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Hormonal Regulatory Networks in Aging, Cancers, Alzheimer’s Disease, and Therapeutics

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 120

Special Issue Editor


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Guest Editor
Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
Interests: aging and comorbidities; hormone regulation and function; endocrine physiology and pathophysiology; signal transduction pathways; steroidogenesis; hormonal alterations in aging; tumorigenesis; genetics and epigenetics; immunomodulation; neurodegenerative processes; therapeutic strategies
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Special Issue Information

Dear Colleagues,

The maintenance of bodily homeostasis is contingent on the appropriate functioning of a wide range of hormones. A hallmark of healthy physiology is the ability to sense, respond to, and control innumerable processes, in which hormones play indispensable roles. Dysregulation of hormonal stability, including sex hormones and neurosteroids, is a primary cause of human senescence, resulting in a variety of health complications and diseases. Aging is an unavoidable heterogeneous phenomenon involving the whole organism in which the structural and functional efficacies of a multitude of organs are deteriorated and results in endocrino-immuno-senescence. Disruption of age-associated hormonal equilibrium involves the hypothalamic-pituitary-gonadal axes (hypogonadism), estrogen and progesterone (menopause), testosterone (andropause), and dehydroepiandrosterone and its sulfate (adrenopause), which profoundly affect geriatric populations worldwide. The manifestations of hormonal/steroidal deficiencies include, but are not limited to, diminished eyesight, impaired memory and cognitive function, decreased muscle mass and bone density, sexual dysfunction and depression, increased risk of cardiovascular diseases (CVDs), and skin disorders, which modulate the immune system and contribute to increased morbidity and mortality. Moreover, aging is the primary risk factor for diverse pathologic events, especially hormone-sensitive breast and other relevant malignancies, in addition to neurodegenerative diseases, exclusively the most prevalent Alzheimer’s disease. These age-dependent diseases are also impacted by immunocompromised conditions, including diabetes, obesity, and CVDs. Whereas a number of therapeutic approaches have evolved for countering a host of pathological processes during aging, preservation of hormonal balance is pivotal for sustaining several activities. Hence, the improvement of physical function and mobility and the restoration of hormone insufficiencies in continuously growing aging populations are pivotal for healthy aging and the quality of life of elderly women and men.

This Special Issue is aimed at publishing original research and review articles that address recent advances and understanding of fundamental, cellular, and molecular events involved in hormonal networks in aging, relevant diseases, and therapeutics.

Dr. Pulak R. Manna
Guest Editor

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Keywords

  • hormonal imbalance and aging
  • endocrinology
  • physiology and pathophysiology
  • steroidogenesis
  • sex hormones and neurosteroids
  • age-related complications and diseases
  • tumorigenesis
  • hormone-dependent cancers
  • neurodegenrative diseases
  • Alzheimer’s disease
  • therapeutics
  • healthy aging

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Published Papers (1 paper)

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Review

23 pages, 1432 KB  
Review
The Sex Hormone Precursors Dehydroepiandrosterone (DHEA) and Its Sulfate Ester Form (DHEAS): Molecular Mechanisms and Actions on Human Body
by Hsin-Yi Lin, Jie-Hong Chen and Kuo-Hu Chen
Int. J. Mol. Sci. 2025, 26(17), 8568; https://doi.org/10.3390/ijms26178568 - 3 Sep 2025
Abstract
Dehydroepiandrosterone (DHEA) and its sulfate ester form DHEAS, are multifunctional steroid hormones primarily produced in the adrenal cortex, with additional synthesis in peripheral tissues. DHEA/DHEAS serve as precursors to sex steroids and exhibit neuroprotective, anti-inflammatory, and immune-modulating effects. DHEA levels decline significantly with [...] Read more.
Dehydroepiandrosterone (DHEA) and its sulfate ester form DHEAS, are multifunctional steroid hormones primarily produced in the adrenal cortex, with additional synthesis in peripheral tissues. DHEA/DHEAS serve as precursors to sex steroids and exhibit neuroprotective, anti-inflammatory, and immune-modulating effects. DHEA levels decline significantly with age, a phenomenon termed “adrenopause,” prompting interest in supplementation to mitigate age-related symptoms. Particularly in postmenopausal women, DHEA has shown potential benefits in treating genitourinary syndrome of menopause (GSM), including improved vaginal health, lubrication, and sexual function. While intravaginal DHEA appears effective and safer than systemic estrogen therapy, especially for women with estrogen sensitivity, results remain mixed for oral administration. DHEA and DHEAS exhibit diverse neuroactive properties through modulation of GABA-A, NMDA, and sigma-1 receptors. These neurosteroids contribute to neuroprotection, synaptic plasticity, and mood regulation. Altered DHEA/DHEAS levels have been implicated in neurodegenerative disorders and depression, with emerging evidence supporting their potential therapeutic value. In addition, DHEA plays a multifaceted role in aging-related physiological changes. It supports muscle anabolism, bone density maintenance, cardiovascular protection, and immune regulation. Though supplementation shows potential benefits, especially in conjunction with resistance training, results remain discrepant. Current evidence has revealed that the therapeutic effects of DHEA supplementation are inconsistent in different human systems among different studies. The diversity of results is mainly due to heterogeneous receptor distribution, various action pathways, and distinct tissue responses in different systems. Further research is needed to define its efficacy and dosage across various systems. Full article
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