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Biomolecules Nov 2022Androgens are steroids that modulate various processes in the body, ranging from reproduction, metabolism, and even immune response. The main androgens are testosterone,... (Review)
Review
Androgens are steroids that modulate various processes in the body, ranging from reproduction, metabolism, and even immune response. The main androgens are testosterone, dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA). These steroids modulate the development and function of immune response cells. Androgens are generally attributed to immunosuppressive effects; however, this is not always the case. Variations in the concentrations of these hormones induce differences in the innate, humoral, and cell-mediated immune response, which is concentration dependent. The androgens at the highest concentration in the organism that bind to the androgen receptor (AR) are DHEA and testosterone. Therefore, in this work, we review the effects of DHEA and testosterone on the immune response. The main findings of this review are that DHEA and testosterone induce similar but also opposite effects on the immune response. Both steroids promote the activation of regulatory T cells, which suppresses the Th17-type response. However, while testosterone suppresses the inflammatory response, DHEA promotes it, and this modulation is important for understanding the involvement of androgens in infectious (bacterial, viral and parasitic) and autoimmune diseases, as well as in the sexual dimorphism that occurs in these diseases.
Topics: Testosterone; Dehydroepiandrosterone; Androgens; Dihydrotestosterone; Adaptive Immunity
PubMed: 36551196
DOI: 10.3390/biom12121768 -
British Medical Journal (Clinical... Jul 1983
Topics: Addison Disease; Dihydrotestosterone; Female; Humans
PubMed: 6409260
DOI: 10.1136/bmj.287.6386.216-a -
The Journal of Clinical Investigation Dec 1984Feminization in men occurs when the effective ratio of androgen to estrogen is lowered. Since sufficient estrogen is produced in normal men to induce breast enlargement...
Feminization in men occurs when the effective ratio of androgen to estrogen is lowered. Since sufficient estrogen is produced in normal men to induce breast enlargement in the absence of adequate amounts of circulating androgens, it has been generally assumed that androgens exert an antiestrogenic action to prevent feminization in normal men. We examined the mechanisms of this effect of androgens in the mouse breast. Administration of estradiol via silastic implants to castrated virgin CBA/J female mice results in a doubling in dry weight and DNA content of the breast. The effect of estradiol can be inhibited by implantation of 17 beta-hydroxy-5 alpha-androstan-3-one (dihydrotestosterone), whereas dihydrotestosterone alone had no effect on breast growth. Estradiol administration also enhances the level of progesterone receptor in mouse breast. Within 4 d of castration, the progesterone receptor virtually disappears and estradiol treatment causes a twofold increase above the level in intact animals. Dihydrotestosterone does not compete for binding to the progesterone receptor, but it does inhibit estrogen-mediated increases of progesterone receptor content of breast tissue cytosol from both control mice and mice with X-linked testicular feminization (tfm)/Y. Since tfm/Y mice lack a functional androgen receptor, we conclude that this antiestrogenic action of androgen is not mediated by the androgen receptor. Dihydrotestosterone competes with estradiol for binding to the cytosolic estrogen receptor of mouse breast, whereas 17 beta-hydroxy-5 beta-androstan-3-one (5 beta-dihydrotestosterone) neither competes for binding nor inhibits estradiol-mediated induction of the progesterone receptor. Dihydrotestosterone also promotes the translocation of estrogen receptor from cytoplasm to nucleus; the ratio of cytoplasmic-to-nuclear receptor changes from 3:1 in the castrate to 1:2 in dihydrotestosterone-treated mice. Thus, the antiestrogenic effect of androgen in mouse breast may be the result of effects of dihydrotestosterone on the estrogen receptor. If so, dihydrotestosterone performs one of its major actions independent of the androgen receptor.
Topics: Animals; Binding, Competitive; Castration; Centrifugation, Density Gradient; Dihydrotestosterone; Estradiol; Female; Mammary Glands, Animal; Mice; Mice, Inbred CBA; Promegestone; Receptors, Estrogen; Testosterone
PubMed: 6542571
DOI: 10.1172/JCI111654 -
Fertility and Sterility Mar 1989In order to produce a sustained release system for natural androgens, two groups of six hypogonadal males received intramuscular (IM) 40 mg crystalline...
In order to produce a sustained release system for natural androgens, two groups of six hypogonadal males received intramuscular (IM) 40 mg crystalline dihydrotestosterone (DHT), either with particle size of less than 50 microns (DHT-M) or between 100 and 150 microns (DHT-C). Serum DHT was analyzed through 51 days of follow-up. In the DHT-M group, serum DHT was above pretreatment values for 17 days, whereas in the DHT-C group, this period was extended over 50 days. The area under the serum concentration-time curve and the half-life of absorption calculated for the DHT-C group were greater than those obtained for the DHT-M group (55.1 ng/day/ml and 21 days vs. 14.5 ng/day/ml and 6 days; P less than 0.01). The authors conclude that DHT injection appears to be an effective and convenient technique for restoring serum physiologic DHT levels. This approach is suitable for long-term substitution therapy.
Topics: Absorption; Adult; Delayed-Action Preparations; Dihydrotestosterone; Half-Life; Humans; Hypogonadism; Injections, Intramuscular; Male; Radioimmunoassay
PubMed: 2920848
DOI: 10.1016/s0015-0282(16)60560-5 -
PloS One 2015Steroids metabolism plays an important role in mammals and contributes to quality of pig meat. The main objective of this study was to identify metabolites of...
