DEMONSTRATION OF A SPECIFIC ANDROGEN RECEPTOR IN RAT-HEART MUSCLE - RELATIONSHIP BETWEEN BINDING, METABOLISM, AND TISSUE LEVELS OF ANDROGENS

Binding, metabolism, and tissue levels of [3H]5α-androgens were investigated in rat heart muscle. [3H]Testosterone (T) and [3H]5α-dihydrotestosterone (5α-DHT) binding was analyzed in the 100, 000 × g cytosol by agargel electrophoresis. In vitro metabolism at 0C of T, 5α-DHT, and 5α-androstane-3α, 17β-diol (3α-diol) was investigated in the heart and skeletal muscle by thin layer chromatography. Endogenous T, 5α-DHT, and 3α-diol were extracted from the heart muscle, skeletal muscle, prostate, and plasma and quantified by RIA. The primary findings were the following. 1 A specific androgen receptor protein was demonstrated in the heart muscle cytosol which was physicochemically identical to the receptor protein described by us for various androgenic target organs. 2) The T binding displayed a dissociation constant (Kd) of 1.1 nM, and the maximal binding sites amounted to 2.0 fmol/mg cytosol protein. 3) The heart cytosol of prepuberal rats had the highest and the heart cytosol of uncastrated adult males had the lowest assayable receptor level. 4) The apparent order of steroid-receptor affinity was found to be: 17β- hydroxyestr-4-ene-3-one > T > 5α-DHT progesterone 6 - chloro -17 - hydroxy - lα, 2α - methy lene - 4, 6 - pregnadien- 3, 20-dione-17-acetate > 3α-diol > 17β-estradiol > 5α-androstane-3β, 17β-diol. Cortisol showed no affinity. The heart converted 5α-DHT at 0 C nearly completely to 5a-androstanediols, the 5α-DHT/5α-androstanediols ratio being 0.17 whereas the ratio for skeletal muscle was 2.7 (6). In heart muscle of uncastrated adult males T was accumulated, the average concentration being 3.0 ng/g tissue. The average T concentration in the prostate and skeletal muscle was 0.73 ng/g tissue and 1.3 ng/g tissue, respectively. The heart contains an androgen receptor and enzyme pattern which favor the accumulation of T instead of 5α-DHT. © 1978 by The Endocrine Society.