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https://www.readbyqxmd.com/read/29682196/testosterone-metabolites-inhibit-proliferation-of-castration-and-therapy-resistant-prostate-cancer
#1
Felix Bremmer, Hubertus Jarry, Valerie Unterkircher, Silke Kaulfuss, Peter Burfeind, Heinz-Joachim Radzun, Philipp Ströbel, Paul Thelen
Novel treatments for castration-resistant prostate cancer (CRPC) such as abiraterone acetate (AA) or enzalutamide effectively target the androgen pathway to arrest aberrant signalling and cell proliferation. Testosterone is able to inhibit tumour cell growth in CRPC. Estrogen receptor-beta (ERβ) binds the testosterone-metabolites 3β-androstanediol and 3α-androstanediol in parallel to the canonical estradiol. In the prostate it is widely accepted that ERβ regulates estrogen signalling, mediating anti-proliferative effects...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29674118/germline-variant-in-hsd3b1-1245-a-c-and-response-to-abiraterone-acetate-plus-prednisone-in-men-with-new-onset-metastatic-castration-resistant-prostate-cancer
#2
Andrew W Hahn, David M Gill, Roberto H Nussenzveig, Austin Poole, Jim Farnham, Lisa Cannon-Albright, Neeraj Agarwal
BACKGROUND: The HSD3B1 gene encodes the enzyme 3β-hydroxysteroid dehydrogenase-1 (3βHSD1), which catalyzes adrenal androgen precursors into dihydrotestosterone, the most potent androgen. Recently, the HSD3B1 (1245C) variant was shown to predict shorter duration of response to androgen deprivation therapy with medical or surgical castration in the setting of castration-sensitive prostate cancer (CSPC). The HSD3B1 (1245C) variant also predicts longer duration of response to ketoconazole in men with castration-resistant prostate cancer (CRPC)...
March 27, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29673241/effect-of-acute-mid-intensity-treadmill-exercise-on-the-androgen-hormone-level-and-uncoupling-protein-1-expression-in-brown-fat-tissue-of-mouse
#3
Nahyun Kim, Jisu Kim, Choongsung Yoo, Kiwon Lim, Takayuki Akimoto, Jonghoon Park
PURPOSE: Brown adipose tissue (BAT) plays an important role in metabolizing different substances, including androgens. The aim of this study was to determine whether a single bout of aerobic exercise would increase the androgen hormone concentration in mouse BAT and whether its increase was associated with uncoupling protein-1 (UCP-1), protein kinase A (PKA)-related mechanism in BAT. METHODS: Twenty, 9-week-old ICR adult male micewere randomly divided into three groups: Control (n=6, CON), Exercise (n=7, EX), and Exercise + SRD5A1A2 inhibitor (n=7, EXIN)...
March 30, 2018: Journal of Exercise Nutrition & Biochemistry
https://www.readbyqxmd.com/read/29671886/serum-androgens-and-risk-of-atrial-fibrillation-in-older-men-the-cardiovascular-health-study
#4
Michael A Rosenberg, Molly M Shores, Alvin M Matsumoto, Petra Bůžková, Leslie A Lange, Richard A Kronmal, Susan R Heckbert, Kenneth J Mukamal
BACKGROUND: Decline in serum androgens is common among older men and has been associated with cardiovascular disease, although its role in risk of atrial fibrillation (AF) has not been well defined. HYPOTHESIS: Low serum androgens are associated with an increased risk of AF. METHODS: We examined the prospective associations between testosterone, its more active metabolite dihydrotestosterone (DHT), and sex-hormone binding globulin (SHBG) with risk of AF among 1019 otherwise healthy men of average age 76...
April 19, 2018: Clinical Cardiology
https://www.readbyqxmd.com/read/29670181/regulation-of-masculinization-androgen-signalling-for-external-genitalia-development
#5
REVIEW
Shoko Matsushita, Kentaro Suzuki, Aki Murashima, Daiki Kajioka, Alvin Resultay Acebedo, Shinichi Miyagawa, Ryuma Haraguchi, Yukiko Ogino, Gen Yamada
The biology of masculinization is fundamentally important for understanding the embryonic developmental processes that are involved in the development of the male reproductive tract, external genitalia, and also the tumorigenesis of prostate cancer. The molecular mechanisms of masculinization are of interest to many researchers and clinicians involved in varied fields, including molecular developmental biology, cancer research, endocrinology, and urology. Androgen signalling is mediated by the nuclear androgen receptor, which has fundamental roles in masculinization during development...
