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Myogenic Regulatory Factors, Oh My!

MRFs are involved in muscle hypertrophy as well as fiber-composition changes.

You must be thinking, another one of those geeky columns from Doc Antonio, with him pontificating about the nuances of muscle physiology. Well, indeed, the verdict is in, and I am guilty of reading about some of the most obscure muscle physiology science around. I want to translate this esoteric and bizarre stuff for you so that you can impress your friends at the gym with terms like myogenin, MyoD, Myf5 or, my favorite, herculin (also known as MRF4).

A primer on MRFs (myogenic regulatory factors). What are the MRFs? First, let’s get the names straight: myogenin, MyoD (pronounced my-oh-dee), Myf5 (pronounced mif-five) and MRF4 (pronounced mirf-four or just MRF4, a.k.a. herculin). Let’s look at a couple of studies in which the MRFs are ‘turned on,’ and it’ll be as clear as a goldfish bowl why they’re so important. In fact, I suspect that in the future, scientists will look for natural ways to kick-start the MRFs in the hope of producing bigger, faster and stronger athletes.

Lift weights and elevate the MRFs. A Danish study used six men (24 years old and an average 183 pounds) who were ‘physically active’ but did not necessarily do regular weight training.1 They performed an exercise regimen of two sets of six to eight reps and two more sets of 10 to 14 reps on a leg press and leg extension machine. So they did a total of eight sets. Subjects were told to lift the concentric, or positive, part of the lift as quickly as possible while doing the eccentric, or negative, portion slowly. They took a 90-second rest between sets and a three-minute rest between the two exercises.

The researchers took muscle biopsies 1 1/2 hours before exercise and then immediately afterward, and one, two, six, 24 and 48 hours after exercise. So what did they find?

Myogenin, MyoD and MRF4 messenger RNA (mRNA) concentration increased by 100 to 400 percent from 0 to 24 hours after exercise. Why is that important? Because the MRFs are involved in muscle hypertrophy as well as fiber-composition changes vis-‘-vis resistance training. The next question is whether there’s an ideal method of training to increase MRFs. Can nutrition further elevate them?

Dr. Darryn Willoughby of Texas Christian University examined the effects of weight training plus creatine supplementation on MRFs.2 He looked at how MRFs were affected by both weight training alone and weight training plus creatine supplementation. He divided 22 untrained men into three groups: control, placebo and creatine. The creatine and placebo groups trained three times per week using three sets of six to nine reps at 85 to 90 percent of their 1RMs on the leg press, leg extension and leg curl exercises. The creatine group got six grams per day of creatine during the 12-week study, and the placebo group received a similar-looking placebo.

What happened to the MRFs? MyoD protein and RNA expression increased more in the placebo and creatine groups than in the control group, but the researchers found no differences between the placebo and creatine groups. Myogenin and MRF4 mRNA and protein expression were greater in the creatine group than in the placebo group. And their expression in the placebo group was greater than in the control group. The results showed no differences for Myf5.

In summary, you could say that weight training alone will jack up myogenin, MRF4 and MyoD but not Myf5. When you add creatine to the mix, you get a further elevation of MRF4 and myogenin. According to the study’s authors, ‘Increases in myogenin and MRF4 mRNA and protein may play a role in increasing myosin heavy chain expression, already shown to occur with creatine supplementation.’ What that means is this: If you bust your ass in the gym and hit the weights hard, you turn on certain genes that affect muscle growth. If you also take creatine, you’ll further turn on those genes. The bottom line is that exercise and creatine supplementation do alter gene expression.

More work needs to be done to identify the best training protocol for turning on MRFs and to see whether other nutrients similarly affect MRFs.


1 Psilander, N., et al. (2003). Resistance exercise alters MRF and IGF-1 mRNA content in human skeletal muscle. J Appl Physiol. 95:1038-1044.
2 Willoughby, D., and Rosene, J.M. (2003). Effects of oral creatine and resistance training on myogenic regulatory factor expression. Med Sci Sports Exerc. 35:923-9.

Editor’s note: Jose Antonio, Ph.D., CSCS, earned his doctorate at the University of Texas Southwestern Medical Center. He is a co-editor (with Jeffrey R. Stout, Ph.D.) of and contributor to Sports Supplements (Lippincott Williams & Wilkins), Sports Supplement Encyclopedia (Nutricia), Supplements for Strength-Power Athletes (Human Kinetics) and Supplements for Endurance Athletes (Human Kinetics). For more information click your way to IM

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