The research team, led by Anja Schroff of the Department of Medical Radiation Sciences, set out to answer a deceptively simple question with major implications for both medicine and emergency preparedness. Iodine-131 is a workhorse of nuclear medicine, used for decades to treat hyperthyroidism and certain thyroid cancers, because the thyroid gland eagerly hoards iodine to build its hormones. But the same isotope is also a signature component of nuclear accident fallout. Understanding exactly how much radiation each organ receives after exposure — and whether that dose differs between males and females, or between the young and the grown — is essential both for optimizing therapy and for refining risk estimates after a nuclear emergency.

To probe the question, the researchers gave male and female Sprague–Dawley rats a controlled internal exposure of 0.36 megabecquerels of iodine-131 at one of two life stages: five weeks of age, representing a young, still-developing animal, and seventeen weeks of age, representing adulthood. Over the following six days, they measured the activity concentration of the isotope in sixteen vital tissues at six time points, ranging from one hour to 144 hours after injection. From these time-activity data, they calculated the mean absorbed dose delivered to each organ, using both analytical methods and Monte Carlo simulations to cross-check their estimates.

The results were striking. As expected, the thyroid gland dominated the picture, showing the highest iodine-131 activity concentration of any tissue in every group — peaking at 18 hours after exposure in males and 24 hours in females, regardless of whether the animals were young or adult. Every other tissue lagged far behind, with the stomach, which also expresses iodine-transporting machinery, coming in a distant second. But the real story lay in the differences between groups, which proved to be anything but subtle.

Female rats consistently accumulated more iodine-131 in their thyroids than males, and — critically — they retained it longer. That combination of higher uptake and slower clearance translated directly into higher radiation dose. The absorbed dose to the thyroid ranged across the study groups from 23 gray per megabecquerel in adult males to a staggering 100 gray per megabecquerel in young females — a more than fourfold difference driven entirely by biological sex and age at exposure. Statistically significant sex differences emerged in all sixteen tissues examined, with the most pronounced effect in the thyroid itself.

Age mattered too, though in a sex-specific way. The most notable age-related differences in thyroid uptake and absorbed dose appeared in males: young males showed markedly higher iodine-131 uptake than adult males, resulting in a substantially greater thyroid dose. In females, whose thyroid uptake was already elevated, the age effect was less prominent. This pattern suggests that the developing thyroid — or the hormonal and metabolic milieu surrounding it — handles iodine differently depending on both its maturity and the animal’s sex, compounding rather than simply adding to the sex effect.

To understand the mechanism behind these differences, the team turned to the sodium-iodide symporter, or NIS, the membrane protein responsible for actively pumping iodide into thyroid cells. Using immunohistochemistry and western blot analysis, they quantified NIS protein expression in thyroid tissue across all groups. The result was a surprise: despite the dramatic differences in uptake and dose, NIS protein levels showed high individual variability but no clear, consistent difference between the groups. Whatever drives females and young animals to accumulate and retain more radioactive iodine, it appears not to be a simple matter of having more of the iodine transporter — hinting at deeper biological factors, perhaps involving hormone regulation, thyroid size, iodine turnover kinetics, or clearance pathways that have yet to be pinned down.

The implications reach well beyond the laboratory. After Chernobyl, epidemiological studies documented a surge in thyroid cancer among people exposed as children to iodine-131 fallout, with the increase particularly pronounced among young girls — a pattern that has long suggested some combination of biological susceptibility and dosimetric difference. This study provides the first rigorous experimental evidence that the dose itself may differ systematically by sex and age, meaning that part of the observed cancer excess could reflect the fact that young females simply received more radiation to their thyroids from the same environmental exposure. The authors are careful to note that dosimetry alone cannot explain everything — biology at the cellular level certainly contributes — but the fourfold dose range they measured is far too large to ignore in risk models.

For nuclear medicine, the findings carry a more immediate practical message. Radioiodine therapy is prescribed to patients of both sexes and all ages, yet dosing protocols have historically been built on assumptions that may not hold uniformly across the population. If sex and age influence thyroid uptake and retention as strongly in humans as they do in rats, personalized dose planning — adjusting administered activity for patient sex and age — could improve therapeutic efficacy while sparing healthy tissue. The study also underscores the value of including both sexes and multiple age groups in preclinical radiopharmaceutical research, a practice that remains inconsistent across the field.

