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Hormonal Diversity: From Organogenesis to Neurodegeneration

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: 20 December 2024 | Viewed by 457

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,

Hormones control numerous processes in the body, including growth and development, reproduction, metabolism, and internal milieu or homeostasis. Regulation of the hypothalamic–pituitary–thyroid–adrenal–gonadal (HPTAG) auto regulating axis, involving a well-balanced endocrine circadian rhythmicity, is crucial to bodily homeostasis, and thus the appropriate development and function of a multitude of organs facilitating healthy physiological activities. Disruption in the HPTAG system, involving the structural and functional efficacies of all organs, affects the central nervous system and the endocrine system, resulting in a decline in various hormones. Hormone deficiencies modulate the immune system, develop an array of physiological anomalies, ranging from carcinogenesis to neurodegeneration, and contribute to increased morbidity and mortality. The majority of these conditions profoundly affect geriatric populations. Senescence is the hallmark of aging that is triggered by numerous factors and/or events, including epigenetic dysregulation, DNA damage, and dysfunction in mitochondrial network, which eventually links to a wide variety of health complications and diseases. Aging is also associated with a host of pathologies, including cancers (both hormone dependent and independent), cardiovascular diseases, and neurodegenerative disorders connecting cognitive impairment and dementia, many of which are particularly influenced by immunocompromised conditions. Therapeutic strategies, involving vitamins and nutrients, facilitating and/or reversing hormonal equilibrium/homeostasis and/or immunomodulation towards younger levels, are the prerequisite for healthy living and/or aging.

This Special Issue of hormonal diversity on a variety of physiological, as well as pathophysiological, aspects provides a venue for publishing both original research and review articles that enhance our in-depth understanding of fundamental cellular and molecular mechanisms in health and diseases.

Dr. Pulak R. Manna
Guest Editor

Manuscript Submission Information

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Keywords

  • hormone regulation and function
  • physiologic events
  • HPTAG auto regulating system
  • bodily homeostasis
  • hormonal imbalance
  • hormone dysregulation and pathophysiology
  • vitamins and healthy aging
  • age-related diseases
  • cancers
  • immunocompromised conditions
  • neurodegenerative disorders

Published Papers (1 paper)

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Research

15 pages, 1927 KiB  
Communication
Acetylation of Steroidogenic Acute Regulatory Protein Sensitizes 17β-Estradiol Regulation in Hormone-Sensitive Breast Cancer Cells
by Pulak R. Manna, Deborah Molehin, Ahsen U. Ahmed, Shengping Yang and P. Hemachandra Reddy
Int. J. Mol. Sci. 2024, 25(16), 8732; https://doi.org/10.3390/ijms25168732 (registering DOI) - 10 Aug 2024
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Abstract
An imbalance in estrogen signaling is a critical event in breast tumorigenesis. The majority of breast cancers (BCs) are hormone-sensitive; they majorly express the estrogen receptor (ER+) and are activated by 17β-estradiol (E2). The steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step [...] Read more.
An imbalance in estrogen signaling is a critical event in breast tumorigenesis. The majority of breast cancers (BCs) are hormone-sensitive; they majorly express the estrogen receptor (ER+) and are activated by 17β-estradiol (E2). The steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in steroid biosynthesis. The dysregulation of the epigenetic machinery, modulating E2 levels, is a primary occurrence for promoting breast tumorigenesis. StAR expression, concomitant with E2 synthesis, was reported to be aberrantly high in human and mouse hormone-dependent BC cells compared with their non-cancerous counterparts. However, the mechanism of action of StAR remains poorly understood. We discovered StAR as an acetylated protein and have identified a number of lysine (K) residues that are putatively acetylated in malignant and non-malignant breast cells, using LC-MS/MS (liquid chromatography–tandem mass spectrometry), suggesting they differently influence E2 synthesis in mammary tissue. The treatment of hormone-sensitive MCF7 cells with a variety of histone deacetylase inhibitors (HDACIs), at therapeutically and clinically relevant doses, identified a few additional StAR acetylated lysine residues. Among a total of fourteen StAR acetylomes undergoing acetylation and deacetylation, K111 and K253 were frequently recognized either endogenously or in response to HDACIs. Site-directed mutagenesis studies of these two StAR acetylomes, pertaining to K111Q and K253Q acetylation mimetic states, resulted in increases in E2 levels in ER+ MCF7 and triple negative MB-231 BC cells, compared with their values seen with human StAR. Conversely, these cells carrying K111R and K253R deacetylation mutants diminished E2 biosynthesis. These findings provide novel and mechanistic insights into intra-tumoral E2 regulation by elucidating the functional importance of this uncovered StAR post-translational modification (PTM), involving acetylation and deacetylation events, underscoring the potential of StAR as a therapeutic target for hormone-sensitive BC. Full article
(This article belongs to the Special Issue Hormonal Diversity: From Organogenesis to Neurodegeneration)
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