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Journal of Neuro-oncology Jan 2023Meningiomas are associated with several gonadal steroid hormone-related risk factors and demonstrate a predominance in females. These associations led to investigations... (Review)
Review
INTRODUCTION
Meningiomas are associated with several gonadal steroid hormone-related risk factors and demonstrate a predominance in females. These associations led to investigations of the role that hormones may have on meningioma growth and development. While it is now accepted that most meningiomas express progesterone and somatostatin receptors, the conclusion for other receptors has been less definitive.
METHODS
We performed a review of what is known regarding the relationship between hormones and meningiomas in the published literature. Furthermore, we reviewed clinical trials related to hormonal agents in meningiomas using MEDLINE PubMed, Scopus, and the NIH clinical trials database.
RESULTS
We identify that all steroid-hormone trials lacked receptor identification or positive receptor status in the majority of patients. In contrast, four out of five studies involving somatostatin analogs used positive receptor status as part of the inclusion criteria.
CONCLUSIONS
Several clinical trials have recently been completed or are now underway using somatostatin analogs in combination with other therapies that appear promising, but a reevaluation of hormone-based monotherapy is warranted. Synthesizing this evidence, we clarify the remaining questions and present future directions for the study of the biological role and therapeutic potential of hormones in meningioma and discuss how the stratification of patients using features such as grade, receptor status, and somatic mutations, might be used for future trials to select patients most likely to benefit from specific therapies.
Topics: Female; Humans; Meningioma; Meningeal Neoplasms; Receptors, Progesterone; Receptors, Estrogen; Progesterone; Somatostatin
PubMed: 36418843
DOI: 10.1007/s11060-022-04187-1 -
Gerontology 2015Significant advances in health and social wellbeing have led to linear gains in life expectancy and an accompanying increase in the burden imposed by age-related... (Review)
Review
Significant advances in health and social wellbeing have led to linear gains in life expectancy and an accompanying increase in the burden imposed by age-related morbidities. Complex alterations in hormonal networks which regulate homeostasis and survival may underlie this poor adaptation to later life, as exemplified by an increased fracture risk amongst post-menopausal women. Beyond overt under- or overactivity of hormonal axes, changes in the concentrations of regulatory hormones may also impact on health and disease. Subclinical hyperthyroidism, a disorder characterised by normal thyroxine levels in the presence of decreased thyroid-stimulating hormone, is, for instance, independently associated with an increased risk of atrial fibrillation amongst elderly populations. Both the menopause and subclinical thyroid disease demonstrate the difficulty in reversing endocrine changes in later life, with minimal impact from thyroxine therapy in subclinical hypothyroidism and multiple reports of harm resulting from hormone replacement therapy in peri- and post-menopausal women. Given these findings, strategies to locally regulate hormone bioavailability by altering pre-receptor metabolism may offer greater therapeutic potential in the fight against age-related disease. This review aims to provide an overview of the ageing endocrine system and its potential impact on health and disease in the elderly. It will postulate that strategies to coordinate pre-receptor hormone metabolism and a greater understanding of putative hormonal longevity pathways may offer key new drug targets in the fight against ageing, and will argue against applying the conventional endocrine maxim of 'block and replace' to hormonal changes seen during ageing.
Topics: Aging; Endocrine System; Female; Hormones; Humans; Male
PubMed: 25471682
DOI: 10.1159/000367692 -
Molecular and Cellular Endocrinology Jun 2021As the most frequent women's cancer, breast cancer causes the second most cancer-related death in women worldwide. Majority of the breast cancers are hormone... (Review)
Review
As the most frequent women's cancer, breast cancer causes the second most cancer-related death in women worldwide. Majority of the breast cancers are hormone receptor-positive and commonly treated by hormone therapy. Thus, the expression levels of hormone receptors signaling pathways are pivotal in the development and therapy of breast cancer. The expression of hormone receptors signaling pathways is not only regulated at the transcription level but also at the post-transcription level by both proteins and RNAs. In addition to that, the function of hormone receptors can also be regulated by RNAs. In this review, we summarize the roles of RNAs in hormone receptor-positive breast cancer. We introduce how mRNA stability and protein function of genes in hormone receptors signaling pathways are regulated by RNA-binding proteins, miRNAs, and lncRNAs. We believe these proteins and RNAs can be potential therapeutic targets of breast cancer.
Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Estrogens; Female; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; MCF-7 Cells; MicroRNAs; Neoplasm Proteins; Progesterone; RNA, Long Noncoding; RNA, Messenger; Receptors, Cell Surface; Signal Transduction; Testosterone
PubMed: 33711334
DOI: 10.1016/j.mce.2021.111221 -
Indian Journal of Dermatology,... 2013Underlying hormone imbalances may render acne unresponsive to conventional therapy. Relevant investigations followed by initiation of hormonal therapy in combination... (Review)
Review
Underlying hormone imbalances may render acne unresponsive to conventional therapy. Relevant investigations followed by initiation of hormonal therapy in combination with regular anti-acne therapy may be necessary if signs of hyperandrogenism are present. In addition to other factors, androgen-stimulated sebum production plays an important role in the pathophysiology of acne in women. Sebum production is also regulated by other hormones, including estrogens, growth hormone, insulin, insulin-like growth factor-1, glucocorticoids, adrenocorticotropic hormone, and melanocortins. Hormonal therapy may also be beneficial in female acne patients with normal serum androgen levels. An understanding of the sebaceous gland and the hormonal influences in the pathogenesis of acne would be essential for optimizing hormonal therapy. Sebocytes form the sebaceous gland. Human sebocytes express a multitude of receptors, including receptors for peptide hormones, neurotransmitters and the receptors for steroid and thyroid hormones. Various hormones and mediators acting through the sebocyte receptors play a role in the orchestration of pathogenetic lesions of acne. Thus, the goal of hormonal treatment is a reduction in sebum production. This review shall focus on hormonal influences in the elicitation of acne via the sebocyte receptors, pathways of cutaneous androgen metabolism, various clinical scenarios and syndromes associated with acne, and the available therapeutic armamentarium of hormones and drugs having hormone-like actions in the treatment of acne.
Topics: Acne Vulgaris; Hormones; Humans; Hyperandrogenism; Hypoglycemic Agents; Metformin; Sebaceous Glands
PubMed: 23619437
DOI: 10.4103/0378-6323.110765 -
Molecular Human Reproduction May 2023Currently, our understanding of hormonal regulation within the female reproductive system is largely based on our knowledge of estrogen and progesterone signalling.... (Review)
Review
Currently, our understanding of hormonal regulation within the female reproductive system is largely based on our knowledge of estrogen and progesterone signalling. However, while the important functions of androgens in male physiology are well known, it is also recognized that androgens play critical roles in the female reproductive system. Further, androgen signalling is altered in a variety of gynaecological conditions, including endometriosis and polycystic ovary syndrome, indicative of regulatory roles in endometrial and ovarian function. Co-regulatory mechanisms exist between different androgens, estrogens, and progesterone, resulting in a complex network of steroid hormone interactions. Evidence from animal knockout studies, in vitro experiments, and human data indicate that androgen receptor expression is cell-specific and menstrual cycle stage-dependent, with important regulatory roles in the menstrual cycle, endometrial biology, and follicular development in the ovaries. This review will discuss the expression and co-regulatory interactions of androgen receptors, highlighting the complexity of the androgen signalling pathway in the endometrium and ovaries, and the synthesis of androgens from additional alternative pathways previously disregarded as male-specific. Moreover, it will illustrate the challenges faced when studying androgens in female biology, and the need for a more in-depth, integrative view of androgen metabolism and signalling in the female reproductive system.
