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Minerva Endocrinologica Mar 2005Loss of estrogens or androgens causes bone loss by increasing the rate of bone remodeling, and also causes an imbalance between resorption and formation by prolonging... (Review)
Review
Loss of estrogens or androgens causes bone loss by increasing the rate of bone remodeling, and also causes an imbalance between resorption and formation by prolonging the lifespan of osteoclasts and shortening the lifespan of osteoblasts. Conversely, treatment with androgens, as well as estrogens, maintains cancellous bone mass and integrity, regardless of age or sex. Both androgens, via the androgen receptor (AR), and estrogens, via the estrogen receptors (ERs) can exert these effects, but the relative contribution of these 2 pathways remains uncertain. Androgens, like estrogens, stimulate endochondral bone formation at the start of puberty, whereas they induce epiphyseal closure at the end of puberty, thus, they have a biphasic effect. Androgen action on the growth plate is, however, clearly mediated via aromatization into estrogens and interaction with ER alpha. Androgens increase, while estrogens decrease radial growth. This differential effect of the sex steroids may be important because bone strength in males seems to be determined by higher periosteal bone formation and, therefore, greater bone dimensions. Experiments in mice suggest that both the AR and ER alpha pathways are involved in androgen action on radial bone growth. ER beta may mediate growth-limiting effects of estrogens in the female but does not seem to be involved in the regulation of bone size in males. In conclusion, androgens may protect men against osteoporosis via maintenance of cancellous bone mass and expansion of cortical bone. This androgen action on bone is mediated by the AR and ER alpha.
Topics: Androgens; Animals; Bone and Bones; Estrogen Receptor alpha; Female; Humans; Male; Osteoblasts; Osteoporosis; Periosteum; Receptors, Androgen
PubMed: 15877010
DOI: No ID Found -
BMJ Case Reports Jun 2021Adrenocortical carcinoma (ACC) is a rare malignancy, with an estimated annual incidence of 0.7-2 cases per million and a median overall survival of 3-4 years....
Adrenocortical carcinoma (ACC) is a rare malignancy, with an estimated annual incidence of 0.7-2 cases per million and a median overall survival of 3-4 years. Hormone-secreting ACCs represent most cases; of these, only a small minority presents with virilisation alone. Early diagnosis is key to increase the chances of a better outcome. Here, we report a case of a 41-year-old woman who presented with menstrual irregularities, hirsutism and virilising symptoms, associated with abdominal discomfort and constitutional symptoms. On physical examination, there was a palpable mass in the right upper quadrant. Laboratory workup revealed elevated serum androgens. The imaging study showed a 163×110×122 cm right adrenal mass with features consistent with ACC and suggested potential hepatic invasion. Our patient underwent surgical resection, and the histopathological findings confirmed the diagnosis. She was referred to a specialised centre for follow-up and adjuvant therapy.
Topics: Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Adult; Androgens; Female; Humans; Liver; Virilism
PubMed: 34083198
DOI: 10.1136/bcr-2021-242895 -
International Journal of Molecular... Dec 2022Hidradenitis suppurativa (HS) is a chronic inflammatory disease manifesting in inverse body regions. In a systematic review, the role of hormones in HS will be presented... (Review)
Review
Hidradenitis suppurativa (HS) is a chronic inflammatory disease manifesting in inverse body regions. In a systematic review, the role of hormones in HS will be presented to better understand the pathomechanisms of HS. The review is based on the PRISMA criteria. Systematic research was carried out using keywords. Subsequently, the data were analyzed based on the clinical response and other relevant information. The main focus of our systematic review was on HS manifestation, exacerbation, sex hormones, antiandrogen therapy, thyroid function, polycystic ovary syndrome, insulin resistance, and adipokines. In HS, there appears to be a dysregulated adipokine release that is shifted towards pro-inflammatory adipokines. Insulin resistance is significantly more common in HS than in healthy patients regardless of BMI, age, and gender. Insulin resistance in HS patients leads to further cardiovascular disease. The mechanism of insulin resistance and role of adipokines should be investigated in future studies to better provide the pathomechanisms of HS. The role of androgens seems to be important in a certain subgroup of female patients. Anti-androgenic therapy can be useful and helpful in some patients. However, further studies are needed to better understand the hormonal relationship in HS.
