TY - JOUR
T1 - Heart contains receptors for dihydrotestosterone but not testosterone
T2 - Possible role in the sex differential in coronary heart disease
AU - Sheridan, Peter J.
AU - McGill, Henry C.
AU - Aufdemorte, Thomas B.
AU - Triplett, Robert G.
AU - Holt, Richard G.
PY - 1989/4
Y1 - 1989/4
N2 - The sex differential in coronary heart disease is well documented but poorly understood. Previous studies have demonstrated receptors for dihydrotestosterone (DHT) in the myocardium and smooth muscle cells of arteries from a number of species. In this autoradiographic study, we further investigated and characterized the in vivo uptake and retention of the androgen binding in the male baboon. Adult castrated male baboons were injected with 1 μg/kg bw 3H‐testosterone; 1 hr after the injection, the animals were rapidly exsanguinated while under anesthesia. The heart and arterial system were removed and processed for autoradiography. As a negative control, one animal received both 3H‐testosterone and 100‐fold unlabeled testosterone. For positive controls, the pituitary gland, prostate, seminal vesicles, and other tissues were also removed and processed for autoradiography. In contrast to our previous finding with 3H‐DHT, no nuclear uptake and retention of 3H‐steroid was found in any of the cells in either the heart or the arterial system. In the positive control tissues, pituitary gland, prostate, seminal vesicles, and others, a very distinct nuclear uptake and retention of 3H‐steroid was observed, which was completely inhibited by the simultaneous injection of 100‐fold unlabeled testosterone. In the binding study, Scatchard analysis of the cytosol prepared from a 17‐year‐old female baboon demonstrated levels of androgen receptor (as determined by the use of radiolabeled R1881) comparable to that found in young adults. The results of these studies suggest that, in contrast to the generally accepted hypotheses, (1) circulating DHT, not testosterone, is the androgenic hormone that interacts with the cardiovascular tissue of the baboon and (2) there are separate receptors for testosterone and DHT in different tissues rather than a single receptor capable of binding both steroids.
AB - The sex differential in coronary heart disease is well documented but poorly understood. Previous studies have demonstrated receptors for dihydrotestosterone (DHT) in the myocardium and smooth muscle cells of arteries from a number of species. In this autoradiographic study, we further investigated and characterized the in vivo uptake and retention of the androgen binding in the male baboon. Adult castrated male baboons were injected with 1 μg/kg bw 3H‐testosterone; 1 hr after the injection, the animals were rapidly exsanguinated while under anesthesia. The heart and arterial system were removed and processed for autoradiography. As a negative control, one animal received both 3H‐testosterone and 100‐fold unlabeled testosterone. For positive controls, the pituitary gland, prostate, seminal vesicles, and other tissues were also removed and processed for autoradiography. In contrast to our previous finding with 3H‐DHT, no nuclear uptake and retention of 3H‐steroid was found in any of the cells in either the heart or the arterial system. In the positive control tissues, pituitary gland, prostate, seminal vesicles, and others, a very distinct nuclear uptake and retention of 3H‐steroid was observed, which was completely inhibited by the simultaneous injection of 100‐fold unlabeled testosterone. In the binding study, Scatchard analysis of the cytosol prepared from a 17‐year‐old female baboon demonstrated levels of androgen receptor (as determined by the use of radiolabeled R1881) comparable to that found in young adults. The results of these studies suggest that, in contrast to the generally accepted hypotheses, (1) circulating DHT, not testosterone, is the androgenic hormone that interacts with the cardiovascular tissue of the baboon and (2) there are separate receptors for testosterone and DHT in different tissues rather than a single receptor capable of binding both steroids.
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U2 - 10.1002/ar.1092230410
DO - 10.1002/ar.1092230410
M3 - Article
C2 - 2540679
AN - SCOPUS:0024537464
VL - 223
SP - 414
EP - 419
JO - Anatomical Record
JF - Anatomical Record
SN - 1552-4884
IS - 4
ER -