Elevated Levels of Estrogen Suppress Hepcidin Synthesis and Enhance Serum Iron Availability in Premenopausal Women

Bajbouj, Khuloud; Shafarin, Jasmin; Allam, Hilda; Madkour, Mohamed; Awadallah, Samir; Elserafy, Ahmed Shawky; Sandeep, Divyasree; Hamad, Mawieh

doi:10.1055/s-0043-124077

Cited by 25 publications

(20 citation statements)

References 36 publications

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“…These findings are in line with a study demonstrating a significant reduction in serum hepcidin without correlation with serum iron in female patients with elevated estrogens, due to fertility treatments [157]. On the other hand, in a study with premenopausal women during various phases of their monthly cycle, serum 17β-estradiol was negatively correlated with hepcidin and positively correlated with iron [158]. Definitely, more work is required to clarify the mechanism and physiological relevance of hepcidin regulation by estrogens before considering any therapeutic applications.…”

Section: Inhibitors Of Hepcidin Expressionsupporting

confidence: 88%

Hepcidin Therapeutics

Κατσαρού

Pantopoulos

2018

Pharmaceuticals

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Hepcidin is a key hormonal regulator of systemic iron homeostasis and its expression is induced by iron or inflammatory stimuli. Genetic defects in iron signaling to hepcidin lead to “hepcidinopathies” ranging from hereditary hemochromatosis to iron-refractory iron deficiency anemia, which are disorders caused by hepcidin deficiency or excess, respectively. Moreover, dysregulation of hepcidin is a pathogenic cofactor in iron-loading anemias with ineffective erythropoiesis and in anemia of inflammation. Experiments with preclinical animal models provided evidence that restoration of appropriate hepcidin levels can be used for the treatment of these conditions. This fueled the rapidly growing field of hepcidin therapeutics. Several hepcidin agonists and antagonists, as well as inducers and inhibitors of hepcidin expression have been identified to date. Some of them were further developed and are currently being evaluated in clinical trials. This review summarizes the state of the art.

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Section: Inhibitors Of Hepcidin Expressionsupporting

confidence: 88%

Hepcidin Therapeutics

Κατσαρού

Pantopoulos

2018

Pharmaceuticals

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“…Before the onset of menopause hepcidin levels in women are nearly 50% lower than in males of corresponding ages. After the menopause, hepcidin levels tend to be similar in both sexes [212,213] or slightly increased in men [214]. These results demonstrate a negative correlation between ferritin and estrogen levels during the menopausal transition period [215].…”

Section: Iron and Strokementioning

confidence: 58%

Age-Related Changes and Sex-Related Differences in Brain Iron Metabolism

Kezele

Ćurko-Cofek

2020

Nutrients

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Iron is an essential element that participates in numerous cellular processes. Any disruption of iron homeostasis leads to either iron deficiency or iron overload, which can be detrimental for humans’ health, especially in elderly. Each of these changes contributes to the faster development of many neurological disorders or stimulates progression of already present diseases. Age-related cellular and molecular alterations in iron metabolism can also lead to iron dyshomeostasis and deposition. Iron deposits can contribute to the development of inflammation, abnormal protein aggregation, and degeneration in the central nervous system (CNS), leading to the progressive decline in cognitive processes, contributing to pathophysiology of stroke and dysfunctions of body metabolism. Besides, since iron plays an important role in both neuroprotection and neurodegeneration, dietary iron homeostasis should be considered with caution. Recently, there has been increased interest in sex-related differences in iron metabolism and iron homeostasis. These differences have not yet been fully elucidated. In this review we will discuss the latest discoveries in iron metabolism, age-related changes, along with the sex differences in iron content in serum and brain, within the healthy aging population and in neurological disorders such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and stroke.

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“…Lastly, the organic pollutant polychlorinated biphenyls (PCBs) inhibits HAMP expression through an E2-like effect that associates with disrupted iron homeostasis [22]. In humans, several reports have suggested that elevated levels of serum E2 correlate positively with serum iron status [18][19][20][21][22] and negatively with serum HAMP concertation [23,24]. Mean serum iron levels significantly increase in women on contraceptives [25][26][27][28].…”

Section: E2 and Iron Metabolismmentioning

confidence: 99%

The Case for an Estrogen-iron Axis in Health and Disease

Hamad

Bajbouj

Taneera

2019

Exp Clin Endocrinol Diabetes

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Clinical and experimental evidence suggest that estrogen manipulates intracellular iron metabolism and that elevated levels of estrogen associate with increased systemic iron availability. This has been attributed to the ability of estrogen to suppress hepcidin synthesis, maintain ferroportin integrity and enhance iron release from iron-absorbing duodenal enterocytes and iron-storing macrophages and hepatocytes. These observations speak of a potential “estrogen-iron” axis that manipulates iron metabolism in response to hematologic (erythropoiesis) and non-hematologic (uterine growth, pregnancy, lactation) needs for iron. Such an axis could contribute to minimizing iron deficiency in premenopausal women and iron overload in postmenopausal women. It could also exacerbate iron overload and related clinical consequences including cancer, osteoporosis, cardiovascular complications and neurodegenerative symptoms, especially in postmenopausal women on hormonal replacement therapy. Understanding the role of estrogen in iron metabolism may shed some light on the pleotropic, but often paradoxical, roles of estrogen in human health and disease.

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Elevated Levels of Estrogen Suppress Hepcidin Synthesis and Enhance Serum Iron Availability in Premenopausal Women

Cited by 25 publications

References 36 publications

Hepcidin Therapeutics

Hepcidin Therapeutics

Age-Related Changes and Sex-Related Differences in Brain Iron Metabolism

The Case for an Estrogen-iron Axis in Health and Disease

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