Androgen Receptor Expression in the Levator Ani Muscle of Male Mice

Abstract

The spinal nucleus of the bulbocavernosus (SNB) is a sexually dimorphic group of motoneurones that innervates the bulbocavernosus (BC) and levator ani (LA), skeletal muscles that attach to the base of the penis. In many species, including mice, rats and hamsters, the LA and BC have been found to be highly responsive to androgen and, in rats, these muscles mediate several effects of androgen on the SNB system. However, characterising the SNB system in mice is important because of the availability of genetic models in this species. In the present study, we examined AR expression in skeletal muscles of C57/BlJ6 adult male mice using immunoblotting and immunocytochemistry, comparing the BC/LA to the androgen-unresponsive extensor digitorum longus (EDL). We found similar differences in AR expression for these muscles in the mouse as previously reported for rats. In mice, the BC/LA contains more AR protein than does the EDL. At the cellular level, the LA contains a higher percentage of AR positive myonuclei and fibroblasts than does the EDL. Finally, AR expression is enriched at the neuromuscular junction of mouse LA fibres. The increased expression of AR in the LA compared to the EDL in both muscle fibres and fibroblasts indicates that each cell type may critically mediate androgen action on the SNB system in mice.

Myocytic androgen receptor controls the strength but not the mass of limb muscles

“…4). Differential responses in perineal and leg muscles might result from a higher number of AR-expressing myonuclei in perineal than in limb muscles (29) or from cell-specific transcriptional activities of AR in these muscles.…”

“…Two natural steroids, testosterone and dihydrotestosterone, bind and activate AR to regulate target gene expression. Because AR is expressed in various cell types of skeletal muscle in mammals (e.g., fibroblasts, satellite cells, and myofibers) (29)(30)(31), as well as in motoneurons (31), all these cells are potential sites of androgen action. In addition, androgens might act through poorly characterized nongenomic pathways (32) or after aromatization by activation of estrogen receptors (33).…”

Molecular Changes at the Post-Synapse and Improved Motor Function Suggest Accelerated Recovery with SARM Treatment in an Androgen-Depleted Animal Model of Nerve Injury

“…One day prior to nerve crush, and for the remainder of study, mice were treated with either, 1) Vehicle (hydroxyethycellulose; HEC), 2) Testosterone propionate (TP; 14 mg/kg/wk), or 3) A selective androgen receptor modulator (SARM; 2 mg/kg/day). Specific perineal muscles in the body, such as the Bulbocavof sacrifice the perineal muscles (levator ani and bulbar cavernosus) were isolated as a positive control for a typical anabolic androgen response [21,22].…”

“…This functional deficit was maintained in all treatment groups until day 14, after which the groups began improving in a treatment dependent manner. At 21 days post-nerve crush, the SARM treated animals showed significantly greater functional capacity with increased latency for leg release in both the nerve crushed and contralateral leg when compared to the vehicle treated ernosus (BC) and the Levator Ani (LA), are particularly androgen sensitive and will significantly atrophy upon loss of androgen signaling (e.g., ORX setting), and hypertrophy in the presence of increased circulating androgen signaling [21,22]. These tissues provide a Pharmacodynamic (PD) marker for confirming the anabolic effects of TP and SARM treatments.…”

The biological and clinical advances of androgen receptor function in age-related diseases and cancer [Review]

“…Perineal skeletal muscles, which are bulbocavernosus (BC) and levator ani (LA), collectively BC/LA, are highly androgen sensitive in rodents [76]. Postnatal gonadal testosterone production in males increases BC/ LA muscle fiber number and muscle fiber hypertrophy at puberty.…”