There is no turning back on the paradigm shift on the actions of human chorionic gonadotropin and luteinizing hormone

Rao, Ch.V.

doi:10.1016/j.jrhm.2015.07.001

Cited by 6 publications

(8 citation statements)

References 105 publications

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“…The paradigm shift has changed this dogma. 27 It has revealed that functional LH/hCG receptors are also present in central and peripheral (spinal cord and adrenal pheochromocytoma cells, which have an embryological origin with neural crest) nervous systems among the other nongonadal tissues. [28][29][30] The LH/hCG receptors have been demonstrated in fetal rat brain and in adult rat, mouse, bovine, and human brains.…”

Section: Amyloid Plaques and Neurofibrillary Tanglesmentioning

confidence: 99%

Involvement of Luteinizing Hormone in Alzheimer Disease Development in Elderly Women

Rao

2017

Reprod. Sci.

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Alzheimer disease (AD) is a slow progressive neurodegenerative disease that affects more elderly women than elderly men. It impairs memory, typically progresses into multidomain cognitive decline that destroys the quality of life, and ultimately leads to death. About 5.3 million older Americans are now living with this disease, and this number is projected to rise to 14 million by 2050. Annual health-care costs in the United States alone are projected to increase to about US$1.1 trillion by 2050. The initial theory that decreasing estrogen levels leads to AD development in postmenopausal women has been proven inconclusive. For example, Women's Health Research Initiative Memory Study and the population-based nested case-control study have failed to demonstrate that estrogen/progesterone (hormone replacement therapy [HRT]) or estrogen replacement therapy could prevent the cognitive decline or reduce the risk of AD. This led to the realization that AD development could be due to a progressive increase in luteinizing hormone (LH) levels in postmenopausal women. Accordingly, a large number of studies have demonstrated that an increase in LH levels is positively correlated with neuropathological, behavioral, and cognitive changes in AD. In addition, LH has been shown to promote amyloidogenic pathway of precursor protein metabolism and deposition of amyloid β plaques in the hippocampus, a region involved in AD. Cognate receptors that mediate LH effects are abundantly expressed in the hippocampus. Reducing the LH levels by treatment with gonadotropin-releasing hormone agonists could provide therapeutic benefits. Despite these advances, many questions remain and require further research.

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Section: Amyloid Plaques and Neurofibrillary Tanglesmentioning

confidence: 99%

Involvement of Luteinizing Hormone in Alzheimer Disease Development in Elderly Women

Rao

2017

Reprod. Sci.

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“…As the name implied, investigators have believed for a long time that hCG and LH are only capable of regulating gonadal secretion of steroid hormones. 95 The secreted steroid hormones will then regulate the other tissues. This paradigm has begun to shift as more and more investigators have found the presence of hCG/LH receptors in many nongonadal tissues in the body.…”

Section: Paradigm Shift On the Hcg/lh Actionsmentioning

confidence: 99%

Protective Effects of Human Chorionic Gonadotropin Against Breast Cancer: How Can We Use This Information to Prevent/Treat the Disease?

Rao

2017

Reprod. Sci.

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Breast cancers (BCs) are the most common malignancies among women worldwide. Giving birth to a first child before 24 years of age decreases the BC risk by about half, when women reach menopausal years. The scientific evidence suggests that the actions of human chorionic gonadotropin (hCG) are responsible for this decrease. Human BC cells and tissues contain hCG/luteinizing hormone receptors. The activation of the receptors results in an increase in cell differentiation and apoptosis. Conversely, it decreases the cell proliferation, invasion, and survival. The hCG actions are primarily cyclic adenosine monophosphate/protein kinase A mediated, require the presence of receptors, and involve blocking the activation and nuclear translocation of the transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). The women with a higher hCG levels during pregnancy tend to have a lower BC incidence and those with the receptor-positive tumors have a longer metastasis-free survival. The long-term benefits of pregnancy/hCG seem to come from permanent signature genomic imprinting and expression changes, which are characterized by low cell proliferation, increased efficiency of DNA repair mechanisms, cell differentiation, and cells resistance to carcinogenesis. These findings could provide clinical opportunities to use hCG for the prevention of BC in this modern era of increasing number of young women in our societies waiting longer than ever to have their first child. In addition, hCG may be useful to reduce and/or eliminate cellular targets of carcinogenic changes during an active ongoing disease.

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“…10,11 Instead of showing all the tissues that hCG can regulate, which can be found in the references listed in Table 1, only the relevant tissues to the therapeutic indications are shown.…”

Section: 10mentioning

confidence: 99%

Inclusion of Human Chorionic Gonadotropin in the Family of Therapeutic Glycoproteins

Rao¹

2017

Women Health Open J

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The family of therapeutic glycoproteins contains many members. Some of them have become valuable therapeutic agents in saving the countless number of human lives from some of the most dreadful diseases. They are increasingly taking a center stage among biotherapeutics. The technologies of glycoengineering are making a further impact by modifying the glycan moieties, which make them biologically more active and increase their effectiveness and pharmacokinetics, etc. Human Chorionic Gonadotropin (hCG) has been used in reproductive medicine for the last several decades. The paradigm shift on the hCG actions has created additional therapeutic opportunities against many menacing and dangerous diseases that are no less important than the ones treated by some of the prominent members of the therapeutic glycoproteins family. However, to the best of the authors' knowledge, hCG has never been included in this family or tapped the potential of glycoengineering to make hCG even more therapeutically effective than the currently used preparations. It is time to include hCG in the family and begin glycoengineering on recombinant hormone.

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There is no turning back on the paradigm shift on the actions of human chorionic gonadotropin and luteinizing hormone

Cited by 6 publications

References 105 publications

Involvement of Luteinizing Hormone in Alzheimer Disease Development in Elderly Women

Involvement of Luteinizing Hormone in Alzheimer Disease Development in Elderly Women

Protective Effects of Human Chorionic Gonadotropin Against Breast Cancer: How Can We Use This Information to Prevent/Treat the Disease?

Inclusion of Human Chorionic Gonadotropin in the Family of Therapeutic Glycoproteins

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