Research Update #6

by Hypertrophy

As we approach the new millennium we find the science of building muscle progressing faster than ever before. Long gone are the days of simple trial and error when it comes to building muscle. The modern bodybuilder demands more than just "hear say" if they are to adopt a new training routine or nutritional supplement. This column was created to keep today’s bodybuilder on the cutting edge of scientific research that might benefit them in their quest for body perfection.

Some call it cruelty to animals, some call it science, I call it Research Update! Our primate friends [not to be confused with our acromegalic, GH abusing, homosapien friends] have stepped up to the plate to ensure new drugs are safe and ready for human consumption. Our hats go off to them in this months Research Update.

Shooting blanks? It may be the Tamoxifen.

Title: Effect of chronic administration of Tamoxifen on fertility in male bonnet monkeys (Macaca radiata).

Researchers: Rao AJ, Ramachandra SG, Ramesh V, Krishnamurthy HN, Jayaraman S, Gopalakrishnan K, Juneja HS

Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.

Source: Andrologia 1998 May-Jun;30(3):129-32

Summary: Administration of Tamoxifen via the Alzet pump at a rate of 50 micrograms hr-1 for 90 days in the adult male bonnet monkeys Macaca radiata had no effect on the serum testosterone concentration determined at 10 AM and 10 PM as well as total sperm count determined at 15-day intervals over a period of 260 days. However, a significant reduction in sperm motility was observed beyond 90 days up until the 225th day. Breeding studies conducted from day 90 to 260 revealed that these males were infertile.

Discussion: Tamoxifen, or Nolvadex, is classified as an antiestrogen. I’m sure most of you are already familiar with this drug. It works as an antiestrogen by competitively binding to estrogen receptors. Although it has high affinity for estrogen receptors it has little if any estrogenic effects in most tissues. It is used by bodybuilders to prevent or treat gynecomastia and water retention. The interesting thing about this study was the fact that Tamoxifen, an antiestrogen, made the male monkeys infertile. This is in agreement with another recent study looking at the effects of an aromatase inhibitor (Steroids 1998 Jul-Aug;63(7-8):414-20) on fertility also in male monkeys. Both of these studies point to an important role of estrogen in male fertility. Tamoxifen, unlike the aromatase inhibitor which caused a 2-10 fold increase in serum testosterone levels, showed no effect on serum testosterone. The effect on spermatogenesis was clearly due to estrogen. Their sperm count was fairly normal, however, the sperm couldn’t swim to save their own lives. The take home message is that if you want to start a family between shows, stay away from Nolvadex and Proviron. On the other hand, these two compounds may be potential male birth control remedies. I guess the glass is either half full or half empty depending on how you look at it.

Protein is key to holding on to precious gains!

Title: Myofibrillar protein catabolism is rapidly suppressed following protein feeding

Researchers: Nagasawa T, Hirano J, Yoshizawa F, Nishizawa N Department of Bioscience and Technology, Faculty of Agriculture, Iwate University, Japan.

Source: Biosci Biotechnol Biochem 1998 Oct;62(10):1932-7

Summary: The immediate response of protein degradation to food intake and the factors for its regulation in rat skeletal muscle were examined. The concentration of N tau-methylhistidine (MeHis) in serum and the rates of MeHis release from isolated soleus and extensor digitorum longus muscles were reduced in the period from 3 to 6 h after refeeding, indicating that the rate of myofibrillar protein degradation in the rat decreased immediately after refeeding. Changes in the serum concentration of insulin and corticosterone were not synchronized with those in the myofibrillar protein degradation. When rats were fed on a protein-free diet, no reduction of serum MeHis concentration or of the rate of MeHis release from isolated muscles after refeeding was apparent. Furthermore, there was a tendency toward suppressing myofibrillar protein degradation with a higher protein content of the diet. These results suggest that the suppression of myofibrillar protein degradation by food intake was regulated by dietary proteins.

Discussion: People have been debating the need of dietary protein in athlete’s diets for decades. You usually have two camps, those who say bodybuilders "might" need a little extra protein, and those who claim that massive quantities of protein are best. This study backs up the claims that protein is critical to preserving muscle. Science is finally telling us what we already new from trial and error. If you recall from December’s Research Update (Mesomorphosis Volume 1, Number 9), there are crucial initiation factors, that control protein synthesis, which are sensitive to the availability of amino acids within the muscle. These initiation factors are bound to binding proteins rendering them inactive until free amino acids are available. You may have all the right hormones present, but if you don’t have free amino acids present at the same time you will not get muscle growth. You may be able to hold on to muscle with hormones alone, but you will not have a net gain in muscle without all the players present together including hormones, macronutrients, and autocrine growth factors.

New fix for hair loss: They call it RU58841, I call it Miracle Grow!

Title: Evaluation of RU58841 as an anti-androgen in prostate PC3 cells and a topical anti-alopecia agent in the bald scalp of stumptailed macaques.

Researchers: Pan HJ, Wilding G, Uno H, Inui S, Goldsmith L, Messing E, Chang C Department of Pathology, University of Rochester Medical Center, NY 14642, USA.

Source: Endocrine 1998 Aug;9(1):39-43

Summary: The effect of androgen receptor transcriptional activation by RU58841, a nonsteroidal anti-androgen, was studied in the human prostate cancer PC3 cell line by cotransfection with wild-type androgen receptor (wt AR) and an androgen-responsive reporter (MMTV-ARE-CAT) construct. Anti-androgens, hydroxyflutamide [Eulexin], and bicalutamide [Casodex], and the antiestrogen, genistein, were studied in parallel for comparison with RU58841. The wt AR was activated only by the androgen dihydrotestosterone (DHT). Neither the anti-androgens nor antiestrogen can enhance AR transcriptional activity at 10(-11)-10(-7)M in PC3 cells. Hydroxyflutamide, RU58841, and Casodex, but not genistein, displayed competitively suppressive effects on DHT activation of wt AR. The potency of RU58841 was comparable to that of hydroxyflutamide. From this result, topical application of RU58841, which is considered to be a potential therapy for skin diseases, may induce systemic side effects. However, RU58841, on topical application, revealed a potent increase in density, thickening, and length of hair in the macaque model of androgenetic alopecia, whereas no systemic effects were detected. Together our results suggest that RU58841 may have potent antagonism to the wt AR and could be considered as a topically applied active anti-androgen for the treatment of androgen-dependent skin disorders, such as acne, androgenetic alopecia, and hirsutism.

Discussion: RU58841 is ready to kill two birds with one stone. Not only does it save your hair during those once in a life time cycles, it can also prevent acne. Now, Finasteride (Propecia,Proscar) can also do this to some extent, but it is taken internally and has systemic effects. RU58841 can be applied topically and, in this study, was shown not to have any systemic affects. In fact, RU58841 has been used on humans,...sort of (Br J Dermatol 1997 Nov;137(5):699-702). In the study just referred to, scalp was cut off the head of balding men and grafted onto female nude mice taking test propionate. Now that’s what I call science! Anyway, RU58841 was then applied to the scalp sewn onto the mice. The results were very positive with significant hair growth as well as the induction of repeated growth cycles. RU58841 has also been shown to significantly prevent acne when applied topically. You may be wondering when RU58841 will become available. I wish I could say for sure. Right now all that I know for sure is that it is looking like the most promising drug to treat both balding and acne simply by rubbing it on where you need it. Convenience and ease of use with no unwanted side effects, what more could you ask for? Keep your eye out for this one!