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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 -
Current Opinion in Urology Nov 2010Condoms and vasectomy are male-controlled family planning methods but suffer from limitations in compliance (condoms) and limited reversibility (vasectomy); thus many... (Review)
Review
PURPOSE OF REVIEW
Condoms and vasectomy are male-controlled family planning methods but suffer from limitations in compliance (condoms) and limited reversibility (vasectomy); thus many couples desire other options. Hormonal male contraceptive methods have undergone extensive clinical trials in healthy men and shown to be efficacious, reversible and appear to be well tolerated.
RECENT FINDINGS
The success rate of male hormonal contraception using injectable testosterone alone is high and comparable to methods for women. Addition of progestins to androgens improved the rate of suppression of spermatogenesis. Supported by government or nongovernment organizations, current studies aim to find the best combination of testosterone and progestins for effective spermatogenesis suppression and to explore other delivery methods for these hormones. Translation of these advances to widespread use in the developed world will need the manufacturing and marketing skills of the pharmaceutical industry. Availability of male contraceptives to the developing world may require commitments of governmental and nongovernmental agencies. In a time when imbalance of basic resources and population needs are obvious, this may prove to be a very wise investment.
SUMMARY
Male hormonal contraception is efficacious, reversible and well tolerated for the target population of younger men in stable relationships. Suppression of spermatogenesis is achieved with a combination of an androgen and a progestin. Partnership with industry will accelerate the marketing of a male hormonal contraceptive. Research is ongoing on selective androgen and progesterone receptor modulators that suppress spermatogenesis, minimize potential adverse events while retaining the androgenic and gonadotropin suppressive actions.
Topics: Androgens; Contraception; Contraceptive Agents, Male; Humans; Male; Patient Participation; Spermatogenesis; Treatment Outcome
PubMed: 20808223
DOI: 10.1097/MOU.0b013e32833f1b4a -
The Aging Male : the Official Journal... Sep 2007Problems in the measurement of androgens and in interpreting results have been reviewed and classified as follows: PREANALYTICAL FACTORS: The exact sampling conditions... (Review)
Review
UNLABELLED
Problems in the measurement of androgens and in interpreting results have been reviewed and classified as follows: PREANALYTICAL FACTORS: The exact sampling conditions in relation to circadian and seasonal variations, diet, alcohol, physical activity and posture.
PHYSIOLOGICAL AND MEDICAL FACTORS
Androgen levels vary according to the patient's general health, stress, sexual activity and smoking habits. Analytical variables. Sample preservation and storage variables are often unknown. The different androgen assays used have widely differing accuracy and precision and are subject to large inter-laboratory variation, which especially in women and children can render the results of routinely available direct immunoassays meaningless.
INTERPRETATION OF RESULTS
Laboratory reference ranges vary widely, largely independent of methodology, and fail to take into account the log-normal distribution of androgen values, causing errors in clinical diagnosis and treatment. Other unknowns are antagonists such as SHBG, estrogens, catecholamines, cortisol, and anti-androgens. As well as age, androgen receptor polymorphisms play a major role in regulating androgen levels and resistance to their action.
CONCLUSIONS
Though laboratory assays can support a diagnosis of androgen deficiency in men, they should not be used to exclude it. It is suggested that there needs to be greater reliance on the history and clinical features, together with careful evaluation of the symptomatology, and where necessary a therapeutic trial of androgen treatment given.
Topics: Adult; Aged; Androgens; Diagnostic Tests, Routine; Ethnicity; Health Behavior; Humans; Immunoassay; Male; Middle Aged; United Kingdom
PubMed: 17701661
DOI: 10.1080/13685530701483738 -
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 -
Fertility and Sterility Apr 2002To describe the changes in ovarian hormones caused by natural menopause and hormone replacement therapy that have effects on androgen bioavailability and to describe... (Review)
Review
OBJECTIVE
To describe the changes in ovarian hormones caused by natural menopause and hormone replacement therapy that have effects on androgen bioavailability and to describe indications for androgen replacement in postmenopausal women.
DESIGN
Review of English language-published research over the last 35 years from January 1, 1966 to June 30, 2001 using MEDLINE.
