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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 -
Asian Journal of Andrology Mar 2011
Topics: Aged; Bone Density; Dihydrotestosterone; Estradiol; Humans; Male; Prostate; Testosterone
PubMed: 21196939
DOI: 10.1038/aja.2010.173 -
Steroids Dec 2012We have devised an efficient procedure for the synthesis of 5α-dihydrotestosterone (DHT) (1) starting from 3β-hydroxy-5α-androstan-17-one, providing the product in...
We have devised an efficient procedure for the synthesis of 5α-dihydrotestosterone (DHT) (1) starting from 3β-hydroxy-5α-androstan-17-one, providing the product in unprecedented 82% yield. A reported method of using toxic Jones reagent is replaced by milder oxidizing agent (NMO/TPAP) in the synthesis of a key intermediate 17β-[(tert-butyldimethylsilyl)oxy]-5α-androstan-3-one (18). This new procedure is simple, does not require special apparatus/precautions or chromatographic purification in most of the steps.
Topics: Androgens; Androsterone; Cyclic N-Oxides; Dihydrotestosterone; Morpholines; Oxidation-Reduction
PubMed: 23044354
DOI: 10.1016/j.steroids.2012.09.003 -
Medicine Jul 2020Circumcision like any other surgical procedure is not devoid of complications. Serious complications are rare and include iatrogenic hypospadias, glans...
RATIONALE
Circumcision like any other surgical procedure is not devoid of complications. Serious complications are rare and include iatrogenic hypospadias, glans ischemia/necrosis, and glans amputation, all of which require an emergent treatment.
PATIENT CONCERNS
We report here a case of 6 months-old-boy with a superficial glans ischemia following circumcision.
DIAGNOSIS
Physical examination revealed a severely cyanotic glans with the moderate edema of the dorsal penile skin. Plasma levels of D-dimer were 8.57 mg/L. Urine passage was unremarkable while color Doppler ultrasonography revealed a normal blood flow.
INTERVENTIONS
The patient was successfully treated with subcutaneous injection of enoxaparin (low-molecular-weight heparin) and topical 2.5% dihydrotestosterone.
OUTCOMES
The appearance of the glans penis on the 5th day was close to normal while the control levels of D-dimer dropped to the reference range. The patient was discharged from the hospital on the 6th day. At 6-month follow-up, the appearance of the glans penis was normal.
LESSONS
Acute glans penis ischemia following circumcision is a rare complication. Its successful treatment with enoxaparin and topical dihydrotestosterone has not been previously reported in the literature.
Topics: Administration, Topical; Circumcision, Male; Dihydrotestosterone; Heparin, Low-Molecular-Weight; Humans; Infant; Ischemia; Male; Penis
PubMed: 32702932
DOI: 10.1097/MD.0000000000021340 -
Neuroendocrinology Jun 2002The pattern of growth hormone (GH) secretion is sexually dimorphic in rats. We have previously shown that the secretory pattern in adult ovariectomized (OVX) female rats...
The pattern of growth hormone (GH) secretion is sexually dimorphic in rats. We have previously shown that the secretory pattern in adult ovariectomized (OVX) female rats is masculinized by the administration of a single dose of dihydrotestosterone (DHT), a nonaromatizable androgen. To investigate the primary site of action of DHT in the brain, a small amount of DHT was injected directly into a defined area of the brain, and the blood GH profile was observed for 18 h in conscious adult OVX female rats. The bilateral direct injection of 1 microg DHT into the medial preoptic area (MPA) produced a male-like secretory pattern of GH in OVX rats. The masculinizing effects became apparent at 9 h after injection, from which time the episodic GH secretion was produced regularly at intervals of about 150 min, the amplitude of the peak increased and baseline levels were lowered. These parameters, analyzed during 9-18 h after DHT injection, were not different from those in adult male rats. On the contrary, microinjection of DHT into the bed nucleus of the stria terminalis, the hypothalamic periventricular nucleus, or the hypothalamic arcuate-ventromedial nucleus did not affect the secretory pattern of GH. The data indicate that DHT primarily acts on cells in the MPA through androgen receptors and modulates the secretion of somatostatin and/or GH-releasing hormone secondarily to masculinize the GH secretory pattern in OVX rats.
Topics: Animals; Dihydrotestosterone; Female; Growth Hormone; Kinetics; Male; Microinjections; Ovariectomy; Preoptic Area; Rats; Rats, Sprague-Dawley; Sex Characteristics
PubMed: 12065891
DOI: 10.1159/000059435 -
Physiology & Behavior 1996In the male Syrian hamster, the medial amygdaloid nucleus (Me) and medial preoptic area (MPOA) are critical for expression of male mating behavior. These regions contain... (Comparative Study)
Comparative Study
In the male Syrian hamster, the medial amygdaloid nucleus (Me) and medial preoptic area (MPOA) are critical for expression of male mating behavior. These regions contain steroid receptor-containing neurons that transduce hormonal signals essential for copulation. In castrated males bearing an intracerebral steroid implant in the MPOA, testosterone or estradiol can facilitate sexual activity. However, DHT is without effect. Testosterone can also stimulate mating when implanted in the Me. The present study determined if estradiol or DHT had behavioral activity in the Me. Twenty adult male hamsters were selected for vigorous sexual behavior. Twelve weeks after castration, sexual behavior was assessed and each male received a single intracranial implant (23-gauge tubing packed with crystalline estradiol or DHT, n = 10 each) placed stereotaxically into posterior Me (MeP). Behavior was examined after surgery to determine if androgens or estrogens in MeP could stimulate sexual behavior above that observed after castration. Mating behavior in DHT-implanted males was not significantly different from castrates. However, males with estradiol implants displayed significantly more copulatory and noncopulatory sexual activity after surgery compared to males with DHT implants. These results suggest that testosterone facilitation of mating behavior in MeP is mediated by aromatization to estradiol, and that DHT is not behaviorally active in this nucleus.
