Dose dependent test and satellite cell proliferation

Very nice.

...so increased satellite cells = potentially new muscle fibers, correct? and if so they would be permanent.

correct. satellite cells means new muscle instead of just larger muscles.

jb

great,gui!

More food for thought.

From the Intro:

TESTOSTERONE SUPPLEMENTATION increases muscle mass in healthy hypogonadal men (7, 11, 25, 43, 48, 49), older men with low testosterone levels (26, 44, 45), and men with chronic illnesses and low testosterone levels (5, 8, 14). The anabolic effects of testosterone on muscle mass are dose and concentration dependent (9). Testosterone-induced increase in muscle mass is associated with a dose-dependent increase in cross-sectional areas of both type I and type II muscle fibers but is not attended by a change in muscle fiber number (40). However, the mechanisms by which testosterone increases muscle mass are not well understood (4). The prevalent dogma for the past 50 years has been that testosterone increases muscle mass by stimulating fractional muscle protein synthesis (11, 13, 28, 29, 37, 47, 52). Indeed, lowering of circulating testosterone concentrations by administration of a gonadotropin-releasing hormone (GnRH) agonist is associated with a reduction in fractional muscle protein synthesis (29); conversely, testosterone replacement in healthy hypogonadal men increases muscle protein synthesis (11). However, in a recent study (40), we noted that testosterone-induced muscle fiber hypertrophy is associated with a dose-dependent increase in myonuclear number. It would be difficult to explain this increase in myonuclear number if the sole effect of testosterone were on muscle protein synthesis. Muscle growth during postnatal development or hypertrophy is dependent on the addition of myonuclei to muscle fibers (1, 2, 30, 35, 36). Because the nuclei within the muscle fibers are postmitotic, new myonuclei must be contributed by the satellite cells that are outside the muscle fiber. Inhibition of satellite cell proliferation by gamma irradiation at doses that do not produce overt cellular damage prevents the muscle growth and increase in myonuclear number that follow muscle atrophy due to hindlimb Suspension(1). Muscle remodeling and repair following injury often involve satellite cell replication and recruitment of new stem cells into the myogenic cell lineage (35, 36). Similarly, the hypertrophy of levator ani muscle in the female rat induced by exogenous testosterone administration is associated with satellite cell entry into the cell cycle and proliferation (20�22, 31, 32, 46). Taken together, these animal data suggest that an increase in satellite cell number is an important antecedent of an increase in myonuclear number and muscle fiber adaptation leading to hypertrophy. However, we do not know whether similar changes in satellite cell number are also observed in testosterone-treated humans. Furthermore, previous reports studied satellite cells in the levator ani muscle of rodents, which differs significantly from skeletal muscle in the magnitude of response to castration and testosterone supplementation. Therefore, in this study, we tested the hypothesis that testosterone-induced muscle fiber hypertrophy would be associated with an increase in satellite cell number in the skeletal muscle of testosterone-treated men. Because the gains in muscle mass during testosterone supplementation are correlated with testosterone dose and concentrations (9), we hypothesized that the change in satellite cell number would also be correlated with testosterone dose and concentrations.
Accordingly, we measured the number of satellite cells in muscle biopsies obtained from healthy men in whom endogenous testosterone production was suppressed by administration of a GnRH agonist, and different levels of serum testosterone concentrations were created by weekly intramuscular injections of graded doses of Testosterone Enanthate. The design and the main findings of this study have been published (9, 40). Because significant increases in type I and type II muscle fiber cross-sectional areas were observed only in men receiving the 600-mg weekly doses of testosterone enanthate (40), and to a lesser extent in those receiving the 300-mg dose, we focused our analysis of satellite cells on these two groups. In addition, we included the 125-mg dose group as a control, because men in this group did not experience demonstrable muscle fiber hypertrophy or an increase in myonuclear number.

so much for the theory that low doses of test cause large muscle mass gains.

jb

J Clin Endocrinol Metab. 2004 Oct;89(10):5245-55.

Androgen receptor in human skeletal muscle and cultured muscle satellite cells: up-regulation by androgen treatment.

Sinha-Hikim I, Taylor WE, Gonzalez-Cadavid NF, Zheng W, Bhasin S.

Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California 90059, USA.

Androgens stimulate myogenesis, but we do not know what cell types within human skeletal muscle express the androgen receptor (AR) protein and are the target of androgen action. Because testosterone promotes the commitment of pluripotent, mesenchymal cells into myogenic lineage, we hypothesized that AR would be expressed in mesenchymal precursor cells in the skeletal muscle. AR expression was evaluated by immunohistochemical staining, confocal immunofluorescence, and immunoelectron microscopy in sections of vastus lateralis from healthy men before and after treatment with a supraphysiological dose of testosterone enanthate. Satellite cell cultures from human skeletal muscle were also tested for AR expression. AR protein was expressed predominantly in satellite cells, identified by their location outside sarcolemma and inside basal lamina, and by CD34 and C-met staining. Many myonuclei in muscle fibers also demonstrated AR immunostaining. Additionally, CD34+ stem cells in the interstitium, fibroblasts, and mast cells expressed AR immunoreactivity. AR expression was also observed in vascular endothelial and smooth muscle cells. Immunoelectron microscopy revealed aggregation of immunogold particles in nucleoli of satellite cells and myonuclei; testosterone treatment increased nucleolar AR density. In enriched cultures of human satellite cells, more than 95% of cells stained for CD34 and C-met, confirming their identity as satellite cells, and expressed AR protein. AR mRNA and protein expression in satellite cell cultures was confirmed by RT-PCR, reverse transcription and real-time PCR, sequencing of RT-PCR product, and Western blot analysis. Incubation of satellite cell cultures with supraphysiological testosterone and dihydrotestosterone concentrations (100 nm testosterone and 30 nm dihydrotestosterone) modestly increased AR protein levels. We conclude that AR is expressed in several cell types in human skeletal muscle, including satellite cells, fibroblasts, CD34+ precursor cells, vascular endothelial, smooth muscle cells, and mast cells. Satellite cells are the predominant site of AR expression. These observations support the hypothesis that androgens increase muscle mass in part by acting on several cell types to regulate the differentiation of mesenchymal precursor cells in the skeletal muscle.

SO short cycles probably also work that well?

I guess moderate cycles 500mg around 8-10 weeks are best?