Topics: Humans; Female; Insulin Resistance; Hidradenitis Suppurativa; Androgens; Gonadal Steroid Hormones; Androgen Antagonists
PubMed: 36499573
DOI: 10.3390/ijms232315250 -
International Journal of Molecular... Nov 2022Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Despite its incidence, the syndrome is poorly understood and remains... (Review)
Review
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Despite its incidence, the syndrome is poorly understood and remains underdiagnosed, and female patients are diagnosed with a delay. The heterogenous nature of this complex disorder results from the combined occurrence of genetic, environmental, endocrine, and behavioral factors. Primary clinical manifestations of PCOS are derived from the excess of androgens (anovulation, polycystic ovary morphology, lack of or scanty, irregular menstrual periods, acne and hirsutism), whereas the secondary manifestations include multiple metabolic, cardiovascular, and psychological disorders. Dietary and lifestyle factors play important roles in the development and course of PCOS, which suggests strong epigenetic and environmental influences. Many studies have shown a strong association between PCOS and chronic, low-grade inflammation both in the ovarian tissue and throughout the body. In the vast majority of PCOS patients, elevated values of inflammatory markers or their gene markers have been reported. Development of the vicious cycle of the chronic inflammatory state in PCOS is additionally stimulated by hyperinsulinemia and obesity. Changes in DNA methylation, histone acetylation and noncoding RNA levels are presented in this review in the context of oxidative stress, reactive oxygen species, and inflammatory signaling in PCOS. Epigenetic modulation of androgenic activity in response to inflammatory signaling is also discussed.
Topics: Female; Humans; Polycystic Ovary Syndrome; Hirsutism; Anovulation; Androgens; Hyperinsulinism
PubMed: 36498989
DOI: 10.3390/ijms232314663 -
Journal of Comparative Physiology. A,... Jan 2018Singing of songbirds is sensitive to testosterone and its androgenic and estrogenic metabolites in a species-specific way. The hormonal effects on song pattern are... (Review)
Review
Singing of songbirds is sensitive to testosterone and its androgenic and estrogenic metabolites in a species-specific way. The hormonal effects on song pattern are likely mediated by androgen receptors (AR) and estrogen receptor alpha (ERα), ligand activated transcription factors that are expressed in neurons of various areas of the songbirds' vocal control circuit. The distribution of AR in this circuit is rather similar between species while that of ERα is species variant and concerns a key vocal control area, the HVC (proper name). We discuss the regulation of the expression of the cognate AR and ERα and putative splice variants. In particular, we suggest that transcription factor binding sites in the promoter of these receptors differ between bird species. Further, we suggest that AR- and ERα-dependent gene regulation in vocal areas differs between species due to species-specific DNA binding sites of putative target genes that are required for the transcriptional activity of the receptors. We suggest that species differences in the distribution of AR and ERα in vocal areas and in the genomic sensitivity to these receptors contribute to species-specific hormonal regulation of the song.
Topics: Androgens; Animals; Brain; Estrogens; Gene Expression Regulation; Humans; Songbirds; Vocalization, Animal
PubMed: 29209770
DOI: 10.1007/s00359-017-1236-y -
Biology of Sex Differences Jul 2020Sex hormones and their respective receptors affect vascular function differently in men and women, so it is reasonable to assume they play a role in the sex differences... (Review)
Review
Sex hormones and their respective receptors affect vascular function differently in men and women, so it is reasonable to assume they play a role in the sex differences in cardiovascular disease states. This review focuses on how the effects of testosterone on arterial vessels impact the female vasculature. In women with androgen-excess polycystic ovary syndrome, and in transgender men, testosterone exposure is associated with high blood pressure, endothelial dysfunction, and dyslipidemia. These relationships suggest that androgens may exert pathophysiological effects on the female vasculature, and these effects on the female vasculature appear to be independent from other co-morbidities of cardiovascular disease. There is evidence that the engagement of androgens with androgen receptor induces detrimental outcomes in the female cardiovascular system, thereby representing a potential causative link with sex differences and cardiovascular regulation. Gender affirming hormone therapy is the primary medical intervention sought by transgender people to reduce the characteristics of their natal sex and induce those of their desired sex. Transgender men, and women with androgen-excess polycystic ovary syndrome both represent patient groups that experience chronic hyperandrogenism and thus lifelong exposure to significant medical risk. The study of testosterone effects on the female vasculature is relatively new, and a complex picture has begun to emerge. Long-term research in this area is needed for the development of more consistent models and controlled experimental designs that will provide insights into the impact of endogenous androgen concentrations, testosterone doses for hormone therapy, and specific hormone types on function of the female cardiovascular system.
Topics: Androgens; Animals; Female; Humans; Male; Polycystic Ovary Syndrome; Testosterone; Transgender Persons
PubMed: 32727622
DOI: 10.1186/s13293-020-00323-6 -
American Journal of Physiology. Cell... Sep 2022The effects of androgens have been extensively studied in a variety of organs and cell types with an increasing focus on the sexually dimorphic role androgens play not... (Review)
Review
The effects of androgens have been extensively studied in a variety of organs and cell types with an increasing focus on the sexually dimorphic role androgens play not only with respect to cellular functions but also in metabolism. Although the classical mechanism of androgen action is via ligand-dependent binding with the nuclear transcription factor, androgen receptor (AR), cytosolic AR can also activate second messenger signaling pathways. Given that cytosolic AR can signal in this manner, there has been increased interest in the mechanisms by which androgens may control cellular organelle function. This review highlights the effects that androgens have on mitochondrial structure and function with emphasis on biogenesis, fusion/fission, mitophagy, bioenergetics (oxidative phosphorylation), and reactive oxygen species production. There are a number of publications on the effects of androgens in these general areas of mitochondrial function. However, the precise mechanisms by which androgens cause these effects are not known. In addition, given that the nucleus and mitochondria work in tandem to control mitochondrial function and the mitochondria have their own DNA, future research efforts should focus on the direct, mechanistic effects of androgens on mitochondrial function.
