There’s a model for that!

Neuroscientists reveal mechanism crucial to molding male brains

Excerpt 1) “…sex differences in brain function are established during the later stages of foetal development and around birth, but the actual cellular mechanisms underlying these important actions remained unknown.”

My comment: In our 1996 Hormones and Behavior review we provided details about how these cellular mechanisms link sex differences in brain function, which are established during the later stages of fetal development, to the sex differences that are established perinatally. We linked small intranuclear proteins to alternative splicing techniques of pre-mRNA that contribute to sexual differentiation in flies and nematodes to proteins that perform similar functions in humans, which “…suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.”

Excerpt 2) “…a small group of GnRH neurons in the brain’s hypothalamus become active only in new-born males, and not females.”

My comment: That fact links the molecular epigenetics of sex differences in cell types from yeasts to human new-borns via conserved molecular mechanisms of RNA-mediated cell type differentiation. Cell type differentiation is nutrient-dependent and pheromone-controlled. Nutrient uptake is essential to RNA-mediated gene duplication. Fixation of nutrient-dependent amino acid substitutions is controlled by the metabolism of nutrients to species-specific pheromones. The pheromones control the physiology of nutrient-dependent reproduction, which is how the population-wide fixation of amino acid substitutions that differentiate cell types occurs.

See: Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors

The forthcoming report from Herbison’s group will no doubt report something similar to this:

Excerpt: “Within minutes of birth, there is also a genetically predisposed, sexually differentiated, GnRH-directed, luteinizing hormone (LH) response in mammalian males, but not in females (Grumbach & Styne, 1992). Activation of the male’s LH response involves GnRH (Hoffman, Lee, Attardi, Yann, & Fitzsimmons, 1990), and the GnRH-directed LH response to female pheromones is linked to increased testosterone (T) secretion in the males of many different species (Nyby, 2008).

In mammalian males, the LH response at birth appears to be caused by pheromones associated with food odors emanating from the mother’s nipple (Schaal et al., 2009; Schaal, Doucet, Sagot, Hertling, & Soussignan, 2006). Other sensory input and its integration also may be associated with the male’s LH and T response throughout life.”

[They may not link the response to any other animal models.]

“But the pheromones of a mammalian mother, like those of the honeybee queen, are the only known direct causal link from a sensory stimulus to an immediate hormone response in the brain of male mammals that does not occur with parturition in female mammals.”

[They are not likely to link the response to human pheromones]

“Sex differences in the effects of pheromones

The GnRH-directed LH and T response in the male is linked to rapid remodeling of the male infant’s brain that occurs during the first postnatal 6 months, particularly in areas associated with cognitive tasks, including spatial conceptualization and the emotional processing of visual cues (Sanai et al., 2011). This remodeling of the brain appears to continue throughout life. GnRH and LH cause subsequent changes in levels of other hormones associated with sexual differentiation of the brain and with behavior (see for review, Wizemann & Pardue, 2001).

Maternal pheromones that initiate these changes could effectively continue to rewire the developing male brain during the next 6–8 months. This would allow for male and female differences in the developing brain that extend to the next 2–3 years (Sanai et al., 2011).”

[If they do not link the human response to pheromones, researchers may continue to miss the link to the honeybee model organism]

“These effects of pheromones on hormones potentially extend the honeybee model for experiential conditioning of hormone-mediated changes in the honeybee brain to sex differences in the mammalian brain. Affects of pheromones on mammalian behavior incorporate the hypothalamic GnRH pulse generator as the most likely neurophysiological mechanism (Krsmanovic, Hu, Leung, Feng, & Catt, 2009). Positive social interactions associated with pheromones across the organism’s lifespan seem to serve as secondary reinforcers that take on the attributes of primary food rewards essential to survival (Jones et al., 2011).”

[Elekonich and Robinson (2000) linked our 1996 review of hormone-organized and hormone-activated behavior to insects]

[Elekonich and Roberts (2005) linked our 1996 review of hormone-organized and hormone-activated behavior to life history transitions in the honeybee model organism.]

From Kohl (2012)

“This mammalian model for the development of food preferences and social preferences, which incorporates the effects of nutrition and pheromones on hormones that affect behavior, has clear phylogenetic parsimony. Simply put, throughout the life of individuals, the unique experiences of males and females with food odors and pheromones cause the development of preferences for the physical characteristics of food. These unique experiences also cause preferences for the physical characteristics of potential mates.”

The clear phylogenetic parsimony of our 1996 model detailed in the context of Kohl (2012) led to this conclusion: “Olfaction and odor receptors provide a clear evolutionary trail that can be followed from unicellular organisms to insects to humans (Keller et al., 2007; Kohl, 2007; Villarreal, 2009; Vosshall, Wong, & Axel, 2000).” That conclusion was almost completely ignored until long after publication of Nutrient-dependent/pheromone-controlled adaptive evolution: a model. In that 2013 review I linked nutrient-dependent pheromone-controlled amino acid substitutions to cell type differentiation and to morphological and behavioral phenotypes in species from microbes to man.

To his credit, Herbison’s group had already clarified in 2011 the fact that frequency-dependent release of amino acid and neuropeptide transmitters occurs in the context of GnRH release in the mammalian CNS. See: Frequency-Dependent Recruitment of Fast Amino Acid and Slow Neuropeptide Neurotransmitter Release Controls Gonadotropin-Releasing Hormone Neuron Excitability

Excerpt: “The majority of GnRH neurons in the rPOA receive direct, monosynaptic inputs from AVPV neurons, and low-frequency (<1 Hz) stimulation of these inputs evokes an almost exclusive amino acid-mediated regulation of GnRH neuron excitability.”

The forthcoming report should extend my model of nutrient-dependent RNA-directed DNA methylation and RNA-mediated events linked to cell type differentiation via amino acid substitutions to the amino acid-mediated regulation of GnRH neuron excitability. This will link the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man. It will also link the entirety of nutrient-dependent pheromone-controlled HPG axis and HPA axis modulation of cell type differentiation in all cells of all organisms of all species in which GnRH is essential to the physiology of reproduction. If the connection from food odors and pheromones to GnRH is not mentioned, it could be another 18 years, or more, until evolutionary ecologists again revise their timelines. Until then, they may continue to report their results in terms of mutations and/or natural selection that somehow leads to the evolution of what are obviously nutrient-dependent pheromone-controlled morphological and behavioral phenotypes.

Evolutionary theorists seem unable to understand the fact that olfactory/pheromonal input links the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man.  Until they realize that mutations are linked only to diseases and disorders, they may not make the connection between experience-dependent de novo creation of olfactory receptor genes associated with sex differences in morphological and behavioral phenotypes in human infants, adolescents, and adults. Nevertheless, there is a model for that!

Minimally, this model can be compared to any other factual representations of epigenesis and epistasis for determination of the best scientific ‘fit’. (Kohl, 2013) Hopefully, Herbison’s group will not continue to ignore the model.

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