Topics: Amygdala; Animals; Cricetinae; Dihydrotestosterone; Drug Implants; Estradiol; Immunohistochemistry; Male; Mesocricetus; Orchiectomy; Sexual Behavior, Animal; Stimulation, Chemical
PubMed: 8778874
DOI: 10.1016/0031-9384(95)02204-x -
Analytical Sciences : the International... Sep 2018In this study, proton affinitive derivatization using picolinic acid and its analogs (3- and 6-methylpicolinic acid and 5-butylpicolinic acid) with proton affinitive...
In this study, proton affinitive derivatization using picolinic acid and its analogs (3- and 6-methylpicolinic acid and 5-butylpicolinic acid) with proton affinitive moieties was performed for the highly sensitive determination of testosterone (T) and 5α-dihydrotestosterone (DHT) in saliva by LC-ESI-MS/MS. T and DHT were converted to their corresponding picolinate esters and their chromatographic behavior was investigated with a reversed phase column. The picolinate ester of each steroid exhibited a clear single peak and elution occurred in the following order: picolinate, 3/6-methylpicolinate, and 5-butylpicolinate. Estimation and understanding of the separation and retention time of each picolinate ester was made simple using the develop method. Although the peaks of picolinate and 3/6-methylpicolinate esters were suppressed by interference from the saliva background (matrix effect), the 5-butylpicolinate esters were only marginally affected.
Topics: Chromatography, Liquid; Clinical Chemistry Tests; Dihydrotestosterone; Humans; Limit of Detection; Protons; Saliva; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Testosterone
PubMed: 30078816
DOI: 10.2116/analsci.18SCP08 -
Hormone Research 2001Percutaneous administration of dihydrotestosterone (DHT) has been successful in promoting phallic growth in infants and children with 5 alpha-reductase deficiency raised...
BACKGROUND
Percutaneous administration of dihydrotestosterone (DHT) has been successful in promoting phallic growth in infants and children with 5 alpha-reductase deficiency raised as males. We investigated whether percutaneous administration of DHT is similarly effective in patients with micropenis due to alternative diagnoses.
METHODS
Six patients (age range 1.9-8.3 years) with micropenis of variable etiology were studied prospectively. 2.5% DHT gel was applied to the phallus once daily at a dose of 0.15-0.33 mg/kg body weight. Serum DHT concentrations were measured at 0, 2, 4, 8, 12 and 24 h following application of DHT gel.
RESULTS
Peak DHT concentrations were attained within 2-8 h after application of the gel and subsequently remained within the normal adult range in all but 1 patient, who had received the lowest dose of 0.15 mg/kg. An increase in phallic growth, ranging from 0.5-2.0 cm, was achieved after 3-4 months of treatment in all patients whose DHT concentrations were maintained within adult range.
CONCLUSION
Percutaneous administration of DHT in a dose of 0.2-0.3 mg/kg once daily for a period of 3-4 months may be useful in the management of patients with testosterone biosynthetic defects, who have sufficient masculinization to warrant male sex assignment, or in patients with micropenis prior to reconstructive surgery.
Topics: Administration, Topical; Child; Child, Preschool; Dihydrotestosterone; Dose-Response Relationship, Drug; Gels; Humans; Infant; Kinetics; Male; Osmolar Concentration; Penile Diseases; Penis; Prospective Studies; Time Factors
PubMed: 11910204
DOI: 10.1159/000048115 -
Clinical Techniques in Small Animal... Feb 2007Pituitary-dependent hyperadrenocorticism is a common endocrine disorder in dogs in the United States. Once a diagnosis is established, a decision must be made whether or... (Review)
Review
Pituitary-dependent hyperadrenocorticism is a common endocrine disorder in dogs in the United States. Once a diagnosis is established, a decision must be made whether or not to pursue treatment, and if so, which medication to use. Historically, mitotane (Lysodren, o,p'-DDD, Bristol-Myers Squibb, New York) has been the most commonly used treatment for medical management. Its use is complicated and comes with many potential side effects, making many practitioners wary of its use. Recently, trilostane has been proven to be an effective treatment of pituitary-dependent hyperadrenocorticism and is approved for use in other countries. Treatment with trilostane is somewhat simpler and the incidence of side effects seems to be less when compared with mitotane therapy. Either treatment can be a safe and effective method of treatment for pituitary-dependent hyperadrenocorticism when the practitioner and client are well educated regarding their use and an appropriate monitoring protocol is used.
Topics: Adrenocortical Hyperfunction; Animals; Antineoplastic Agents, Hormonal; Dihydrotestosterone; Dog Diseases; Dogs; Mitotane; Safety; Treatment Outcome
PubMed: 17542193
DOI: 10.1053/j.ctsap.2007.02.003 -
Nature Biotechnology Feb 2016
Topics: Alopecia; Biotechnology; Dihydrotestosterone; Drug Discovery; Drug Industry; Female; Hair Follicle; Humans; Male; Receptors, Androgen
PubMed: 26849499
DOI: 10.1038/nbt0216-120