Epigenetic control of GnRH neurons
Abstract (free full text):
Epigenetic modifications to the genome, including DNA methylation and histone modifications, occur in response to external stimuli. Reproductive function is highly sensitive to environmental conditions including season, diet, hormonal changes, and exposure to chemical contaminants. GnRH neurons, which play a key role in reproduction, are particularly sensitive to various environmental stimuli. We recently reported that the rhesus monkey GnRH gene exhibits distinct epigenetic differentiation during embryonic development. More recently, we further found that a similar epigenetic phenomenon occurs across puberty. In this article, we highlight recent findings, suggest implications of these findings (or potential mechanisms) and then discuss current challenges as well as future work. Consequently, this review will provide background to understand the epigenetic control of GnRH neurons as a link between the environment and reproductive function.
My comment:
Re: “…an understanding of GnRH neuron biology and the means by which an environment modifies neuronal function (i.e., epigenetic modifications), lies at our fingertips.”
There is a model of how olfactory/pheromonal input from the sensory environment epigenetically modifies GnRH neuronal function. The model incorporates the thermodynamics of intracellular signaling and organism-level thermoregulation with examples of conserved molecular mechanisms in model organisms. The examples link the epigenetic landscape to the physical landscape of DNA, which is required for adaptive evolution to occur via ecological, social, neurogenic, and socio-cognitive niche construction in species from microbes to man. See for example: Kohl, J.V. (2013) Nutrient-dependent/pheromone-controlled adaptive evolution: a model. Socioaffective Neuroscience & Psychology, 3: 20553.
This model first incorporated molecular epigenetics in our 1996 Hormones and Behavior review article: From Fertilization to Adult Sexual Behavior, which led to publication of an award-winning review on the development of heterosexual attraction and use of the same model to explain the development of homosexual orientation in another award-winning review/book chapter. Elekonich and Robinson extended our model of epigenetically effected hormone-organization and hormone activation to insects in 2000, and to life history transitions in the honeybee model organism in 2005.
Other model organisms refute every aspect of random mutations theory by showing that behavioral development is nutrient-dependent and pheromone-controlled in species from microbes to man. For example, the molecular mechanisms are conserved, which refute comments by LeVay on the model.
p. 210 – 211 “Still, even in fruit flies, other sensory input besides pheromones — acoustic, tactile, and visual stimuli — play a role in sexual attraction, and sex specific responses to these stimuli appear to be innate rather than learned by association [36.]. We simply don’t know where the boundary between prespecified attraction and learned association lie in our own species, nor do we have compelling evidence for the primacy of one sense over another.”
The epigenetically-effected GnRH response is innate in mammals, and so is the response to food odors and pheromones in species from microbes to man. Responses to other sensory input are learned via associations with olfactory/pheromonal input. The compelling evidence for the primacy of olfactory/pheromonal input and its epigenetic effect on GnRH has always been found in the conserved molecular mechanisms of every species on the planet.
The conserved molecular mechanisms of chromatin remodeling allow the epigenetic landscape to become the physical landscape of DNA, as indicated in the article on Epigenetic control of GnRH neurons and in the examples I included in Kohl, J.V. (2013) Kohl, Nutrient-dependent/pheromone-controlled adaptive evolution: a model. The examples include adaptive evolution of a human population that arose in central China during the past ~30K years due to a single base pair alteration that resulted in a single amino acid substitution and morphogenic changes in teeth, hair, eccrine sweat glands, and the mammary (e.g., apocrine glands). Those changes are associated with sexual selection for nutrient-dependent species-specific pheromone production. Sexual selection for pheromones also occurs in moths, scented apes, and other species that sexually reproduce (i.e., all of them). Pheromones control reproduction in all species, whether or not they sexually reproduce.
James V. Kohl detailedl how quantized energy-dependent microRNA biogenesis links the pheromone-controlled physiology of reproduction to biophysically constrained viral latency and healthy longevity. Links from what organisms eat to the enzyme-dependent metabolism of food also link metabolic networks to microRNA-mediated genetic networks in the context of RNA interference. Drug therapies alter RNA interference by altering cell type differentiation in all cells of all individuals of all species. For comparison, during the past 26 years, Kohl has detailed how the chemistry of protein folding is biophysically constrained at every level of biological organization by conserved molecular mechanisms.