April 18, 2018: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29666834/androgen-action-in-prostate-function-and-disease
#6
REVIEW
Partha P Banerjee, Subhadra Banerjee, Terry R Brown, Barry R Zirkin
Benign prostatic hyperplasia (BPH) is an enlargement of the prostate gland that is frequently found in aging men. Androgens are essential for the development and differentiated function of the prostate, as well as for proliferation and survival of prostatic cells. In man, dog and rodent, there are age-related decreases in serum testosterone. Despite the lower serum testosterone levels, benign prostatic hyperplasia increases with age in men and dogs, while age-dependent prostatic hyperplasia develops in the dorsal and lateral lobes of the rat prostate...
2018: American Journal of Clinical and Experimental Urology
https://www.readbyqxmd.com/read/29666640/investigating-the-interactive-effects-of-sex-steroid-hormones-and-brain-derived-neurotrophic-factor-during-adolescence-on-hippocampal-nmda-receptor-expression
#7
Cushla R McCarthny, Xin Du, YeeWen Candace Wu, Rachel A Hill
Sex steroid hormones have neuroprotective properties which may be mediated by brain-derived neurotrophic factor (BDNF). This study sought to determine the interactive effects of preadolescent hormone manipulation and BDNF heterozygosity (+/- ) on hippocampal NMDA-R expression. Wild-type and BDNF+/- mice were gonadectomised, and females received either 17 β -estradiol or progesterone treatment, while males received either testosterone or dihydrotestosterone (DHT) treatment. Dorsal (DHP) and ventral hippocampus (VHP) were dissected, and protein expression of GluN1, GluN2A, GluN2B, and PSD-95 was assessed by Western blot analysis...
2018: International Journal of Endocrinology
https://www.readbyqxmd.com/read/29665500/aromatase-inhibition-by-letrozole-attenuates-kainic-acid-induced-seizures-but-not-neurotoxicity-in-mice
#8
Ramsha Iqbal, Gaurav K Jain, Fouzia Siraj, Divya Vohora
Evidence shows neurosteroids play a key role in regulating epileptogenesis. Neurosteroids such as testosterone modulate seizure susceptibility through its transformation to metabolites which show proconvulsant and anticonvulsant effects, respectively. Reduction of testosterone by aromatase generates proconvulsant 17-β estradiol. Alternatively, testosterone is metabolized into 5α-dihydrotestosterone (5α-DHT) by 5α-reductase, which is then reduced by 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR) to form anticonvulsant metabolite 3α-androstanediol (3α-Diol), a potent GABAA receptor modulating neurosteroid...
April 9, 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29642629/17%C3%AE-hydroxysteroid-dehydrogenase-type-2-expression-is-induced-by-androgen-signaling-in-endometrial-cancer
#9
Chiaki Hashimoto, Yasuhiro Miki, Sota Tanaka, Kiyoshi Takagi, Misaki Fue, Zhulanqiqige Doe, Bin Li, Nobuo Yaegashi, Takashi Suzuki, Kiyoshi Ito
Endometrial cancer is one of the most common female pelvic cancers and has been considered an androgen-related malignancy. Several studies have demonstrated the anti-cell proliferative effect of androgen on endometrial cancer cells; however, the mechanisms of the anti-cancer effect of androgen remain largely unclear. 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2), which catalyzes the conversion of E2 to E1, is known to be upregulated by androgen treatment in breast cancer cells. In this study, we therefore focused on the role of androgen on estrogen dependence in endometrial cancer...
April 10, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29610568/longer-ta-repeat-but-not-v89l-polymorphisms-in-the-srd5a2-gene-may-confer-acne-risk-in-the-chinese-population
#10
Xue Hu, Wei Ding, Xinye Jin, Jia Wang, Dajin Zou, Yue Chen
Introduction: Several studies have reported that the V89L and TA repeat polymorphisms [(TA)n] of the SRD5A2 gene were associated with SRD5A2 activity. The activity of dihydrotestosterone, which is converted from testosterone by SRD5A2, is responsible for sebum secretion and the formation of acne. We hypothesized that abnormalities in SRD5A2 action could contribute to the formation of acne. Aim: To study whether the structural change of the SRD5A2 gene may affect the risk of acne in patients with normal serum testosterone levels...
February 2018: Postȩpy Dermatologii i Alergologii
https://www.readbyqxmd.com/read/29602798/hepatic-abundance-and-activity-of-androgen-and-drug-metabolizing-enzyme-ugt2b17-are-associated-with-genotype-age-and-sex
#11
Deepak Kumar Bhatt, Abdul Basit, Haeyoung Zhang, Andrea Gaedigk, Seung-Been Lee, Katrina G Claw, Aanchal Mehrotra, Amarjit S Chaudhry, Robin E Pearce, Roger Gaedigk, Ulrich Broeckel, Timothy A Thornton, Deborah A Nickerson, Erin G Schuetz, John Amory, J Steven Leeder, Bhagwat Prasad
The major objective of this study was to investigate association of genetic and non-genetic factors with variability in protein abundance and in vitro activity of the androgen metabolizing enzyme, UGT2B17, in human liver microsomes (n=455). UGT2B17 abundance was quantified by LC-MS/MS proteomics and enzyme activity was determined by using testosterone and dihydrotestosterone as in vitro probe substrates. Genotyping or gene resequencing and mRNA expression were also evaluated. Multivariate analysis was used to test association of UGT2B17 copy number variation, single nucleotide polymorphisms (SNPs), age and sex with its mRNA expression, abundance and activity...