The Gothenburg team, whose work was supported by the Swedish Radiation Safety Authority, the Swedish Research Council, and the Swedish Cancer Society, among others, emphasizes that further research is needed to clarify the underlying biological and mechanistic drivers of the observed differences. Untangling whether hormonal status, thyroid growth dynamics, renal clearance, or other factors govern the sex- and age-dependent handling of iodine will be the next step. But the core conclusion stands on its own: when it comes to radioactive iodine, who you are and how old you are when exposure happens can change the dose your thyroid receives by a factor of four — a biological reality that both radiation oncologists and emergency planners can no longer afford to overlook.

Subject of Research: How sex and age at exposure influence the biodistribution and absorbed dose of radioactive iodine-131 in rats

Article Title: Sex and age at exposure influence 131I biodistribution and dosimetry in Sprague–Dawley rats

Article References: Schroff, A., Insulander Björk, K., Rassol, N., Johansson, J., Lundberg, T., Bakr, H., Andersson, M., Spetz, J., & Forssell-Aronsson, E. (2026). Sex and age at exposure influence 131I biodistribution and dosimetry in Sprague–Dawley rats. Biology of Sex Differences. https://doi.org/10.1186/s13293-026-00989-4

Image Credits: AI Generated

DOI: 10.1186/s13293-026-00989-4

Keywords: radioiodine, iodine-131, thyroid, dosimetry, biodistribution, sex differences, Chernobyl, thyroid cancer, sodium-iodide symporter, radiation protection, Sprague-Dawley rats, nuclear medicine

The research, conducted by Christopher J. Petty of the University of Georgia, Mindy Isaman and Linnea R. Freeman of Furman University, and colleagues at Furman and Clemson University, was published in the journal Biology of Sex Differences. The team set out to address two intertwined problems: the persistent excess of severe obesity among women compared with men, and the growing but still murky evidence that the gut microbiome shapes feeding behavior. Individuals with obesity are known to carry an altered gut microbiome, but whether those microbial differences actually drive overeating—or merely accompany it—has remained an open question, particularly with respect to sex differences.

To measure hedonic feeding with real precision, the researchers turned to an approach borrowed from economics rather than simple food-intake counts. Male and female Sprague-Dawley rats were trained in a de-escalating fixed ratio operant task built on behavioral economics principles. In this paradigm, animals work—pressing a lever—to earn high-fat, palatable reward pellets, and the price of those pellets, measured in effort, steadily increases. The design allows researchers to estimate two key parameters. The first is demand elasticity, denoted alpha, which captures how quickly an animal’s demand for the reward falls as the price of obtaining it rises. The second is demand at null cost, or Q0, an extrapolated prediction of how much the animal would consume if the reward required no effort at all. Together, these values describe not just how much an animal eats, but how much it values the food—an economic signature of hedonic drive.

The baseline results were clear and consistent with the team’s earlier work: female rats showed a significantly higher demand at null cost for the high-fat palatable pellets than male rats. In plain terms, when effort was stripped away, females valued and would consume more of the palatable reward than males. Because hedonic feeding is a well-recognized contributor to chronic overconsumption in environments saturated with calorie-dense foods, this kind of sex-linked difference in reward valuation is exactly the sort of biological signal that could help explain why severe obesity disproportionately affects women.

The next question was what might be driving that difference. Emerging evidence suggests the gut microbiome influences feeding behavior through several channels, including the production of short chain fatty acids, metabolites generated when gut bacteria ferment dietary fiber, and through effects on bile acids, molecules synthesized from cholesterol that aid fat digestion and also act as signaling agents in the gut and beyond. The researchers therefore administered an antibiotic cocktail in the rats’ drinking water to disrupt the gut microbiome, then re-ran the behavioral economics task to see whether wiping out the microbial community would change hedonic feeding in either sex.

