A selective androgen receptor modulator with minimal prostate hypertrophic activity enhances lean body mass in male rats and stimulates sexual behavior in female rats

Endocrine ◽  
2007 ◽  
Vol 32 (1) ◽  
pp. 41-51 ◽  
Author(s):  
George F. Allan ◽  
Pamela Tannenbaum ◽  
Tifanie Sbriscia ◽  
Olivia Linton ◽  
Muh-Tsann Lai ◽  
...  
Keyword(s):  
Sexual Behavior ◽  
Androgen Receptor ◽  
Lean Body Mass ◽  
Body Mass ◽  
Female Rats ◽  
Male Rats ◽  
Selective Androgen Receptor Modulator ◽  
Receptor Modulator

A selective androgen receptor modulator with minimal prostate hypertrophic activity restores lean body mass in aged orchidectomized male rats

2008 ◽  
Vol 110 (3-5) ◽  
pp. 207-213 ◽  
Author(s):  
George Allan ◽  
Tifanie Sbriscia ◽  
Olivia Linton ◽  
Muh-Tsann Lai ◽  
Donna Haynes-Johnson ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Lean Body Mass ◽  
Body Mass ◽  
Male Rats ◽  
Selective Androgen Receptor Modulator ◽  
Receptor Modulator

Computed tomographic assessment of lean body mass in patients on selective androgen receptor modulator

2020 ◽  
Vol 59 (2) ◽  
pp. 100-103
Author(s):  
Richard Thomas ◽  
Atul B. Shinagare ◽  
Michael H. Rosenthal ◽  
Brandon Lee ◽  
Heather A. Jacene ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Lean Body Mass ◽  
Body Mass ◽  
Selective Androgen Receptor Modulator ◽  
Computed Tomographic ◽  
Receptor Modulator

scholarly journals Amelioration of sexual behavior and motor activity deficits in a castrated rodent model with a selective androgen receptor modulator SARM-2f

PLoS ONE ◽  
2017 ◽  
Vol 12 (12) ◽  
pp. e0189480 ◽  
Author(s):  
Megumi Morimoto ◽  
Yuichiro Amano ◽  
Masahiro Oka ◽  
Ayako Harada ◽  
Hisashi Fujita ◽  
...  
Keyword(s):  
Sexual Behavior ◽  
Androgen Receptor ◽  
Motor Activity ◽  
Rodent Model ◽  
Selective Androgen Receptor Modulator ◽  
Receptor Modulator

scholarly journals Selective Androgen Receptor Modulator Treatment Improves Muscle Strength and Body Composition and Prevents Bone Loss in Orchidectomized Rats

Endocrinology ◽  
2005 ◽  
Vol 146 (11) ◽  
pp. 4887-4897 ◽  
Author(s):  
Wenqing Gao ◽  
Peter J. Reiser ◽  
Christopher C. Coss ◽  
Mitch A. Phelps ◽  
Jeffrey D. Kearbey ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Androgen Receptor ◽  
Muscle Mass ◽  
Male Rats ◽  
Levator Ani Muscle ◽  
Dependent Manner ◽  
Agonist Activity ◽  
Mineral Density ◽  
Selective Androgen Receptor Modulator ◽  
Receptor Modulator

The partial agonist activity of a selective androgen receptor modulator (SARM) in the prostate was demonstrated in orchidectomized rats. In the current study, we characterized the full agonist activity of S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide (a structurally related SARM referred to in other publications and hereafter as S-4) in skeletal muscle, bone, and pituitary of castrated male rats. Twelve weeks after castration, animals were treated with S-4 (3 or 10 mg/kg), dihydrotestosterone (DHT) (3 mg/kg), or vehicle for 8 wk. S-4 (3 and 10 mg/kg) restored soleus muscle mass and strength and levator ani muscle mass to that seen in intact animals. Similar changes were also observed in DHT-treated (3 mg/kg) animals. Compared with the anabolic effects observed in muscle, DHT (3 mg/kg) stimulated prostate and seminal vesicle weights moire than 2-fold greater than that observed in intact controls, whereas S-4 (3 mg/kg) returned these androgenic organs to only 16 and 17%, respectively, of the control levels. S-4 (3 and 10 mg/kg) and DHT (3 mg/kg) restored castration-induced loss in lean body mass. Furthermore, S-4 treatment caused a significantly larger increase in total body bone mineral density than DHT. S-4 (3 and 10 mg/kg) also demonstrated agonist activity in the pituitary and significantly decreased plasma LH and FSH levels in castrated animals in a dose-dependent manner. In summary, the strong anabolic effects of S-4 in skeletal muscle, bone, and pituitary were achieved with minimal pharmacologic effect in the prostate. The tissue-selective pharmacologic activity of SARMs provides obvious advantages over steroidal androgen therapy and demonstrates the promising therapeutic utility that this new class of drugs may hold.

scholarly journals Preclinical Characterization of a (S)-N-(4-Cyano-3-Trifluoromethyl-Phenyl)-3-(3-Fluoro, 4-Chlorophenoxy)-2-Hydroxy-2-Methyl-Propanamide: A Selective Androgen Receptor Modulator for Hormonal Male Contraception