March 30, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29601859/perfluoroalkylated-substances-pfas-affect-neither-estrogen-and-androgen-receptor-activity-nor-steroidogenesis-in-human-cells-in-vitro
#12
Anne-Cathrin Behr, Dajana Lichtenstein, Albert Braeuning, Alfonso Lampen, Thorsten Buhrke
The perfluoroalkylated substances (PFAS) perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) are used for the fabrication of water- and dirt-repellent surfaces. The use of PFOS and PFOA was restricted due to their reprotoxic properties and their environmental persistence. Therefore, industry switches to alternative PFAS, however, in contrast to PFOA and PFOS only few toxicological data are available for their substitutes. The molecular mechanism(s) underlying reproductive toxicity of PFOA and PFOS are largely unknown...
March 27, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29599322/crosstalk-between-androgen-sensitive-and-androgen-insensitive-prostate-cancer-cells
#13
Yuta Takezawa, Kouji Izumi, Kazuaki Machioka, Hiroaki Iwamoto, Renato Naito, Tomoyuki Makino, Suguru Kadomoto, Ariunbold Natsagdorj, Yoshifumi Kadono, Evan T Keller, Jian Zhang, Atsushi Mizokami
AIM: To investigate how androgen-sensitive LNCaP cells crosstalk with androgen-insensitive DU145 or PC-3 cells. MATERIALS AND METHODS: The numbers of LNCaP cells were counted when co-cultured with DU145 or PC-3 cells and vise versa. Androgen receptor (AR) activity in LNCaP cells was examined by luciferase reporter assay after transfection with a luciferase reporter driven by PSA promoter in the presence of DU145 or PC-3 cells. Concentration of androgens in the medium was measured by liquid chromatography-mass spectrometry (LC-MS/MS)...
April 2018: Anticancer Research
https://www.readbyqxmd.com/read/29583035/a-long-term-follow-up-study-of-men-born-with-very-low-birth-weight-and-their-reproductive-hormone-profile
#14
Mats Hammar, Erika Larsson, Marie Bladh, Orvar Finnström, P O Gäddlin, Ingemar Leijon, Elvar Theodorsson, Gunilla Sydsjö
Environmental factors during the fetal period may adversely affect reproductive functions in men being born with very low birth weight (VLBW, <1500 g). The objective of this prospective, controlled cohort study was to investigate if VLBW men have an altered reproductive hormone profile compared with men born at term. The study group initially consisted of all VLBW boys live-born between 1 February 1987 and 30 April 1988 in the south-east region of Sweden (n = 47). A control child was chosen born at term, at the same hospital, with the same parity, without malformations, and next in order after each VLBW child who survived the first four weeks (n = 45)...
March 27, 2018: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/29580912/usefulness-of-pharmacokinetic-efficacy-analysis-of-an-investigational-kisspeptin-analog-tak-448-in-quantitatively-evaluating-anti-tumor-growth-effect-in-the-rat-vcap-androgen-sensitive-prostate-cancer-model
#15
Kaori Ishikawa, Akira Tanaka, Akifumi Kogame, Tatsuya Watanabe, Yoshihiko Tagawa, Hisanori Matsui
TAK-448 is a kisspeptin analog with improved in vivo potency. In our previous studies in the rat JDCaP prostate cancer model, TAK-448 showed more rapid and profound reductions in plasma testosterone (T) and prostate-specific antigen (PSA, a biomarker of prostate tumor growth) levels than the gonadotropin releasing hormone (GnRH) analog leuprolide (TAP-144); however, its effects on tumor volume and subsequent tumor recurrence have not been elucidated fully. To overcome these challenges, we established the rat VCaP subcutaneous xenograft model replicating both the androgen-sensitive and castration-resistant phases of prostate cancer, and we performed pharmacokinetic/efficacy (PK/E) correlation analyses to compare the overall anti-tumor growth effects of TAK-448 to those of TAP-144...
