June 10, 2022 | Jerry Bergman

Genetic Sex Runs Deep

As research progresses, differences between men
and women are seen to increase. Genetic sex determines
muscle communications with other body organs.


by Jerry Bergman, PhD

The more scientists learn about the human body, the more complex we realize it is. As shown below, this increased understanding of our bodies also highlights the contrasts between the sexes, and raises issues about trying to change one to the other.

A new study by Marcus M. Seldin, Ph.D., Assistant Professor of Biological Chemistry at UCI (University of California, Irvine) School of Medicine, determined that genetics influences hormone production, especially estrogen, which, in turn, influences muscle signaling to other body tissues.[1] The researchers concluded that “sex-specific circuits of muscle” send signals to other tissues and the signals’ impact is “markedly different between males and females.”[2] Here is another example that undermines the once-common belief that males and females only differ in plumbing.[3]

The authors were not trying to document another difference between males and females. Rather, they wanted to explore the causes and treatments of chronic diseases such as obesity, type-2 diabetes, and cardiovascular disease. Muscle health is critical for maintaining the required metabolic level for good health; disruption of this muscle function is an important contributor to those chronic conditions. Knowing this, consider what happens during cardiovascular exercise.

Walk for Health

Cardio exercise has different effects on males and females.

An obvious activity for maintaining muscle communication involves exercise – particularly walking. Cardiovascular activity such as walking helps reduce the symptoms of obesity and type-2 diabetes, and can ameliorate cardiovascular disease. The advantages of walking include the following:

  • It lowers the risk of heart disease, stroke, diabetes, and cancer, including breast cancer.
  • It improves circulation and blood flow to the entire body, and burns calories to reduce weight gain and, as a side effect, it helps prevent constipation.
  • It releases stress reducing hormones that help to control blood-sugar levels for up to 24 hours. This helps to reduce the risk of diabetes while keeping energy levels stable throughout the day.
  • It helps keeps the mind sharp and reduces the risk of Alzheimer’s disease and dementia.
  • It also boosts the immune system, improves sleep quality, reduces pain levels, and helps to manage arthritis symptoms.
  • It helps to maintain eyesight and avoid cataracts as a result of  improved circulation.
  • It even reduces the risk of periodontal disease.

Walking can also help the body to learn how to utilize fat more efficiently as an energy source. Walking is a weight-bearing activity that can be very beneficial in reducing osteoporosis. It also keeps the spine healthy because walking motion is vital to nutrient exchange in the spinal discs.[4]

Myokines in muscle cells send signals that cause sex differences in all organs of the body.

Genetic Sex Matters

These benefits are all very well documented medically. The goal of the current study was to understand the role of sex hormones in myokine signaling.[5] Myokines are cytokines (proteins that affect other cells like hormones) that are synthesized and released by skeletal muscles during activities such as walking, which involve muscular contractions. Cytokines (cyto = cell + kinesis = movement) are peptides that cannot cross the cell’s lipid bilayer to enter the cell cytoplasm. Rather, they function by interacting with cell-surface receptors.[6] Myokines are cytokines that regulate muscle-cell growth, proliferation, and differentiation. As the researchers explained, all skeletal muscles secrete myokines

which play roles in a variety of processes by interacting with other tissues. Essentially, myokines allow skeletal muscles to communicate with organs such as the kidneys, the liver or the brain, which is essential for the body to keep its metabolic balance. Some of the process myokines are involved with include inflammation, cancer, the changes brought about by exercise, and even cognition. Despite the clear relevance of myokines to so many physiological outcomes, the way these proteins are regulated and their effects are not well understood.[7]

This is important because “Skeletal muscle plays an integral role in coordinating physiological homeostasis, where signaling to other tissues via myokines allows for coordination of complex [body] processes.”[8] The UCI study found that sexual differences have a profound effect on many of these body processes. The study concluded that

nearly all significant cross-tissue enrichments operated in a sex-specific or hormone-dependent fashion; in particular, with estradiol [a pharmaceutical preparation of the female hormone estrogen]. These sex- and hormone-specific effects were consistent across key metabolic tissues: liver, pancreas, hypothalamus, intestine, heart, visceral, and subcutaneous adipose tissue.[9]

Sex differences appear in every organ and cell.

Consequently, as a result of the disparate influence of myokines in males and females, sexual differences can be detected in numerous body organs: the liver, pancreas, hypothalamus, intestine, heart, and more throughout the viscera. One externally obvious difference concerns the position and level of subcutaneous adipose tissue between men and women, but other “sex-dependent mechanisms of myokine signaling were uncovered” too, including

muscle-derived tumor necrosis factor alpha (TNFA) enriched for stronger inflammatory signaling in females compared to males and GPX3 as a male-specific link between glycolytic fiber abundance and hepatic inflammation… sex and estradiol receptor signaling as critical variables when assaying myokine functions and how changes in cell composition are predicted to impact other metabolic organs.[10]

Importantly, myokines are only one of several hundred different kinds of cytokines and proteoglycan peptides produced by skeletal-muscle cells in response to muscular contractions.[11]

Consequences of sexual transitioning attempts

Among the many concerns that this research raises is the so-called ‘transitioning process’ gaining popularity among young people questioning their gender identity. Popular culture is pushing many who feel dissatisfied with their looks to think they may have been “born in the wrong body.” Some medical institutions are rising up to help affirm the new “transsexuals” claim their newfound “gender identity” with hormonal treatment and surgery. But is it possible to convert males to females and females to males to satisfy this new fad?