SETTING
Academic medical center.
INTERVENTION(S)
None.
RESULT(S)
In menopausal women, the effects of estradiol depletion and replacement on sex hormone-binding globulin appear to have clinically significant effects on bioavailable endogenous androgens. Many women whose menopause-related symptoms and bone loss responded inadequately to estrogen replacement were found to benefit from the addition of androgens. Most studies have focused on the sexual benefits of prescribing androgens to postmenopausal women. New studies have begun exploring the effects of androgens in other body systems, including the brain and the cardiovascular system.
CONCLUSION(S)
Estrogen depletion and replacement therapy at menopause can have clinically significant effects on bioavailability of endogenous androgens. Androgens complement the actions of estrogens in symptom control and disease prevention in postmenopausal women. Although androgen effects on sexual function are important, effects of androgens in many body systems should be considered in future research to determine optimal postmenopausal hormone replacement therapy.
Topics: Androgens; Estrogens; Female; Hormone Replacement Therapy; Humans; Middle Aged; Osteoporosis; Postmenopause; Sex Hormone-Binding Globulin; Sexuality
PubMed: 12007905
DOI: 10.1016/s0015-0282(02)02967-9 -
Steroids Nov 2023Androgens are a class of steroid hormones primarily associated with male sexual development and physiology, but exert pleiotropic effects in either sex. They have a... (Review)
Review
Androgens are a class of steroid hormones primarily associated with male sexual development and physiology, but exert pleiotropic effects in either sex. They have a crucial role in various physiological processes, including the regulation of skeletal muscle and adipose tissue homeostasis. The effects of androgens are mainly mediated through the androgen receptor (AR), a ligand-activated nuclear receptor expressed in both tissues. In skeletal muscle, androgens via AR exert a multitude of effects, ranging from increased muscle mass and strength, to the regulation of muscle fiber type composition, contraction and metabolic functions. In adipose tissue, androgens influence several processes including proliferation, fat distribution, and metabolism but they display depot-specific and organism-specific effects which differ in certain context. This review further explores the potential mechanisms underlying androgen-AR signaling in skeletal muscle and adipose tissue. Understanding the roles of androgens and their receptor in skeletal muscle and adipose tissue is essential for elucidating their contributions to physiological processes, disease conditions, and potential therapeutic interventions.
Topics: Male; Humans; Androgens; Receptors, Androgen; Adipose Tissue; Muscle, Skeletal; Signal Transduction
PubMed: 37634653
DOI: 10.1016/j.steroids.2023.109306 -
Fertility and Sterility Apr 2002Bone health and strength are dependent on the coupling of cone resorption and bone formation. This process is governed by the interaction of osteoclasts and osteoblasts... (Review)
Review
Bone health and strength are dependent on the coupling of cone resorption and bone formation. This process is governed by the interaction of osteoclasts and osteoblasts plus the modulating influence of the bone mechanicosensory cells-the osteocytes. Both sex steroids-estrogen (E) and testosterone (T)- have receptors on all bone cells, with androgen dominance on osteoblasts and osteocytes. Specific receptors for the weaker androgens, such as DHEA have also been identified. The activity of the sex steroids, influenced by various enzymes found in bone, is reflective of the hormone ligand before its binding to the bone cells. As a result, T acts both directly and via its aromatization to estradiol. The activity of the androgens also varies with the bone surface; periosteal cells, for example, do not have 5alpha-reductase activity, indicating that T is the active metabolite at this clinically important site. Androgens influence bone cell function via local and systemic growth factors and cytokines. By enhancing osteoblast differentiation, androgens regulate bone matrix production, organization, and mineralization. Androgens also regulate osteoclast recruitment and activity. Endogenous androgens increase bone mineral density (BMD) in both adolescent and adult premenopausal women. Women with excess endogenous androgen-for example, those with hirsutism and polycystic ovary syndrome (PCOS)-have increased BMD compared with normal young women. E and androgen therapy increases BMD to a greater degree than does E therapy alone. This is true for both oral combinations of esterified E and methyltestosterone and for subcutaneous T implants. Androgenic progestins have an additive effect on BMD when combined with E therapy and have the further advantage of being protective to the endometrium in E-treated women. Androgens increase muscle mass and strength. The resulting improvement in physical activity leads to the activation of bone-forming sites and the stimulation of the bone formation-modulating cells, the osteocytes. Mechanical loading, when combined with hormone therapy, results in greater osteogenic response than does either alone.