Topics: Androgens; Mitochondria; Oxidative Phosphorylation; Receptors, Androgen; Signal Transduction
PubMed: 35704694
DOI: 10.1152/ajpcell.00205.2022 -
Hormone and Metabolic Research =... Dec 2022By the end of December 2019 new corona virus began to spread from Wuhan, China and caused a worldwide pandemic. COVID-19 deaths and prevalence represented sex discrepant... (Review)
Review
By the end of December 2019 new corona virus began to spread from Wuhan, China and caused a worldwide pandemic. COVID-19 deaths and prevalence represented sex discrepant patterns with higher rate of deaths and infection in males than females which could be justified by androgen-mediated mechanisms. This review aimed to assess the role of androgens in COVID-19 severity and mortality. Androgens increase expressions of Type II transmembrane Serine Protease (TMPRSS2) and Angiotensin Converting Enzyme 2 (ACE2), which both facilitate new corona virus entry into host cell and their expression is higher in young males than females. According to observational studies, prevalence of COVID-19 infections and deaths was more in androgenic alopecic patients than patients without androgenic alopecia. The COVID-19 mortality rates in aged men (>60 years) were substantially higher than aged females and even young males caused by high inflammatory activities such as cytokine storm due to hypogonadism in this population. Use of anti-androgen and TMPRSS2 inhibitor drugs considerably modified COVID-19 symptoms. Androgen deprivation therapy also improved COVID-19 symptoms in prostate cancer: overall the role of androgens in severity of COVID-19 and its associated mortality seemed to be very important. So, more studies in variety of populations are required to define the absolute role of androgens.
Topics: Humans; Male; Aged; Androgens; COVID-19; Androgen Antagonists; Prostatic Neoplasms; China
PubMed: 36195265
DOI: 10.1055/a-1954-5605 -
Reproductive Toxicology (Elmsford, N.Y.) Oct 2018A systematic literature review was conducted to identify Hershberger bioassays for ∼3200 chemicals including those used to validate the OECD/US EPA guideline assay, US... (Review)
Review
A systematic literature review was conducted to identify Hershberger bioassays for ∼3200 chemicals including those used to validate the OECD/US EPA guideline assay, US EPA's chemicals screened for endocrine activity, and the library of chemicals run in US EPA 's ToxCast in vitro assays. For 134 chemicals that met pre-defined criteria, experimental results were extracted into a database used to characterize uncertainty in results and evaluate the concordance of the Hershberger assay with other in vivo rodent studies that measure androgen-responsive endpoints. Of 25 chemicals tested in >1 Hershberger study, 28% had disagreements between studies (i.e. ≥1 positive and ≥1 negative study), and of the 65 chemicals tested in Hershberger studies and other in vivo studies with androgen-responsive endpoints, 43% indicated disagreements, though in some cases these may be explained by differences in study designs or physiology of the animal model. Ultimately, 49 chemicals were identified with reproducible androgen pathway responses confirmed in ≥2 in vivo rodent studies that could be considered reference chemicals useful for validating alternative methods.
Topics: Androgen Antagonists; Androgens; Animals; Biological Assay; Humans
PubMed: 30205136
DOI: 10.1016/j.reprotox.2018.08.016 -
Hormones and Behavior May 2008Reduced androgen levels in aged men and women might be risk factors for age-related cognitive decline and Alzheimer's disease (AD). Ongoing clinical trials are designed... (Review)
Review
Reduced androgen levels in aged men and women might be risk factors for age-related cognitive decline and Alzheimer's disease (AD). Ongoing clinical trials are designed to evaluate the potential benefit of estrogen in women and of testosterone in men. In this review, we discuss the potential beneficial effects of androgens and androgen receptors (ARs) in males and females. In addition, we discuss the hypothesis that AR interacts with apolipoprotein (apoE)4, encoded by epsilon4 and a risk factor for age-related cognitive decline and AD, and the potential consequences of this interaction.
Topics: Aged; Aging; Alzheimer Disease; Androgens; Apolipoproteins E; Cognition; Cognition Disorders; Female; Humans; Male; Receptors, Androgen; Risk Factors; Sex Characteristics; Testosterone
PubMed: 18395206
DOI: 10.1016/j.yhbeh.2008.02.012