Main Research Findings for LGD 3303 

 

1. Increases muscle mass without negatively affecting weight of the prostate in orchidectomized, male Sprague-Dawley rats. 

 

2. Increases bone mineral content (BMC) and BMD in ovariectomized, female Sprague-Dawley rats.

 

Selected Data

 

1. Male Sprague-Dawley rats, approximately 7-8 weeks old, weighing ~200 grams, were purchased from Harlan for experimental testing. The subjects were stored in cages containing 2-3 rats each, and were categorized by weight into groups of 5. The rats were anesthetized and either orchidectomized (ODX) or given a sham surgery. The research team left the rats for 14 days in order to ensure sufficient atrophy in the muscles and the prostate as a result of hypogonadism. 

 

After the 14 day waiting period, the rats were administered varying doses of either LGD 3303 or testosterone propionate. LGD was subcutaneously injected in a suspension of Tween-80, polyethylene, glycol-400, and 0.1% carboxymethyl cellulose in water, once daily. The ratio was 0.005% to 10% to 89.995%, respectively. After two weeks of treatment the rats were euthanized so the researchers were able to measure weight of the prostate and the levator ani muscle [1].

 

2. Female Sprague-Dawley rats, approximately 3 months old, weighing 175-200 grams, were purchased from Harlan for experimental testing. Test subjects were stored in cages containing 2-3 rats each, and were then categorized into groups to receive an ovariectomy (OVX) or a sham surgery. The rats were left alone for 7 weeks in order for osteopenia to develop. 

 

After 7 weeks the rats were split into treatment groups: Sham + vehicle, OVX + vehicle, OVX + LGD-3303, OVX + alendronate, and OVX + LGD-33033, + alendronate. The subjects were administered their treatment method via oral savage; administration occurred daily over 12 weeks. After 12 weeks the rats were euthanized and the weight of the gastrocnemius muscle and inguinal fat pad were taken. The bones of the subjects were harvested for DXA scans, biomechanical testing, and histomorphology in order to examine the elicited changes in BMD, BMC, and muscle mass [1]. 

 

Discussion 

 

1. Results of the study found that both administration of LGD-3303 and testosterone propionate were able to promote anabolic activity in ODX male rats. In a dose-dependent manner the weight of the levator ani muscle significantly improved. While both compounds promote muscle growth, testosterone propionate also increases the weight of the prostate gland at a similar rate as the muscles. LGD-3303 on the other hand increased weight of the muscle without drastic prostate growth. A 1 mg/kg dose of testosterone propionate was found to stimulate the ventral prostate to 50% of eugonadal levels. A 1 mg/kg dose of LGD-3303 was shown to have negligible effects on the ventral prostate, while higher doses (3 mg/kg and above) only stimulated the ventral prostate to <50% of eugonadal levels. 

Figure 1. Changes in prostate weight in response to administration with either testosterone propionate or LGD-3303

 

2. After treating the female rats with LGD-3303 or LFD-3303 + alendronate, it was found that body and organ weight in OVX female rats were significantly increased. Both treatment groups experienced an increase in gastrocnemius weight and a decrease in inguinal fat pad weight.

Figure 2.  Changes in body weight, muscle weight, and fat pad weight in response to different treatment variables. 

 

DXA scans reported that LGD-3303 elicited positive effects on BMC and BMD in cortical and cancellous bone. However, in combination treatment both bone mineral density and bone mineral content increased in the lumbar spine more than treatment with LGD 3303 alone. 

 

In the histomorphoectomy studies it was found that LGD 3303 treatment increased periosteal bone formation at the midfemoral diaphysis. This is important to note considering that the midfemoral diaphysis is not a site of osteoclast remodeling, This indicates that any changes to the bone are through activation of osteoblast and suggests effective anabolic activity. 

 

The biomechanical studies reported that all three treatments improved peak loading midfemur. However, the combination treatment was more successful than either single treatment but the difference was not significant. All three treatments also increased peak compressive load of the lumbar spine. Again, the combination treatment was more successful than either single treatment, however, the combination treatment was not significantly more effective than LGD-3303. 

Figure 3: Changes in BMC and BMD in response to different treatment variables.

 

Conclusion 

**LAB USE ONLY**

*This information is for educational purposes only and does not constitute medical advice. THE PRODUCTS DESCRIBED HEREIN ARE FOR RESEARCH USE ONLY. All clinical research must be conducted with oversight from the appropriate Institutional Review Board (IRB). All preclinical research must be conducted with oversight from the appropriate Institutional Animal Care and Use Committee (IACUC) following the guidelines of the Animal Welfare Act (AWA).

 

Citations 

[1] Vadja EG, Hogue A, Griffith KN, Chang WY, Burnett K, Chen Y, Marschke K, Mais DE, Pedram B, Shen Y, Oeveren A, Zhi L, Lopez FJ, Meglasson MD. “Combination Treatment With a Selective Androgen Receptor Modulator (SARM) and a Bisphosphonate Has Additive Effects in Osteopenic Female Rats*.” Journal of Bone and Mineral Research, vol. 4, no. 3, 2009. American Society for Bone and Mineral Research, https://asbmr.onlinelibrary.wiley.com/doi/pdf/10.1359/jbmr.081007.

LGD-3303 SARM is sold for laboratory research use only. Terms of sale apply. Not for human consumption, nor medical, veterinary, or household uses. Please familiarize yourself with our Terms & Conditions prior to ordering.