Steroids metabolism plays an important role in mammals and contributes to quality of pig meat. The main objective of this study was to identify metabolites of androstenone, 17β-estradiol and dihydrotestosterone using primary cultured pig hepatocytes as a model system. The role of 3β-hydroxysteroid dehydrogenase (3βHSD) in regulation of steroid metabolism was also validated using trilostane, a specific 3βHSD inhibitor. Steroid glucuronide conjugated metabolites were detected by liquid chromatography time of flight mass spectrometry (LC-TOF-MS). 3βHSD enzyme was essential for metabolism of androstenone to 5α-androst-16-en-3β-ol, which then formed androstenone glucuronide conjugate. Metabolism of 17β-estradiol was accompanied by formation of glucuronide-conjugated estrone and glucuronide-conjugated estradiol. The ratio of the two metabolites was around 5:1. 3βHSD enzyme was not involved in 17β-estradiol metabolism. 5α-Dihydrotestosterone-17β-glucuronide was identified as a dihydrotestosterone metabolite, and this metabolism was related to 3βHSD enzyme activity as demonstrated by inhibition study.
Topics: 3-Hydroxysteroid Dehydrogenases; Androstenes; Animals; Cells, Cultured; Dihydrotestosterone; Estradiol; Hepatocytes; Swine
PubMed: 25590624
DOI: 10.1371/journal.pone.0113194 -
Physiological Genomics Nov 2008Androgens have been postulated to be important modulators of adipose tissue metabolism and fat cell function. In the present study, we investigated the response of male...
Androgens have been postulated to be important modulators of adipose tissue metabolism and fat cell function. In the present study, we investigated the response of male and female mice retroperitoneal adipose tissue to the nonaromatizable androgen dihydrotestosterone (DHT). Adipose tissue samples were obtained in gonadectomized animals treated with vehicle (control group), or injected with 0.1 mg DHT 1, 3, 6, 12, 18, and 24 h prior to necropsy. Fourteen animals were pooled at each time point (total 196 animals). Transcripts that were significantly modulated were considered as androgen-responsive genes. Quantitative real-time RT-PCR was used to confirm results from the microarray analysis in a subset of 46 probe sets in male mice and 98 probe sets in female mice. Considering peak time vs. control, we confirmed 74.0 and 63.3% of the modulated genes by PCR in males and females, respectively. Four genes were significantly stimulated in a similar manner by DHT in both sexes, namely metallothionein 1, growth arrest and DNA-damage-inducible 45 gamma, cyclin-dependent kinase inhibitor 1A, and fk506-binding protein 5. All these genes appear to be involved in the regulation of adipocyte differentiation/proliferation and adipogenesis. In conclusion, this study, which evaluated the acute transcriptome response of adipose tissue to DHT in male and female mice, suggests that DHT consistently modulates genes involved in the regulation of adipogenesis in retroperitoneal adipose tissue of both male and female animals.
Topics: Adipose Tissue; Animals; Dihydrotestosterone; Female; Gene Expression Profiling; Male; Mice; Mice, Inbred C57BL; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 18728228
DOI: 10.1152/physiolgenomics.00257.2007 -
La Semaine Des Hopitaux : Organe Fonde... Dec 1976
Topics: Adolescent; Adult; Dihydrotestosterone; Gynecomastia; Humans; Male; Middle Aged
PubMed: 191926
DOI: No ID Found -
Australian Veterinary Journal 2003
Review
Topics: Adrenocortical Hyperfunction; Aminoglutethimide; Animals; Bromocriptine; Cyproheptadine; Dihydrotestosterone; Dog Diseases; Dogs; Etomidate; Ketoconazole; Metyrapone; Mitotane; Selegiline
PubMed: 15084005
DOI: 10.1111/j.1751-0813.2003.tb11415.x -
Journal of the American Veterinary... Oct 2011
Topics: Adrenocortical Hyperfunction; Animals; Antineoplastic Agents; Dihydrotestosterone; Dog Diseases; Female; Male
PubMed: 21985343
DOI: 10.2460/javma.239.8.1048 -
Molecular and Cellular Endocrinology Feb 2014Medroxyprogesterone acetate (MPA) has widely been used in hormone replacement therapy (HRT), and is associated with an increased risk of breast cancer, possibly due to...
Medroxyprogesterone acetate (MPA) has widely been used in hormone replacement therapy (HRT), and is associated with an increased risk of breast cancer, possibly due to disruption of androgen receptor (AR) signaling. In contrast, the synthetic HRT Tibolone does not increase breast density, and is rapidly metabolized to estrogenic 3α-OH-tibolone and 3β-OH-tibolone, and a delta-4 isomer (Δ(4)-TIB) that has both androgenic and progestagenic properties. Here, we show that 5α-dihydrotestosterone (DHT) and Δ(4)-TIB, but not MPA, stabilize AR protein levels, initiate specific AR intramolecular interactions critical for AR transcriptional regulation, and increase proliferation of AR positive MDA-MB-453 breast cancer cells. Structural modeling and molecular dynamic simulation indicate that Δ(4)-TIB induces a more stable AR structure than does DHT, and MPA a less stable one. Microarray expression analyses confirms that the molecular actions of Δ(4)-TIB more closely resembles DHT in breast cancer cells than either ligand does to MPA.
Topics: Androgens; Biotransformation; Cell Line, Tumor; Dihydrotestosterone; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Medroxyprogesterone Acetate; Molecular Dynamics Simulation; Neoplasm Proteins; Norpregnanes; Norpregnenes; Oligonucleotide Array Sequence Analysis; Receptors, Androgen; Structure-Activity Relationship
PubMed: 24239616
DOI: 10.1016/j.mce.2013.11.002