The hormone-miRNA axis, life span, and sexual orientation

A Steroid Receptor-MicroRNA Switch Regulates Life Span in Response to Signals from the Gonad in the nematode Caenorhabditis elegans. “…the hormone-miRNA axis coordinates metabolism, maturation, and the relative timing of events between the reproductive system and the soma, with ultimate effects on life span.” Apparently, the “soma” is somewhat akin to the brain of invertebrates and vertebrates.

If steroid receptor-microRNA switches regulate life span in response to signals from the gonads in this model organism (e.g., a worm), do they also regulate sexual orientation in response to signals from the in utero and postnatal sensory environment of mammals? If the molecular mechanisms are conserved from microbes to man, it is likely that the epigenetic effects of nutrient chemicals and pheromones on the microRNA / messenger RNA balance control incalculable interactions among the 4.5 million DNA switches in the human genome. Those interactions appear to determine the development of personal preferences for food, friends, and lovers. Fast forward from the hormone-miRNA axis of Caenorhabditis elegans, for example to the role of the hormone-miRNA axis in epigenetically canalized human sexual development.

See, for review, Homosexuality as a Consequence of Epigenetically Canalized Sexual Development Summary: Fifty years of  research on androgen-dependent sexual development now incorporates the term “epi-marks ” that alter the hormone-miRNA axis and sexual orientation via changes in chromatin structure that influence the transcription rate of genes including nucleosome repositioning, DNA methylation, and/or modification of histone tails.

For a meaningful lay version of the above information see: Homosexuality May Start in the Womb by Elizabeth Norton

Excerpt: “… the authors propose that differences in sensitivity to sex hormones result from “epigenetic” changes. These are changes that affect not the structure of a gene but when, if, and how much of it is activated—by chemically altering a gene’s promoter region or “on” switch, for example.”

Colleagues and I first approached the molecular epigenetics of sexual orientation in our 1996 Hormones and Behavior paper. From fertilization to adult sexual behavior. Excerpt, sans incorporated references:

“Yet another kind of epigenetic imprinting occurs in species as diverse as yeast, Drosophila, mice, and humans and is based upon small DNA-binding proteins called “chromo domain” proteins, e.g., polycomb. These proteins affect chromatin structure, often in telomeric regions, and thereby affect transcription and silencing of various genes. Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans. That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.”

Instead of simply offering more evolutionary theory, we detailed the link from the sensory environment to sexual orientation (e.g., the epigenetic effects of pheromones on the gonadotropin releasing hormone neuronal system). There are many more details in our review article, and most have been ignored to favor theories about adaptively evolved behavior that have never “fit” what is known about systems biology (back then, or now). Shall we continue to wait for sexologists and theorists to fit what is neuroscientifically known into their misrepresentations of it? I think that more scientific progress could have been made, at least since 1996, if others had taken to heart the message “…that some human sex differences may arise from alternative splicings of otherwise identical genes.” That message is coming through loud and clear now, isn’t it? See for example: Evolution by Splicing.

One of the more interesting aspects of our 1996 paper was a comment that originated with co-author TB: “Parenthetically it is interesting to note even the yeast Saccharomyces cerevisiae has a gene-based equivalent of sexual orientation (i.e., a-factor and alpha-factor physiologies). These differences arise from different epigenetic modifications of an otherwise identical MAT locus.”

There are now clearer indications that those epigenetic modifications in the MAT locus are nutrient chemical-dependent (e.g., glucose-dependent). It also seems apparent that subsequent alterations in the hormone-miRNA axis in vertebrates and invertebrates alter the miRNA/messenger RNA balance that controls intracellular homeostasis. Intracellular homeostasis controls species-specific individual and group homeostasis because perturbations cause ecological, social, neurogenic, and socio-cognitive niche construction. The four stages of niche construction are required for us to associate our sexual orientation and longevity with the epigenetic effects of glucose on gonadotropin releasing hormone pulse frequency. Other animals cannot associate their sexual orientation and longevity with anything. Their niches are not constructed in a manner that allows them to think about much of anything except perhaps food acquisiton and reproduction. Arguably, however, they think about such things nearly as much as most people do, which is not at all,  despite their evolved socio-cognitive niches.


About James V. Kohl 1308 Articles
James Vaughn Kohl was the first to accurately conceptualize human pheromones, and began presenting his findings to the scientific community in 1992. He continues to present to, and publish for, diverse scientific and lay audiences, while constantly monitoring the scientific presses for new information that is relevant to the development of his initial and ongoing conceptualization of human pheromones. Recently, Kohl integrated scientific evidence that pinpoints the evolved neurophysiological mechanism that links olfactory/pheromonal input to genes in hormone-secreting cells of tissue in a specific area of the brain that is primarily involved in the sensory integration of olfactory and visual input, and in the development of human sexual preferences. His award-winning 2007 article/book chapter on multisensory integration: The Mind’s Eyes: Human pheromones, neuroscience, and male sexual preferences followed an award winning 2001 publication: Human pheromones: integrating neuroendocrinology and ethology, which was coauthored by disinguished researchers from Vienna. Rarely do researchers win awards in multiple disciplines, but Kohl’s 2001 award was for neuroscience, and his 2007 “Reiss Theory” award was for social science. Kohl has worked as a medical laboratory scientist since 1974, and he has devoted more than twenty-five years to researching the relationship between the sense of smell and the development of human sexual preferences. Unlike many researchers who work with non-human subjects, medical laboratory scientists use the latest technology from many scientific disciplines to perform a variety of specialized diagnostic medical testing on people. James V. Kohl is certified with: * American Society for Clinical Pathology * American Medical Technologists James V. Kohl is a member of: * Society for Neuroscience * Society for Behavioral Neuroendocrinology * Association for Chemoreception Sciences * Society for the Scientific Study of Sexuality * International Society for Human Ethology * American Society for Clinical Laboratory Science * Mensa, the international high IQ society