Regulation of the Androgen and Glucocorticoid Receptors in Rat and Mouse Skeletal Muscle Cytosol*

Abstract

Using a charcoal technique, we determined the relative binding affinity of some anabolic compounds for the androgen and glucocorticoid receptors in cytosol from rat skeletal muscle. Only a few of the compounds analyzed competed for the receptor-binding sites. The androgen and glucocorticoid receptors were analyzed in rat and mouse skeletal muscle cytosols by Scatchard analysis. In rats grouped according to sex and age, the cytosolic protein content was about the same in all groups, but the DNA content decreased with increased weight of the animal regardless of sex (male, female, or castrated male). The glucocorticoid receptor did not differ in concentration (2-3 pmol/g tissue) or ligand affinity (Kd, 10-40 nM) among the groups, but the androgen receptor concentration decreased with increased weight and age of the animals, more in the case of males than in the case of females or castrates. The Kd for the androgen receptor increased with age in males but was constantly about 0.2 nM for castrates or females. In adult intact rats, the androgen and glucocorticoid receptor concentrations in muscle cytosol from females were about 100 and 3000 fmol/g tissue, respectively, the corresponding values for males being about 50 and 2000 fmol/g tissue, respectively. Short term castration or adrenalectomy increased the concentration of and ligand affinity for the androgen and glucocorticoid receptors, respectively. After long term castration of male rats, the concentration of both receptors increased during 5 weeks to about the female level, only to decrease later. Neonatally castrated male rats had about the same androgen receptor concentrations and Kd values as female rats. Female mice had higher androgen receptor concentrations (approximately 700 fmol/g tissue) than rats. Intact male mice had about 200 fmol androgen receptor-binding sites/g tissue, and the same amount was found in mice bearing the testicular feminization (Tfm) mutant gene. In summary, the concentrations of androgen and glucocorticoid receptors in rat skeletal muscle are regulated at least by the testes. The presence of androgen receptors in skeletal muscle from Tfm mice is surprising and may motivate a reinvestigation of the regulation of androgen receptors in Tfm animals.

Effects of nandrolone decanoate on respiratory and peripheral muscles in male and female rats

“…In the present study, only the weight of the gastrocnemius failed to do so, and, moreover, it changed gender dependently. A graded response of different muscles to androgen admin istration was previously reported as being the result of differences in the level of androgen-binding receptors within the muscle cytosol (3,6). Different anabolic effects in males compared with females were observed in young animals (7,10,22).…”

“…The exact mechanisms for this gender-dependent anabolic effect is not known and is beyond the aim of the present investigation. The intrinsic difference in the basal level of circulating endogenic androgens may play a role because it is higher in sexually normal male animals compared with females and seems to result in a smaller number of androgen-binding sites on the muscle cytosol (6). Fur thermore, surpassing the physiological level of andro gens in males has been reported to result in 1 ) depres sion of the natural production of testosterone (25), 2) downregulation of androgen-binding receptors (23), 3) decrease in appetite (16), and 4) a metabolic conversion to excess estradiol (15).…”

Anabolic steroids in sport: biochemical, clinical and analytical perspectives

“…28 A possible biochemical explanation of this clearly apparent di¡erence in response between sexes may be drawn from studies with rodents. Dahlberg et al 41 showed that the fully developed intact male rat had a lower concentration of androgen receptors compared to the fully developed female rat. Castration increased the ligand a¤nity of these receptors.…”

Androgen and Glucocorticoid Receptor Heterodimer Formation

“…1). Several mammalian tissues coexpress the receptors for these two hormones, and in a number of these tissues they have opposing effects (2)(3)(4)(5)(6)(7)(8)(9). For example, the androgens act through the androgen receptor (AR) 1 to stimulate protein synthesis in skeletal muscle and to increase smooth muscle and prostate proliferation.…”

“…For example, the androgens act through the androgen receptor (AR) 1 to stimulate protein synthesis in skeletal muscle and to increase smooth muscle and prostate proliferation. Additionally, androgen receptors may be involved directly or indirectly in triggering aggressive dominant male behavior (2,5,7). In contrast, glucocorticoids act through the glucocorticoid receptor (GR) to cause skeletal muscle protein degradation and to inhibit smooth muscle and prostate proliferation and are correlated with submissive behavior in male rats (2,5,6,8,9).…”