Topics: Androgens; Animals; Bone Density; Bone Remodeling; Bone and Bones; Estrogens; Female; Humans; Muscles; Osteoblasts; Osteoclasts; Receptors, Androgen; Receptors, Estrogen
PubMed: 12007900
DOI: 10.1016/s0015-0282(02)02968-0 -
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 -
Medicine and Science in Sports and... May 2012Historically, the circulation was thought to be the primary source of androgens influencing skeletal muscle. However, a growing body of research indicates that skeletal... (Review)
Review
UNLABELLED
Historically, the circulation was thought to be the primary source of androgens influencing skeletal muscle. However, a growing body of research indicates that skeletal muscle expresses several androgen-synthesizing enzymes, including 5α-reductase. The intramuscular expression of these enzymes suggests that skeletal muscle is capable of synthesizing bioactive androgens, which could induce myotrophic effects via intracrine action.
PURPOSE
The aim of this brief review is to discuss recent research related to the intracrine and myotrophic roles of androgens, with particular focus on 5α-reductase as a myotrophic mediator.
METHODS
Included in the review are 17 reviews and 58 original studies that were identified by a systematic review from MEDLINE and deemed particularly relevant to our purpose. Results are summarized to provide an overview of 5α-reductase as a mediator of the myotrophic effects of androgens. In particular, discussions are included regarding androgen biosynthesis and androgen signaling within skeletal muscle, the effects of exercise on intramuscular androgen biosynthesis, and clinical applications of androgens and of a new class of myotrophic agonists termed selective androgen receptor modulator.
RESULTS
The ability of several peripheral tissues to synthesize bioactive androgens is well documented in the literature. Herein, we summarize newer studies that demonstrate that 1) skeletal muscle has the capability to synthesize both testosterone and dihydrotestosterone from dehydroepiandrosterone, which is present in abundance within the circulation, and 2) that exercise increases the expression of certain androgen-biosynthesizing enzymes within muscle.
CONCLUSIONS
Intramuscularly synthesized androgens have the potential to influence skeletal muscle via intracrine action; however, their exact role in skeletal muscle development and maintenance requires further elucidation.
Topics: Androgens; Animals; Cholestenone 5 alpha-Reductase; Humans; Muscle, Skeletal; Signal Transduction
PubMed: 21988936
DOI: 10.1249/MSS.0b013e31823bfcbf -
International Journal of Molecular... Dec 2022Androgens such as testosterone and dihydrotestosterone (DHT) are essential for male sexual development, masculinisation, and fertility. Testosterone is produced via the... (Review)
Review
Androgens such as testosterone and dihydrotestosterone (DHT) are essential for male sexual development, masculinisation, and fertility. Testosterone is produced via the canonical androgen production pathway and is essential for normal masculinisation and testis function. Disruption to androgen production can result in disorders of sexual development (DSD). In the canonical pathway, 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) is viewed as a critical enzyme in the production of testosterone, performing the final conversion required. HSD17B3 deficiency in humans is associated with DSD due to low testosterone concentration during development. Individuals with mutations have poorly masculinised external genitalia that can appear as ambiguous or female, whilst having internal Wolffian structures and testes. Recent studies in mice deficient in HSD17B3 have made the surprising finding that testosterone production is maintained, male mice are masculinised and remain fertile, suggesting differences between mice and human testosterone production exist. We discuss the phenotypic differences observed and the possible other pathways and enzymes that could be contributing to testosterone production and male development. The identification of alternative testosterone synthesising enzymes could inform the development of novel therapies to endogenously regulate testosterone production in individuals with testosterone deficiency.
Topics: Humans; Male; Female; Mice; Animals; Testosterone; Androgens; Virilism; Mutation; Dihydrotestosterone; 17-Hydroxysteroid Dehydrogenases
PubMed: 36555196
DOI: 10.3390/ijms232415555