Modulation of the cytosolic androgen receptor in striated muscle by sex steroids

Naomi E Rance, S. R. Max

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

We studied the influence of orchiectomy (GDX) and steroid administration on the level of cytosolic androgen receptor in rat levator ani muscle and rat skeletal muscles (tibialis anterior and extensor digitorum longus). Androgen receptor binding to muscle cytosol was measured using [3H]methyltrienolone (R1881) as ligand, a 100-fold molar excess of unlabeled R1881 to assess nonspecific binding, and a 500-fold molar excess of triamcinolone acetonide to prevent binding to glucocorticoid and progestin receptors. Bound and free ligand were separated by column chromatography with Sephadex G-75. In levator ani muscles from intact animals (controls), maximum R1881 binding (B(max)), determined by Scatchard analysis, was 2.5 fmol/mg protein (K(d) = 0.68 nM). Thirty days after GDX, B(max) increased to 500% of the control value, with no significant change in K(d) (0.96 nM). Using saturating levels of R1881, B(max) was increased to 280% of the control value 12 h post-GDX, 600% at 14 days, 478% at 30 days, and 133% at 44 days. The increase in receptor binding was blocked by cycloheximide. Administration of Silastic capsules containing testosterone propionate 30 days post-GDX resulted in R1881 binding at the control level at 44 days. Surprisingly, administration of 17β-estradiol (E2) 30 days post-GDX resulted in increased (480%) R1881 binding. Thus, E2 may cause induction of the cytosolic androgen receptor in levator ani muscle from GDX rats; alternatively, the rate of receptor degradation may be altered. R1881 binding by skeletal muscle cytosol was increased 139% at 12 h, 212% on day 14, 220% on day 30, and 158% on day 44 with respect to the control value. Administration of testosterone propionate at 30 days caused R1881 binding to return to the control value by day 44, whereas E2 was without influence. The differences in response of levator ani and skeletal muscle receptors may account for the differential effects of sex steroids on these muscle types.

Original languageEnglish (US)
Pages (from-to)862-866
Number of pages5
JournalEndocrinology
Volume115
Issue number3
StatePublished - 1984
Externally publishedYes

Fingerprint

Metribolone
Striated Muscle
Androgen Receptors
Steroids
Anal Canal
Muscles
Testosterone Propionate
Skeletal Muscle
Cytosol
Ligands
Triamcinolone Acetonide
Orchiectomy
Glucocorticoid Receptors
Progesterone Receptors
Cycloheximide
Capsules
Chromatography
Estradiol

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Modulation of the cytosolic androgen receptor in striated muscle by sex steroids. / Rance, Naomi E; Max, S. R.

In: Endocrinology, Vol. 115, No. 3, 1984, p. 862-866.

Research output: Contribution to journalArticle

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abstract = "We studied the influence of orchiectomy (GDX) and steroid administration on the level of cytosolic androgen receptor in rat levator ani muscle and rat skeletal muscles (tibialis anterior and extensor digitorum longus). Androgen receptor binding to muscle cytosol was measured using [3H]methyltrienolone (R1881) as ligand, a 100-fold molar excess of unlabeled R1881 to assess nonspecific binding, and a 500-fold molar excess of triamcinolone acetonide to prevent binding to glucocorticoid and progestin receptors. Bound and free ligand were separated by column chromatography with Sephadex G-75. In levator ani muscles from intact animals (controls), maximum R1881 binding (B(max)), determined by Scatchard analysis, was 2.5 fmol/mg protein (K(d) = 0.68 nM). Thirty days after GDX, B(max) increased to 500{\%} of the control value, with no significant change in K(d) (0.96 nM). Using saturating levels of R1881, B(max) was increased to 280{\%} of the control value 12 h post-GDX, 600{\%} at 14 days, 478{\%} at 30 days, and 133{\%} at 44 days. The increase in receptor binding was blocked by cycloheximide. Administration of Silastic capsules containing testosterone propionate 30 days post-GDX resulted in R1881 binding at the control level at 44 days. Surprisingly, administration of 17β-estradiol (E2) 30 days post-GDX resulted in increased (480{\%}) R1881 binding. Thus, E2 may cause induction of the cytosolic androgen receptor in levator ani muscle from GDX rats; alternatively, the rate of receptor degradation may be altered. R1881 binding by skeletal muscle cytosol was increased 139{\%} at 12 h, 212{\%} on day 14, 220{\%} on day 30, and 158{\%} on day 44 with respect to the control value. Administration of testosterone propionate at 30 days caused R1881 binding to return to the control value by day 44, whereas E2 was without influence. The differences in response of levator ani and skeletal muscle receptors may account for the differential effects of sex steroids on these muscle types.",
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