Pharmaceutical-grade estradiol is used in attempting to convert males to females. This hormone is responsible for the development of secondary sexual characteristics and bodily features that develop during puberty including breast development, body shape changes (wide hips for child delivery), bone growth, and female fat deposition. The effects of long-term administration of this powerful hormone to transition are unknown, and will be unknown until the necessary length of the follow-up time has elapsed.

Possible consequences of the rush to transition could be severe. Despite the clear role of myokines in causing many different physiological outcomes, the “way these proteins are regulated and their effects are not well understood.”[12] Thus, this long-term transition experiment could cause serious damage to one or more organs. As the UCI study shows, sex differences run deep. Sex change operations and hormone therapies used in ‘transitioning’ are essentially nothing more than chemical cosmetic surgery. They are attempts to change the appearance; they do not make a female from a male or vice versa (see my 27 May 2022 article).

One species but two sexes: male-female differences run deep. (Credits: left: David Rives channel. Right: Alma Deutscher channel.)


As we learn more about the details of the anatomy and physiology of the human body, we should be considered about the rush to assist unhappy people change their gender. It will likely cause major regrettable health problems down the road. This study corroborates my long-term opinion, based on many years teaching biology and genetics, that gender dysphoria requires a psychologist – not a surgeon. The UCI study states one of their major conclusions:

many of the metabolic traits impacted by myokines show striking differences arising from hormonal or genetic interactions depending on the genetic sex of the subject being studied. It is therefore important to consider genetic sex when studying the effects of myokines on the body.[13]

Ed. note: Each sex/gender has its advantages and disadvantages. Instead of cultivating dissatisfaction and envy, which can infect all areas of life, why not help the young embrace the advantages of their biological sex? Learning gratitude cures many a dysphoria (malaise, discomfort). A good resource for counseling people caught up in gender dysphoria is Nancy Pearcey’s book, Love Thy Body.

Note also that Bergman’s article concerns normal males with XY chromosomes and normal females with XX chromosomes. The University of Cambridge reported today (10 June 2022) that 0.2% of males have an extra X or Y chromosome, and this abnormality puts them at higher risk of several common diseases. While some of the males appear normal and are able to live normal lives, the full impact of these genetic abnormalities (XXY and XYY males) are not fully understood: “The researchers say that it isn’t clear why an extra chromosome should increase the risk or why the risks were so similar irrespective of which sex chromosome was duplicated.”


[1] UCI School of Medicine. New UCI-led study finds that your genetic sex determines the way your muscle “talks” to other tissues in your body, 31 May 2022; https://www.som.uci.edu/news_releases/genetic_sex_determines_way_muscle_talks.asp.

[2] UCI School of Medicine, 2022.

[3] Dickey, John W. The Public Administration (P.A.) Genome Project Capturing, Mapping, and Deploying the “Genes” of P.A. Information Age Publishing: Charlotte, NC, 2009, p. 49.

[4] The Physical Therapy Advisor. Why Walking is Critical for Your Health; https://www.thephysicaltherapyadvisor.com/2015/06/10/why-walking-is-critical-for-your-health/, 10 June 2015.

[5] Velez, Leandro M., et al. Genetic variation of putative myokine signaling is dominated by biological sex and sex hormones; https://elifesciences.org/articles/76887, 11 May 2022.

[6] Lackie, John. “Cytokines.” A Dictionary of Biomedicine. Oxford University Press: New York, NY, 2010.

[7] Velez, et al., 2022.

[8] Velez, et al., 2022.

[9] Velez, et al., 2022.

[10] Velez, et al., 2022.

[11] Pedersen, Bente Klarlund, et al. Role of myokines in exercise and metabolism. Journal of Applied Physiology 103(3):1093–1098; doi:10.1152/japplphysiol.00080.2007. PMID 17347387, 1 September 2007.

[12] Velez, et al., 2022.

[13] Velez, et al., 2022, bold added.

Dr. Jerry Bergman has taught biology, genetics, chemistry, biochemistry, anthropology, geology, and microbiology for over 40 years at several colleges and universities including Bowling Green State University, Medical College of Ohio where he was a research associate in experimental pathology, and The University of Toledo. He is a graduate of the Medical College of Ohio, Wayne State University in Detroit, the University of Toledo, and Bowling Green State University. He has over 1,300 publications in 12 languages and 40 books and monographs. His books and textbooks that include chapters that he authored are in over 1,500 college libraries in 27 countries. So far over 80,000 copies of the 40 books and monographs that he has authored or co-authored are in print. For more articles by Dr Bergman, see his Author Profile.

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