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Endocrinology Mar 1988To determine the role of 5 alpha-dihydrotestosterone (DHT; 17 beta-hydroxy-5 alpha-androstan-3-one) in formation of the embryonic prostate, we quantitated prostatic...
To determine the role of 5 alpha-dihydrotestosterone (DHT; 17 beta-hydroxy-5 alpha-androstan-3-one) in formation of the embryonic prostate, we quantitated prostatic development in urogenital tracts of control male newborn and offspring of rats treated with a specific 5 alpha-reductase inhibitor (L652,931; Merck, Sharp, and Dohme) during prostate morphogenesis. Treatment with the 5 alpha-reductase inhibitor (50 mg/kg.day) from days 14-22 of gestation impaired development of the prostate and virilization of the external genitalia in male offspring compared to those in control animals. However, virilization of the internal genitalia (seminal vesicles, epididymis) was unaffected. Simultaneous administration of DHT (50 mg/kg.day) with the 5 alpha-reductase inhibitor restored prostate development and anogenital distances of males to normal and virilized the external genitalia of females. We conclude that DHT is the active androgen responsible for prostatic development in the rat.
Topics: 5-alpha Reductase Inhibitors; Animals; Dihydrotestosterone; Female; Male; Maternal-Fetal Exchange; Pregnancy; Prostate; Rats; Rats, Inbred Strains; Urogenital System; Wolffian Ducts
PubMed: 3342749
DOI: 10.1210/endo-122-3-1159 -
Journal of Chromatography. B,... Jul 2018Androgens play a vital role in prostate cancer development, and their elimination and blockade are essential in the disease management. DHT is the key ligand for...
Androgens play a vital role in prostate cancer development, and their elimination and blockade are essential in the disease management. DHT is the key ligand for androgen receptor (AR) in the prostate. It is locally synthesized from testosterone. In the prostate, DHT is predominantly metabolized to α-diol and β-diol. Recent studies indicate that impaired DHT catabolism is associated with prostate cancer, signifying the necessity of a sensitive quantitative method for the determination of DHT and its metabolites. In this work, an LC-MS/MS method for the simultaneous quantification of DHT and its metabolites was developed and validated. Steroid-free sera were prepared and used for the preparation of sera calibrators and quality controls (QCs). DHT and its metabolites along with their respective stable heavy isotope labeled analytes representing internal standards were first extracted with methyl tertiary-butyl ether (MTBE) and derivatized with picolinic acid (PA). The derivatized analytes were then extracted again with MTBE, dried under nitrogen and reconstituted in the mobile phase (80% methanol and 0.2% formic acid in water). Baseline chromatographic separation of the derivatized analytes was achieved isocratically on XTerra C18 column (2.1 × 100 mm) using the mobile phase at a flow rate of 0.25 mL/min. Quantitation was performed using multiple-reaction-monitoring mode with positive electrospray ionization. The method has calibration ranges from 0.0500 ng/mL to 50.0 ng/mL for DHT and its two metabolites with acceptable assay precision, accuracy, recovery, and matrix factor. It was applied to the determination of DHT and its metabolites in an animal study.
Topics: Animals; Chromatography, Liquid; Dihydrotestosterone; Linear Models; Male; Mice; Picolinic Acids; Prostatic Neoplasms; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry
PubMed: 29778874
DOI: 10.1016/j.jchromb.2018.05.008 -
The Prostate Aug 1998Gene-regulated mechanisms govern tumor development, but the actual development of tumors can be suppressed or promoted by epigenetic factors. Lobund-Wistar (L-W) rats...
BACKGROUND
Gene-regulated mechanisms govern tumor development, but the actual development of tumors can be suppressed or promoted by epigenetic factors. Lobund-Wistar (L-W) rats are genetically predisposed to development of spontaneous and induced metastasizing moderately differentiated adenocarcinomas in the prostate-seminal vesicle (P-SV) complex. In L-W rats with one slow-release subcutaneous implant of dihydrotestosterone (DHT) (5alpha-Androstan-17beta-ol-3-one), the development of induced P-SV tumors 14 months later was significantly suppressed, with involution of testes, aspermia, and absence of detectable serum testosterone. The tumor-suppressive effect of DHT was confirmed. Spontaneous P-SV tumors developed in 57 of 220 control L-W rats (26%) at an average age 20 months.