Topics: Animals; Male; Female; Humans; Androgens; Ovary; Progesterone; Endometrium; Estrogens; Receptors, Androgen
PubMed: 37171897
DOI: 10.1093/molehr/gaad017 -
Journal of Internal Medicine Dec 2018Obesity and its comorbidities, such as type 2 diabetes, are pressing worldwide health concerns. Available anti-obesity treatments include weight loss pharmacotherapies... (Review)
Review
Obesity and its comorbidities, such as type 2 diabetes, are pressing worldwide health concerns. Available anti-obesity treatments include weight loss pharmacotherapies and bariatric surgery. Whilst surgical interventions typically result in significant and sustained weight loss, available pharmacotherapies are far less effective, typically decreasing body weight by no more than 5-10%. An emerging class of multi-agonist drugs may eventually bridge this gap. This new class of specially tailored drugs hybridizes the amino acid sequences of key metabolic hormones into one single entity with enhanced potency and sustained action. Successful examples of this strategy include multi-agonist drugs targeting the receptors for glucagon-like peptide-1 (GLP-1), glucagon and the glucose-dependent insulinotropic polypeptide (GIP). Due to the simultaneous activity at several metabolically relevant receptors, these multi-agonists offer improved body weight loss and glucose tolerance relative to their constituent monotherapies. Further advancing this concept, chimeras were generated that covalently link nuclear acting hormones such as oestrogen, thyroid hormone (T ) or dexamethasone to peptide hormones such as GLP-1 or glucagon. The benefit of this strategy is to restrict the nuclear hormone action exclusively to cells expressing the peptide hormone receptor, thereby maximizing combinatorial metabolic efficacy of both drug constituents in the target cells whilst preventing the nuclear hormone cargo from entering and acting on cells devoid of the peptide hormone receptor, in which the nuclear hormone might have unwanted effects. Many of these multi-agonists are in preclinical and clinical development and may represent new and effective tools in the fight against obesity and its comorbidities.
Topics: Animals; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Humans; Obesity; Peptides
PubMed: 30230640
DOI: 10.1111/joim.12837 -
Oncology Reports Oct 2021Ovarian cancer (OC) remains the leading cause of mortality due to gynecological malignancies. Epidemiological studies have demonstrated that steroid hormones released... (Review)
Review
Ovarian cancer (OC) remains the leading cause of mortality due to gynecological malignancies. Epidemiological studies have demonstrated that steroid hormones released from the hypothalamic‑pituitary‑ovarian axis can play a role in stimulating or inhibiting OC progression, with gonadotropins, estrogens and androgens promoting OC progression, while gonadotropin‑releasing hormone (GnRH) and progesterone may be protective factors in OC. Experimental studies have indicated that hormone receptors are expressed in OC cells and mediate the growth stimulatory or growth inhibitory effects of hormones on these cells. Hormone therapy agents have been evaluated in a number of clinical trials. The majority of these trials were conducted in patients with relapsed or refractory OC with average efficacy and limited side‑effects. A better understanding of the mechanisms through which hormones affect cell growth may improve the efficacy of hormone therapy. In the present review article, the role of hormones (GnRH, gonadotropins, androgens, estrogens and progestins) and their receptors in OC tumorigenesis, and hormonal therapy in OC treatment is discussed and summarized.
Topics: Androgens; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Ovarian Neoplasms; Progestins
PubMed: 34435651
DOI: 10.3892/or.2021.8174 -
Acta Oncologica (Stockholm, Sweden) Apr 2024Tamoxifen remains an important adjuvant treatment in premenopausal patients with hormone receptor-positive breast cancer. Thus, determination of hormone receptors is... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND PURPOSE
Tamoxifen remains an important adjuvant treatment in premenopausal patients with hormone receptor-positive breast cancer. Thus, determination of hormone receptors is important. Here, we compare cytosol-based methods, immunohistochemistry (IHC), and gene expression (GEX) analysis for determining hormone receptor status in premenopausal breast cancer patients from a randomised tamoxifen trial, to evaluate their performance in identifying patients that benefit from tamoxifen.
PATIENTS AND METHODS
Premenopausal patients (n=564) were randomised to 2 years of tamoxifen or no systemic treatment. Estrogen receptor (ER) and progesterone receptor (PR) status by protein expression measured by cytosol-based methods and IHC, and mRNA by GEX analysis were compared in 313 patients with available data from all methods. Kaplan Meier estimates and Cox regression were used to evaluate the treatment-predictive value for recurrence-free interval (RFi) and overall survival (OS). Median follow-up for event-free patients was 26 (RFi) and 33 (OS) years.
