PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
The Purpose of Adrenarche Is Tumor Suppression: Identification of a Novel, Human-Specific, Kill-Switch Tumor Suppression Mechanism Dependent upon the Dramatic Adrenarchal Rise of Adrenal Androgens
Version 1
: Received: 12 April 2023 / Approved: 12 April 2023 / Online: 12 April 2023 (07:38:17 CEST)
Version 2
: Received: 12 April 2023 / Approved: 13 April 2023 / Online: 13 April 2023 (05:01:41 CEST)
How to cite:
Nyce, J.W. The Purpose of Adrenarche Is Tumor Suppression: Identification of a Novel, Human-Specific, Kill-Switch Tumor Suppression Mechanism Dependent upon the Dramatic Adrenarchal Rise of Adrenal Androgens. Preprints2023, 2023040253. https://doi.org/10.20944/preprints202304.0253.v1
Nyce, J.W. The Purpose of Adrenarche Is Tumor Suppression: Identification of a Novel, Human-Specific, Kill-Switch Tumor Suppression Mechanism Dependent upon the Dramatic Adrenarchal Rise of Adrenal Androgens. Preprints 2023, 2023040253. https://doi.org/10.20944/preprints202304.0253.v1
Nyce, J.W. The Purpose of Adrenarche Is Tumor Suppression: Identification of a Novel, Human-Specific, Kill-Switch Tumor Suppression Mechanism Dependent upon the Dramatic Adrenarchal Rise of Adrenal Androgens. Preprints2023, 2023040253. https://doi.org/10.20944/preprints202304.0253.v1
APA Style
Nyce, J.W. (2023). The Purpose of Adrenarche Is Tumor Suppression: Identification of a Novel, Human-Specific, Kill-Switch Tumor Suppression Mechanism Dependent upon the Dramatic Adrenarchal Rise of Adrenal Androgens. Preprints. https://doi.org/10.20944/preprints202304.0253.v1
Chicago/Turabian Style
Nyce, J.W. 2023 "The Purpose of Adrenarche Is Tumor Suppression: Identification of a Novel, Human-Specific, Kill-Switch Tumor Suppression Mechanism Dependent upon the Dramatic Adrenarchal Rise of Adrenal Androgens" Preprints. https://doi.org/10.20944/preprints202304.0253.v1
Abstract
Adrenarche is a developmental phase that occurs only in humans and chimpanzees. It is characterized by the maturation of the adrenal zona reticularis, culminating in the synthesis and secretion of enormous amounts of dehydroepiandro-sterone sulfate (DHEAS) into the blood stream. The purpose of adrenarche, and the flooding of the circulation with DHEAS in the period preceding the onset of adult human body size, has been described as “enigmatic.” This laboratory has uncovered a previously unknown, human-specific “kill-switch” tumor suppression mechanism in which circulating DHEAS is pumped into cells that have undergone tumorigenic mutation(s)— primarily in the TP53 tumor suppressor gene. We refer to such tumorigenic single cells as singularities. The advantage of eliminating tumorigenic cells while they are still in their single cell state, before they have evolved into the heterogeneous tumor cell populations that have proven refractory to chemotherapeutic sterilization, is obvious. This is accomplished by activation of the kill-switch in singularities by de-sulfating imported DHEAS to dehydroepiandrosterone (DHEA), a potent uncompetitive inhibitor of the enzyme Glucose-6-phosphate Dehydrogenase (G6PD). G6PD is responsible for the production of most of the NADPH required for the synthesis and maintenance of activity of anti-oxidant selenoproteins, and for the ubiquinol that prevents ferroptosis. In singularities, uncompetitive inhibition of G6PD by DHEA rapidly becomes irreversible, leading to ROS/ferroptosis-mediated cell death.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.