METHODS
At age 12 months, 70 L-W rats were administered an implant of 40 mg of DHT, and 75 untreated rats served as controls. All rats that developed palpable P-SV tumors were autopsied, and surviving rats were autopsied at age 24 months.
RESULTS
At age 24 months, 9 of 70 DHT-treated rats (12.8%) and 20 of 75 DHT-free control rats (26.6%) had developed P-SV tumors spontaneously at average age 20.5 and 20 months, respectively.
CONCLUSIONS
Slow-release implants of DHT administered to L-W rats at age 12 months reduced by 50% the development of spontaneous P-SV tumors by age 24 months.
Topics: Adenocarcinoma; Aging; Animals; Delayed-Action Preparations; Dihydrotestosterone; Male; Prostatic Neoplasms; Rats; Rats, Wistar; Seminal Vesicles
PubMed: 9687988
DOI: 10.1002/(sici)1097-0045(19980801)36:3<168::aid-pros4>3.0.co;2-d -
Polski Merkuriusz Lekarski : Organ... Dec 2008In the prostate the enzyme 5alpha-reductase converts testosterone into more active form--dihydrotestosterone (DHT). This hormone strongly influences prostate function... (Review)
Review
In the prostate the enzyme 5alpha-reductase converts testosterone into more active form--dihydrotestosterone (DHT). This hormone strongly influences prostate function and takes part in its pathology Since the connection between androgens and pathology of this gland has been proved, pharmacological inhibition of conversion became one of the therapy strategies both for benign prostate hyperplasia and prostate cancer. Last decade has brought numerous, long term clinical trials which involved numerous men being administered finasteride and other 5alpha-reductase inhibitors in bening prostate hypertrophy (BPH) treatment and prostate cancer (PCa) prevention. The results confirmed main assumptions, however revealed complex androgens and other factors' activity overlapping with the effect of therapy on prostate disease.
Topics: Dihydrotestosterone; Enzyme Inhibitors; Finasteride; Humans; Male; Oxidoreductases; Prostatic Diseases; Prostatic Hyperplasia
PubMed: 19205388
DOI: No ID Found -
FEBS Letters Mar 2022The mechanisms through which the androgen-dependent activation of the androgen receptor (AR) regulates gravid uterine ferroptosis remain unknown. We show that while...
The mechanisms through which the androgen-dependent activation of the androgen receptor (AR) regulates gravid uterine ferroptosis remain unknown. We show that while co-exposure of pregnant rats to the androgen 5α-dihydrotestosterone (DHT) and insulin (INS) triggered uterine ferroptotic signaling cascades, additional treatment with the anti-androgen flutamide increased expression of the key ferroptosis-inhibitory proteins SLC7A11, GSH, and GPX4; reduced iron content; normalized levels of ferroptosis-associated Tfrc, Fpn1, and Ho1 mRNAs; reduced levels of proteins modified by 4-HNE (a marker of ferroptosis); and restored protein levels of NRF2, a key transcription factor regulating antioxidant defense signaling, in the gravid uterus. Furthermore, exposure to DHT alone increased uterine ferroptosis, and NRF2 abundance was negatively correlated with AR status. Co-immunoprecipitation and Western blot assays revealed that the AR physically interacted with endogenous NRF2, and this interaction was increased by DHT exposure in vivo. Our results suggest that AR overactivation and NRF2 suppression cooperate in the regulation of NRF2-targets in uterine ferroptosis.
Topics: Androgens; Animals; Dihydrotestosterone; Female; Ferroptosis; NF-E2-Related Factor 2; Pregnancy; Rats; Receptors, Androgen; Signal Transduction; Uterus
PubMed: 35038776
DOI: 10.1002/1873-3468.14289 -
Endocrine Journal Jan 20235α-reductase type 2 (5αRD2) deficiency is a 46,XY disorder of sex development caused by impaired conversion of testosterone (T) to dihydrotestosterone (DHT). Penile...
