Main Research Findings

1. The study conducted by researchers Piu et. Al concluded that AC 262,536 is a potent SARM that acts an agonist to androgen receptors and elicits similar anabolic effects as testosterone without the adverse side effects of prostate and seminal vesicle growth.

2. In addition to the positive anabolic benefits, AC 262,536 was found to regulate pituitary functioning. The compound is capable of lowering LH without the negative androgenic effects elicited by testosterone.

Selected Data

1. Male Sprauge-Dawley rats ranging in weight from 200-225 grams were anesthetized and either surgically castrated or subject to a sham-operation. After the surgery the animals were given 5 days to recover and assimilate to their environment before undergoing experimental treatment. The castrated animals were then given either a placebo, 1 mg/kg of testosterone propionate (TP), or varying doses of 3,10, and 30 mg/kg of AC 262,536. The treatments were injected subcutaneously over the course of 14 days and the animals were euthanized 24 hours after the last injection.

In order to identify any changes that may have occurred in the three experimental groups, the researchers obtained plasma samples and harvested specific organs. This study primarily focused on weight fluctuations of the prostate, seminal vesicles, and levator ani muscle. These three organs were removed and dissected away from any excess tissue and blotted dry in order to accurately assess their weight [1].

2. As a result of orchidectomy in rats, levels of luteinizing hormone (LH) tend to elevate. Typically the LH spike is treated with testosterone supplementation. In addition to measuring the weight of the prostate, seminal vesicles, and levator ani muscle, the research group of Piu et. Al also tracked LH levels in the mice administered AC 262,536. The mice were administered either a vehicle, a 1 mg/kg dose of TP, or doses of AC 262,536 varying from 3, 10, and 30 mg/kg. Plasma levels of LH were measured and recorded using an ELISA kit [1].

Discussion

1. Overall, the research team concluded that A 262,536 elicited anabolic effects similar to those of TP without many of the negative androgenic side effects. Results of the study reported that after 14 days of treatment with TP there was a dramatic increase in prostate growth. While the prostate was measured to be 23 ± 3 mg in vehicle treated animals, the prostate of rats treated with TP were weighed in at 223 ± 14 mg. That being said, the rats that were administered AC 262,536 experienced very little prostate growth. For the subjects given the 3 mg/kg dose, average prostate weight was 12 ± 2 mg. The measured prostate weight of the 10 mg/kg and 30 mg/kg dosage groups slightly increased to 55 ± 6 mg and 54 ± 5 mg, respectively.

Similar patterns were seen in seminal vesicle growth; there was a 14-fold increase in weight compared to the vehicle group from 52 ± 5 mg to 748 ± 48 mg. AC 262,536 only slightly elevated seminal vesicle weight. The 3 mg/kg dose increased the weight to 67 ± 4 mg, while the 10 mg/kg and 30 mg/kg doses were measured at 150 ± 12 mg and 208 ± 15 mg, respectively.

Figure 1: Changes in prostate and seminal vesicle weight based on different experimental treatments.

The anabolic effects of AC 262,536 and TP were compared by weighing the levator ani muscle of the mice. The levator ani muscle in test subjects administered AC 262,536 was restored to approximately 70% of the maximum effect seen in the subjects administered TP. In addition to the strong anabolic effects, as the previously mentioned results reported, there were minimal adverse androgenic effects associated with AC 262,536. That being said, AC 262,536 was confirmed as an agonist of androgen receptors [1].

2. Results of this study found that AC 262,536 reduced LH levels to a greater extent than TP in a dose-dependent manner. In comparison to the vehicle, TP led to a drastic decrease in LH levels, measured at 3.12 ± 0.69 ng/ml vs. 9.95 ± 0.60 ng/ml, respectively. Initially, the 3 mg/kg dose of Ac 262,536 reduced levels of LH by approximately 40% of TP’s maximum effect. However, the 10 mg/kg and 30 mg/kg dose of AC 262,536 led to a greater decrease in LH levels than TP. The 10 mg/kg dose led to a 1.53 ± 0.34 ng/ml decrease in plasma LH levels, while the 30 mg/kg led to a 3.12 ± 0.69 ng/ml. That being said, when compared to TP, AC 262,536 elicits a greater reduction in LH levels after castration without the significant androgenic side effects. Further analysis was conducted in order to determine the dose needed in order to reach 50% of the displayed effects of TP. The ED50 reported this dose to be 2.8 mg/kg of AC 262,356 [1].

Figure 2: Changes in plasma LH levels based on different experimental treatments.

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] Piu F, Gardell LR, Son T, Schlienger N, Lund BW, Schiffer HH, Vanover KE, Davis RE, Olsson R, Bradley SR. Pharmacological characterization of AC-262536, a novel selective androgen receptor modulator. J Steroid Biochem Mol Biol. 2008 Mar;109(1-2):129-37. doi: 10.1016/j.jsbmb.2007.11.001. Epub 2007 Nov 22. PMID: 18164613.

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