Nature, Calcigender, Nurture: Sex-dependent differential Ca²⁺ homeostasis as the undervalued third pillar

Figures & data

Figure 1. a. General human karyotype. Author: Raj.paljun13 Own work (Created 11/03/2016). Background color has been made less dark than in original. Copyright permission: freely accessible under creative Commons (CC BY-SA 4.0). With thanks to the author. From Wikipedia: Karyotype (human male). [9] b. Ideogram of human chromosome. Chromosome Y highlighted. G-band, 850 bphs (bands per haploid set). Black and gray: Giemsa positive. Red: Centromere. Light blue: Variable region. Dark blue: Stalk National Center for Biotechnology Information, U.S. National Library of Medicine – File created 29 July 2017 NCBI’s Genome Decoration Page. From Wikipedia: Testis Determining Factor. [10] Copyright: Public domain, with thanks. X: X chromosome; Y: Y chromosome; MT: mitochondrial.

Figure 2. a. Barr body, the condensed second X chromosome[17]. Photomicrograph example of normal fibroblast that was FITC-labeled using antisera to histone macroH2A1. Arrow points to sex chromatin site in the FITC-labelled photo. This file, originally published by Gartler et al. [12,13], is licensed under the Creative Commons Attribution 2.0 Generic license. With thanks. b. Location of genes involved in gonadal sex differentiation. The sex-determining region of the Y (SRY) gene codes for the production of the SRY protein, which causes testis differentiation. Absence of this gene in an individual lacking the Y chromosome results in the formation of ovaries. The DAX-1 gene on the X chromosome suppresses SRY gene expression in a rather complex way. Authors: Jones and Lopez 17 with thanks. Copyright permission obtained from Elsevier. c. Image of the SRY protein (in violet) partially inserted in between two DNA strands (in green and yellow). From Wikipedia: Testis-determining factor.10 Copyright permission details: File:PBB Protein SRY image.jpg, Uploaded: 3 January 2010: stated to be public domain from www.pdb.org. With thanks to the non-disclosed author.

Figure 3. The structure of the main sex-steroids testosterone and estradiol, and the general reaction for the conversion of testosterone to estradiol catalyzed by aromatase. Steroids are composed of four fused rings (labeled A-D). Aromatase converts the ring labeled “A” into an aromatic state. From Wikipedia: aromatase. [19] Author Boghog 2 (own work). Public domain, with thanks.

Figure 4. Schematic representation of the main Ca²⁺ gradients in animal cells. From De Loof [7].This figure illustrates that the huge gradients require incessant “efforts” to keep the Ca²⁺ concentration in the cytoplasm at or around a very low concentration of 100 nM. For a more detailed physiological explanation, in particular with respect to the mechanisms indicated by the numbers 1, 2 and 3 see the original Open Access paper[7].

Figure 5. Cartoon illustrating the idea that the main difference between the various gender forms resides in the Ca²⁺-homeostasis system, in particular in some brain areas. Given that the human brain contains about 100 billion nerve cells, it is de facto impossible that two individuals have exactly the same Ca²⁺-homeostasis system in the totality of their brain, even if these two individuals are identical twins. This figure illustrates the commonly observed situation that the sexual thinking and behavior of transgenders reflects more the situation of the other heterosexual somatic sex than their own somatic genetic sex. Between these two depicted extremes, numerous intermediate forms are theoretically possible. Indeed, it is more likely that not the whole brain but specific brain regions can display (subtle) changes in Ca²⁺ homeostasis with effects on behavior as a result. Copied from De Loof [1] (own work), no copyright permission required.

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Wikipedia: Testis determining factor. [cited 2019 January 26]. Available from https://en.wikipedia.org/wiki/Testis-determining_factor

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Wikipedia: Barr body. [cited 2019 January 26]. https://en.wikipedia.org/wiki/Barr_body

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De Loof A. Only two sex forms but multiple gender variants: how to explain? Commun Integr Biol. 2018;e1427399 (15 pp). DOI:10.1080/19420899.2018.1427399

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