5α-reductase type 2 (5αRD2) deficiency is a 46,XY disorder of sex development caused by impaired conversion of testosterone (T) to dihydrotestosterone (DHT). Penile enlargement therapy is important for male patients with 46,XY 5αRD2 deficiency who have undermasculinized external genitalia, such as severe micropenis. High-dose T and percutaneous DHT replacement are reportedly efficacious for penile enlargement in patients with this disorder. We presented herein the longitudinal course of four patients with 46,XY 5αRD2 deficiency who received T and DHT. T replacement therapy during infancy increased the stretched penile length (SPL) in three of the patients but was ineffective in one patient. DHT was administered to the three patients after T replacement therapy and further increased the SPL. During and after puberty, two patients asked for and received T replacement therapy, which contributed to increasing their SPL. A semen test in one patient with T replacement therapy at age 27 years revealed cryptozoospermia despite normal testicular volume. The clinical course of our patients during infancy indicated that DHT therapy may be preferrable to T replacement therapy for penile enlargement in patients with 5αRD2 deficiency. During and after puberty, T replacement therapy promoted penile enlargement possibly because of increased conversion of T to DHT via increased 5α-reductase type 1 activity even in patients in whom it was ineffective during infancy. In conclusion, DHT is effective for penile enlargement during infancy in patients with 5αRD2 deficiency while T replacement therapy is a viable option during puberty.
Topics: Humans; Male; Infant; Adult; Testosterone; Dihydrotestosterone; Puberty; Oxidoreductases; Disease Progression
PubMed: 36216557
DOI: 10.1507/endocrj.EJ22-0112 -
Journal of Labelled Compounds &... Aug 2016Imaging of androgen receptor expression in prostate cancer using F-18 FDHT is becoming increasingly popular. With the radiolabelling precursor now commercially...
Imaging of androgen receptor expression in prostate cancer using F-18 FDHT is becoming increasingly popular. With the radiolabelling precursor now commercially available, developing a fully automated synthesis of [(18) F] FDHT is important. We have fully automated the synthesis of F-18 FDHT using the iPhase FlexLab module using only commercially available components. Total synthesis time was 90 min, radiochemical yields were 25-33% (n = 11). Radiochemical purity of the final formulation was > 99% and specific activity was > 18.5 GBq/µmol for all batches. This method can be up-scaled as desired, thus making it possible to study multiple patients in a day. Furthermore, our procedure uses 4 mg of precursor only and is therefore cost-effective. The synthesis has now been validated at Austin Health and is currently used for [(18) F]FDHT studies in patients. We believe that this method can easily adapted by other modules to further widen the availability of [(18) F]FDHT.
Topics: Automation; Chemistry Techniques, Synthetic; Dihydrotestosterone; Fluorine Radioisotopes; Isotope Labeling; Quality Control; Radiochemistry
PubMed: 27378195
DOI: 10.1002/jlcr.3417 -
Nihon Rinsho. Japanese Journal of... Mar 1995
Review
Topics: Adolescent; Child; Child, Preschool; Dihydrotestosterone; Female; Humans; Infant; Infant, Newborn; Male; Methods
PubMed: 8753311
DOI: No ID Found -
Steroids Nov 1999
Topics: Androgens; Animals; Dihydrotestosterone; History, 20th Century; Humans; Male
PubMed: 10577831
DOI: 10.1016/s0039-128x(99)00054-9 -
The Journal of Pediatrics Jul 1986Four boys with persistent pubertal gynecomastia were given intramuscular dihydrotestosterone heptanoate (DHT-hp) at 2 to 4-week intervals for 16 weeks. By the end of...
Four boys with persistent pubertal gynecomastia were given intramuscular dihydrotestosterone heptanoate (DHT-hp) at 2 to 4-week intervals for 16 weeks. By the end of treatment, breast size in all four boys had decreased 67% to 78%. Initial plasma levels of gonadotropins, estradiol, testosterone, and dihydrotestosterone (DHT) were normal. Mean plasma DHT concentration rose with the injections of DHT-hp, and remained elevated throughout the treatment period. Estradiol, LH, FSH, and testosterone decreased during treatment, as did 24-hour urinary LH and FSH. No regrowth of breast tissue was observed 6 to 15 months after treatment, although hormone concentrations had returned to near pretreatment values by 2 months after the last injection. DHT-hp has potential to be an effective medical therapy for persistent pubertal gynecomastia.
Topics: Adolescent; Dihydrotestosterone; Estradiol; Follicle Stimulating Hormone; Gynecomastia; Humans; Luteinizing Hormone; Male; Puberty; Testosterone
PubMed: 3088241
DOI: 10.1016/s0022-3476(86)80596-0