The outcome was striking in its restraint. Female rats given antibiotics continued to show a higher demand at null cost compared with untreated male control rats, and—critically—the researchers found no statistically significant difference between antibiotic-treated males and females. In other words, disrupting the microbiome did not erase or meaningfully reshape the sex difference in hedonic reward valuation. The antibiotic treatment did do its biological job: when the team characterized the fecal microbiome at the genus level before and after antibiotic administration, they documented clear disruption to the bacterial community, alongside measured changes in fecal short chain fatty acid levels. They also profiled serum short chain fatty acid and bile acid levels at the end of the study, providing a metabolomic snapshot of the systemic consequences of microbial disruption.

What makes the finding conceptually important is what it rules out, or at least renders less likely as a simple explanation. If baseline differences in gut bacterial composition between males and females were the primary engine of the female rats’ stronger hedonic drive, collapsing that composition with antibiotics should have narrowed the gap. It did not. The authors also report that they did not observe striking baseline sex differences in fecal microbiome diversity and composition in the first place, which further weakens the notion that straightforward differences in which bacterial genera dominate the gut could account for the behavioral divergence. The study’s own conclusion is deliberately measured: these results bring into question whether the gut microbiome contributes to sex differences in hedonic feeding at all.

That said, the researchers are careful not to close the book on microbial influence. The gut microbiome is not a single variable but a network of interacting communities and metabolites, and antibiotics are a blunt instrument. The team points to network factors—such as the interplay between the microbiome and bile acids, which themselves show sex differences and can modulate feeding—as avenues requiring further investigation. Serum bile acid profiles measured at the study’s endpoint suggest that downstream signaling pathways, rather than raw bacterial composition, may be where sex-specific microbial effects on appetite ultimately reside, if they exist.

The work also carries a methodological lesson for the field. Behavioral economics approaches like the de-escalating fixed ratio task distinguish between consumption and motivation, two things that simple access-feeding experiments conflate. An animal that eats more of a tasty food at zero cost but gives up quickly when effort increases is economically different from one that persists at high prices, and only the second pattern reflects a genuine shift in reward valuation. By anchoring sex comparisons in demand curve parameters rather than grams consumed, studies of this kind can pinpoint whether the sexes differ in how much they value palatable food, in how sensitive they are to its cost, or both. In this case, the female-male difference lived specifically in the null-cost demand estimate.

For human health, the implications are cautious but meaningful. The finding that female rats place a higher intrinsic value on high-fat palatable food parallels epidemiological patterns in which women face higher rates of severe obesity, and it reinforces the idea that any intervention aimed at curbing pleasure-driven eating may need to account for sex as a fundamental biological variable rather than an afterthought. At the same time, the negative result on the microbiome tempers enthusiasm for microbial therapies—probiotics, targeted antibiotics, or fecal transplants—as quick fixes for hedonic overeating, at least until the relevant mechanisms are better mapped. Obesity, the authors note, remains a pressing public health issue, and hedonic feeding, while not its sole culprit, is one of its major contributing forces. Untangling which biological threads—hormonal, neural, microbial, or metabolic—woven together produce the sex difference in reward valuation will demand the kind of systematic, multi-dimensional profiling this study models: behavior, bacterial census, and metabolites measured in the same animals, before and after perturbation. The microbiome may yet play a role in appetite, but this careful experiment suggests that if it does, it operates through subtler, networked pathways than the simple presence or absence of particular gut bacteria.

Subject of Research: Sex differences in hedonic feeding and the effects of antibiotic-induced gut microbiome disruption in rats

Article Title: Sex differences in hedonic feeding and characterizing the effects of antibiotic-induced microbiome disruption

Article References: Sex differences in hedonic feeding and characterizing the effects of antibiotic-induced microbiome disruption. (n.d.). https://doi.org/10.1186/s13293-026-00970-1

Image Credits: AI Generated

DOI: 10.1186/s13293-026-00970-1

Keywords: hedonic feeding, gut microbiome, sex differences, behavioral economics, obesity, antibiotics, short chain fatty acids, bile acids, operant conditioning, Sprague-Dawley rats, microbiome disruption, food reward