RESULTS
The mRNA data of ESR1 and PGR distributed bimodally, patterns confirmed in an independent cohort. Kappa-values between all methods were 0.76 and 0.79 for ER and PR, respectively. Tamoxifen improved RFi in patients with ER-positive (ER+) or PR-positive (PR+) tumours (Hazard Ratio [HR] and 95% confidence interval [CI]), cytosol-ER+ 0.53 [0.36-0.79]; IHC-ER+ 0.55 [0.38-0.79]; GEX-ER+ 0.54 [0.37-0.77]; cytosol-PR+ 0.49 [0.34-0.72]; IHC-PR+ 0.58 [0.40-0.85]; GEX-PR+ 0.55 [0.38-0.80]). Results were similar for OS.
INTERPRETATION
These methods can all identify patients that benefit from 2 years of tamoxifen with equal performance, indicating that GEX data might be used to guide adjuvant tamoxifen therapy.
Topics: Humans; Female; Tamoxifen; Antineoplastic Agents, Hormonal; RNA, Messenger; Chemotherapy, Adjuvant; Breast Neoplasms; Receptors, Estrogen; Hormones; Receptors, Progesterone; Treatment Outcome
PubMed: 38587062
DOI: 10.2340/1651-226X.2024.19655 -
Journal of Physiology and Pharmacology... Dec 2014Urocortins (Ucn) 1, 2 and 3 are a group of endogenous peptide hormones belonging to the corticotropin-releasing hormone (CRH) family of peptides. The presence of... (Review)
Review
Urocortins (Ucn) 1, 2 and 3 are a group of endogenous peptide hormones belonging to the corticotropin-releasing hormone (CRH) family of peptides. The presence of urocortins has been detected in the central nervous system as well as in peripheral tissues. They play an important role in a stress response (with respect to its duration, intensity and restoration of homeostasis). They also act as regulatory factors of the cardiovascular, gastrointestinal, reproductive and immune systems. Urocortins act by binding to G-protein-coupled receptors (GPCR). The "central" effects of urocortins are mediated mainly by activation of CRH receptor 1 (CRH-R1), and the "peripheral" effects by activation of CRH-R2. Ucn2 and Ucn3 are selective CRH-R2 agonists and have much higher binding affinity to this receptor than CRH and Ucn1. Recent studies have shown that urocortins exert various biological effects in the cardiovascular system, such as vasodilation, positive inotropic and lusitropic effects, as well as cardioprotection against ischemia-reperfusion injury. They also suppress the renin-angiotensin system and may have an impact on the sympathetic nervous system. Urocortins and CRH-R2 may be a potential therapeutic target in coronary heart disease, congestive heart failure and hypertension. This review summarizes the data published to date on the role of urocortins in the cardiovascular system.
Topics: Animals; Cardiovascular Diseases; Cardiovascular System; Corticotropin-Releasing Hormone; Hemodynamics; Humans; Receptors, Corticotropin-Releasing Hormone; Urocortins
PubMed: 25554979
DOI: No ID Found -
Asian Journal of Andrology 2016Male factor contributes to 50%-60% of overall infertility but is solely responsible in only 20% of couples. Although most male factor infertility is ascertained from an... (Review)
Review
Male factor contributes to 50%-60% of overall infertility but is solely responsible in only 20% of couples. Although most male factor infertility is ascertained from an abnormal semen analysis, other male factors can be contributory especially if the sample returns normal. Male infertility can be due to identifiable hormonal or anatomical etiologies that may be reversible or irreversible. This manuscript will highlight existing guidelines and our recommendations for hormone evaluation for male infertility and empiric therapies including multivitamins, estrogen receptor modulators (clomiphene), estrogen conversion blockers (anastrozole), and hormone replacement.
Topics: Androgens; Antioxidants; Aromatase Inhibitors; Chorionic Gonadotropin; Clomiphene; Estrogens; Follicle Stimulating Hormone; Humans; Infertility, Male; Male; Obesity; Reproductive Control Agents; Selective Estrogen Receptor Modulators; Sex Hormone-Binding Globulin; Testosterone; Vitamins
PubMed: 27098657
DOI: 10.4103/1008-682X.179252