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 385-395 ◽  
Author(s):  
Amanda Jones ◽  
Jiyun Chen ◽  
Dong Jin Hwang ◽  
Duane D. Miller ◽  
James T. Dalton
Keyword(s):  
Androgen Receptor ◽  
Levator Ani ◽  
Male Rats ◽  
Male Contraception ◽  
Levator Ani Muscle ◽  
Dependent Manner ◽  
Mineral Density ◽  
Intact Male ◽  
Selective Androgen Receptor Modulator ◽  
Receptor Modulator

The pharmacologic effects of (S)-N-(4-cyano-3-trifluoromethyl-phenyl)-3-(3-fluoro, 4-chlorophenoxy)-2-hydroxy-2-methyl-propanamide (S-23) were characterized in male rats as an animal model of hormonal male contraception. S-23 showed high binding affinity (inhibitory constant = 1.7 ± 0.2 nm) and was identified as a full agonist in vitro. In castrated male rats, the ED50 of S-23 in the prostate and levator ani muscle was 0.43 and 0.079 mg/d, respectively. In intact male rats treated for 14 d, S-23 alone suppressed LH levels by greater than 50% at doses greater than 0.1 mg/d, with corresponding decreases in the size of the prostate but increases in the size of levator ani muscle. In intact male rats treated for up to 10 wk with S-23 and estradiol benzoate (EB; necessary to maintain sexual behavior in rats), S-23 showed biphasic effects on androgenic tissues and spermatogenesis by suppressing serum concentrations of LH and FSH. EB alone showed no effect on spermatogenesis. In the EB + S-23 (0.1 mg/d) group, four of six animals showed no sperm in the testis and zero pregnancies (none of six) in mating trials. After termination of treatment, infertility was fully reversible, with a 100% pregnancy rate observed after 100 d of recovery. S-23 increased bone mineral density and lean mass but reduced fat mass in a dose-dependent manner. This is the first study to show that a selective androgen receptor modulator combined with EB is an effective and reversible regimen for hormonal male contraception in rats. The beneficial effects of S-23 on the muscle, tissue selectivity, and favorable pharmacokinetic properties make it a strong candidate for use in oral male contraception. An aryl-propionamide selective androgen receptor modulator (S-23) is an effective and reversible agent for hormonal male contraception in rats.

Effects of Selective Androgen Receptor Modulator (SARM) Treatment in Osteopenic Female Rats

2009 ◽  
Vol 26 (11) ◽  
pp. 2471-2477 ◽  
Author(s):  
Jeffrey D. Kearbey ◽  
Wenqing Gao ◽  
Scott J. Fisher ◽  
Di Wu ◽  
Duane D. Miller ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Female Rats ◽  
Selective Androgen Receptor Modulator ◽  
Receptor Modulator

scholarly journals A Selective Androgen Receptor Modulator Enhances Male-Directed Sexual Preference, Proceptive Behavior, and Lordosis Behavior in Sexually Experienced, But Not Sexually Naive, Female Rats

Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2659-2668 ◽  
Author(s):  
A. E. Kudwa ◽  
F. J. López ◽  
R. F. McGivern ◽  
R. J. Handa
Keyword(s):  
Androgen Receptor ◽  
Sexual Desire ◽  
Bone Growth ◽  
Sexual Experience ◽  
Estradiol Benzoate ◽  
Sexual Preference ◽  
Female Rats ◽  
Selective Androgen Receptor Modulator ◽  
Receptor Modulator ◽  
Selective Ligand

Androgens influence many aspects of reproductive behavior, including sexual preference of females for males. In oophorectomized women with sexual desire disorder, testosterone patches improve libido, but their use is limited because of adverse side effects. Selective androgen receptor modulators offer an improved safety profile for both sexes: enhancing libido and muscle and bone growth in a manner similar to steroidal androgens but with fewer adverse effects, such as hirsutism, acne, and prostate growth. The current study investigated the action of a novel selective androgen receptor modulator (LGD-3303 [9-chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3H-pyrrolo-[3,2-f]quinolin-7(6H)-one]) on male-directed sexual preference, proceptivity, and lordosis behavior of female rats. LGD-3303 is a nonsteroidal, nonaromatizable, highly selective ligand for the androgen receptor and effectively crosses the blood-brain barrier. Gonadectomized female rats were treated with LGD-3303 (3–30 mg/kg) or vehicle by daily oral gavage. Results showed that LGD-3303 treatment enhanced sexual preference of females for males but only if females had previous sexual experience. This occurred after 1 or 7 d of treatment. In contrast, preference for males was inhibited by LGD-3303 treatments of sexually naive females. The LGD-3303 increase in male preference was blocked by pretreatment with the androgen receptor antagonist flutamide. LGD-3303 treatment increased lordosis and proceptivity behaviors in ovariectomized females primed with suboptimal doses of estradiol benzoate plus progesterone. These data support the concept that LGD-3303 can stimulate aspects of female sexual behavior and may serve as a potential therapeutic for women with sexual desire disorders.

scholarly journals Combination Treatment With a Selective Androgen Receptor Modulator q(SARM) and a Bisphosphonate Has Additive Effects in Osteopenic Female Rats*

2009 ◽  
Vol 24 (2) ◽  
pp. 231-240 ◽  
Author(s):  
Eric G Vajda ◽  
Aimee Hogue ◽  
Kimberly N Griffiths ◽  
William Y Chang ◽  
Kelven Burnett ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Combination Treatment ◽  
Female Rats ◽  
Additive Effects ◽  
Selective Androgen Receptor Modulator ◽  
Receptor Modulator
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