March 23, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29578828/the-cellular-and-molecular-effects-of-the-androgen-receptor-agonist-cl-4as-1-on-breast-cancer-cells
#16
Mamoun Ahram, Ebtihal Mustafa, Shatha Abu Hammad, Mariam Alhudhud, Randa Bawadi, Lubna Tahtamouni, Faisal Khatib, Malek Zihlif
PURPOSE: The androgen receptor (AR) has attracted attention in the treatment of breast cancer. Due to the undesirable side effects of AR agonists, attempts have been undertaken to develop selective AR modulators. One of these compounds is Cl-4AS-1. This study examined this compound more closely at the cellular and molecular levels. METHODS: Three different breast cancer cell lines were utilized, namely the luminal MCF-7 cells, the molecular apocrine MDA-MB-453 cells, and the triple negative, basal MDA-MB-231 cells...
March 26, 2018: Endocrine Research
https://www.readbyqxmd.com/read/29565738/maternal-androgen-excess-and-obesity-induce-sexually-dimorphic-anxiety-like-behavior-in-the-offspring
#17
Maria Manti, Romina Fornes, Xiaojuan Qi, Elin Folmerz, Angelica Lindén Hirschberg, Thais de Castro Barbosa, Manuel Maliqueo, Anna Benrick, Elisabet Stener-Victorin
Maternal polycystic ovary syndrome (PCOS), a condition associated with hyperandrogenism, is suggested to increase anxiety-like behavior in the offspring. Because PCOS is closely linked to obesity, we investigated the impact of an adverse hormonal or metabolic maternal environment and offspring obesity on anxiety in the offspring. The obese PCOS phenotype was induced by chronic high-fat-high-sucrose (HFHS) consumption together with prenatal dihydrotestosterone exposure in mouse dams. Anxiety-like behavior was assessed in adult offspring with the elevated-plus maze and open-field tests...
March 22, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29549490/androgen-modulation-of-wnt-%C3%AE-catenin-signaling-in-androgenetic-alopecia
#18
REVIEW
A Premanand, B Reena Rajkumari
Androgenetic alopecia (AGA) is a dermatological disorder of scalp hair loss characterized by a progressive miniaturization of hair follicles with shortened anagen phase leading to a decreased number of hairs on the scalp. It is a complex polygenic trait prevailing around two-thirds of the male population. Elevated expressions of 5α-dihydrotestosterone and androgen receptor are the causal factors for AGA. This review describes recent studies on the role of androgens and androgen receptor (AR) transactivation activity in modulating the Wnt/β-catenin signaling in the dermal papilla cells of the balding scalp in androgenetic alopecia...
March 16, 2018: Archives of Dermatological Research
https://www.readbyqxmd.com/read/29544191/steroid-5%C3%AE-reductase-2-deficiency-leads-to-reduced-dominance-related-and-impulse-control-behaviors
#19
Laura J Mosher, Sean C Godar, Marc Morissette, Kenneth M McFarlin, Simona Scheggi, Carla Gambarana, Stephen C Fowler, Thérèse Di Paolo, Marco Bortolato
The enzyme steroid 5α-reductase 2 (5αR2) catalyzes the conversion of testosterone into the potent androgen 5α-dihydrotestosterone. Previous investigations showed that 5αR2 is expressed in key brain areas for emotional and socio-affective reactivity, yet the role of this enzyme in behavioral regulation remains mostly unknown. Here, we profiled the behavioral characteristics of 5αR2 heterozygous (HZ) and knockout (KO) mice, as compared with their wild-type (WT) littermates. While male 5αR2 KO mice displayed no overt alterations in motoric, sensory, information-processing and anxiety-related behaviors, they exhibited deficits in neurobehavioral correlates of dominance (including aggression against intruders, mating, and tube dominance) as well as novelty-seeking and risk-taking responses...
February 16, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29541409/inhibition-of-dihydrotestosterone-synthesis-in-prostate-cancer-by-combined-frontdoor-and-backdoor-pathway-blockade
#20
Michael V Fiandalo, John J Stocking, Elena A Pop, John H Wilton, Krystin M Mantione, Yun Li, Kristopher M Attwood, Gissou Azabdaftari, Yue Wu, David S Watt, Elizabeth M Wilson, James L Mohler
Androgen deprivation therapy (ADT) is palliative and prostate cancer (CaP) recurs as lethal castration-recurrent/resistant CaP (CRPC). One mechanism that provides CaP resistance to ADT is primary backdoor androgen metabolism, which uses up to four 3α-oxidoreductases to convert 5α-androstane-3α,17β-diol (DIOL) to dihydrotestosterone (DHT). The goal was to determine whether inhibition of 3α-oxidoreductase activity decreased conversion of DIOL to DHT. Protein sequence analysis showed that the four 3α-oxidoreductases have identical catalytic amino acid residues...
February 16, 2018: Oncotarget
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