Differential response of oxidative and glycolytic skeletal muscle fibers to mesterolone

Hasan A Asfour,Bright Starling Emerald,Mohammed Z Allouh,Ayman G Mustafa,Emad I Shaqoura,Raed S Said

doi:10.1038/s41598-021-91854-4

Abstract

Oxidative and glycolytic muscle fibers differ in their ultrastructure, metabolism, and responses to physiological stimuli and pathological insults. We examined whether these fibers respond differentially to exogenous anabolic androgenic steroids (AASs) by comparing morphological and histological changes between the oxidative anterior latissimus dorsi (ALD) and glycolytic pectoralis major (PM) fibers in adult avian muscles. Adult female White Leghorn chickens (Gallus gallus) were randomly divided into five groups: a vehicle control and four mesterolone treatment groups (4, 8, 12, and 16 mg/kg). Mesterolone was administered orally every three days for four weeks. Immunocytochemical techniques and morphometric analyses were employed to measure the changes in muscle weight, fiber size, satellite cell (SC) composition, and number of myonuclei. Mesterolone increased both body and muscle weights and induced hypertrophy in glycolytic PM fibers but not in oxidative ALD fibers. Mesterolone induced SC proliferation in both muscles; however, the myonuclear accretion was noticeable only in the PM muscle. In both muscles, the collective changes maintained a constant myonuclear domain size and the changes were dose independent. In conclusion, mesterolone induced distinct dose-independent effects in avian oxidative and glycolytic skeletal muscle fibers; these findings might be clinically valuable in the treatment of age-related sarcopenia.

Highlights

From other AASs by its unique chemical structure that does not undergo ring aromatization into estrogen it has no estrogenic side effects
We found that oral administration of mesterolone significantly increases the number of SCs in maturing avian pectoralis, a response accompanied by increased myonuclear density and DNA c ontent[12]
There were no significant differences in the mean cross-sectional area (CSA) and fiber diameter between the anterior latissimus dorsi (ALD) muscle fibers of control and mesterolone-treated groups or among the mesterolone-treated groups (Table 1)

Summary

Introduction

From other AASs by its unique chemical structure that does not undergo ring aromatization into estrogen it has no estrogenic side effects. Mesterolone has a very low hepatotoxicity, and confers oral activity that allows its oral route of administration[14] These advantages of mesterolone encourage it to be considered as a potential alternative therapy for age-related sarcopenia instead of injectable AASs. A previous study reported that mesterolone significantly increases the weight and fiber size of the soleus muscle of transgenic m ice[15]. We found that oral administration of mesterolone significantly increases the number of SCs in maturing avian pectoralis, a response accompanied by increased myonuclear density and DNA c ontent[12]. It is unclear if mesterolone has distinct effects on different types of normal adult muscle fibers. We hypothesized that mesterolone differentially influences these two muscles by inducing distinct changes in their fiber morphometric and cellular characteristics

Methods

Results

Conclusion