related genes express themselves in muscle tissue. These changes affect how sensitive muscle cells are to anabolic signals, potentially blunting the body’s ability to maintain or rebuild muscle, especially in older adults. The result is a cascade of functional decline: weaker muscles, slower metabolism, reduced mobility, and a higher risk of chronic illness.

Modern science also sheds revealing light on troubling patterns from the past—patterns that, for me, became deeply personal. Around the age of thirteen, I discovered a heavy wooden chest hidden behind a locked door in my grandparents’ attic. Inside were ornate silver candleholders and delicate porcelain dishes, each engraved with a family crest I didn’t recognize. That unexpected discovery sparked years of genealogical research, ultimately leading to a startling realization: my family lineage traces back to a royal bloodline dating as far back as 1540.

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As I delved into our maternal ancestry, I began comparing old portraits and historical records—particularly those related to the Habsburg dynasty, a European royal family notorious for its long history of inbreeding. This practice, intended to preserve political alliances and territorial control, had significant biological consequences. In early portraits of young royals—such as Maria Anna, who was just four years old in one depiction and later married her first cousin, Balthasar Charles, the son of her mother’s brother—she appears with healthy, symmetrical features.
However, in later paintings, physical transformations become unmistakable: enlarged jaws, thickened facial structures, elongated chins, and pronounced jawlines—traits consistent with acromegaly, a disorder caused by excessive growth hormone secretion.

Charles II, Maria Anna’s only surviving son, was in poor health. It is believed that he initially suffered from a hormonal deficiency, followed by an excess of growth hormone (GH). As evident in contemporary portraits, his pronounced Habsburg jaw is a characteristic feature of acromegaly.

Similar traits began to emerge in the archival photographs of my own ancestors from the early 1900s. Both men and women exhibited features consistent not only with acromegaly but also with Cushing’s syndrome—a condition linked to prolonged exposure to high cortisol levels, leading to rounded faces, weight gain around the torso, and muscle weakness. What I once thought were simply strong family traits were, in hindsight, potential signs of underlying hormonal disorders passed down through generations.

Today, we recognize these changes as symptoms of hormonal disorders, likely exacerbated by genetic bottlenecks. Inbreeding can increase the risk of passing on recessive genetic mutations, some of which may impair hormone production or receptor function. These dysfunctions can ripple through generations, affecting not only appearance but immunity, metabolism, and muscle integrity.

It led me to a powerful question: How much hormonal imbalance exists today due to unknown inbreeding in our distant past? Most people don’t know their ancestral history, or how much genetic overlap may exist in their family tree. But even if we forget the past, our bodies remember. Hormonal imbalances—once hidden in family portraits—may now be silently contributing to modern health challenges like immune dysfunction, metabolic disorders, and age-related muscle loss.

In my own case, a persistent hormone imbalance was later identified, along with immune deficiencies that extended into my generation. What I once believed were isolated health issues turned out to be symptoms of a much older narrative—one written in bloodlines and biochemistry.

If we have doubts about how far our ancestral lines and genetic heritage may have spread, we need only look to events like the Thirty Years’ War—a pan-European conflict that lasted from 1618 to 1648. Though it was fought primarily within the Holy Roman Empire (in what is now modern-day Germany), it involved major powers from across the continent, including Spain, France, Sweden, Denmark, and the Dutch Republic, even reaching as far as the Americas. The scale and devastation of the war not only shifted political and religious boundaries but also caused mass migrations, intermarriages, and displacements that reshaped the demographic map of Europe. In the chaos of prolonged warfare, civilian populations mingled, soldiers settled far from their homelands, and borders were redrawn—allowing bloodlines to cross unexpectedly and extensively.

The war not only devastated populations and redrew territorial boundaries but also facilitated the movement and intermingling of soldiers, nobles, and civilians across regions. Armies were often composed of mercenaries from various nations, and the constant shifting of frontlines meant that people from vastly different cultural and ethnic backgrounds came into contact—sometimes through cooperation, often through conflict. In its aftermath, the Thirty Years’ War dramatically reshaped Europe’s political and religious landscape, weakening the Habsburgs and the Catholic Church while marking the rise of France as a dominant power. Entire towns were depopulated, agricultural lands abandoned, and regions economically ruined, resulting in widespread displacement and resettlement.

There was also a significant shortage of males in the population, a demographic imbalance that influenced marriage patterns for generations. Communities, desperate to recover, often saw increased rates of consanguineous (related) marriages, and the social disruption led to the breaking down of traditional barriers that had previously kept populations more isolated. With so much cross-border movement, forced migration, and population upheaval, the genetic legacy of that period may be far more widespread than we realize. The biological consequences of the war—whether through intermarriage, assimilation of foreign soldiers, or the survival of only certain familial lines—left traces in the DNA of modern Europeans, many of whom may unknowingly carry genetic fragments born out of one of history’s most destructive conflicts.

The link between hormones and health is no longer just theory. It is the key to understanding how systems like immunity, metabolism, and muscle aging interconnect. Hormones influence how we grow, how we fight disease, how we age, and even how we survive. And their story, once ignored or misunderstood, is only just beginning to be fully told.

As medicine moves forward with precision tools like genetic mapping and epigenetic analysis, it must also look backward—to the inherited stories etched in our cells, shaped by decisions made centuries ago. Because the future of health doesn’t just depend on new discoveries.

It depends on remembering what we once overlooked.

Endocrine regulation of the immune system
https://link.springer.com/article/10.1007/BF01721574

 

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742