Reduction of testosterone availability to 5 alpha-reductase by human sex hormone-binding globulin in the rat ventral prostate gland in vivo.
The present studies assess the effects of human sex hormone-binding globulin (SHBG) on the conversion of [3H]testosterone (T) into dihydrotestosterone (DHT) in rat ventral prostate gland in vivo using a constant aortic infusion technique. The DHT/T ratio was determined using two-dimensional thin-layer chromatography (TLC), and these results were confirmed with reverse-phase high-performance liquid chromatography. The prostatic gland DHT/T ratio was 2.1 +/- 0.4, 1.3 +/- 0.2, 0.24 +/- 0.02, or 1.1 +/- 0.2, following a 60 sec aortic perfusion of [3H]testosterone dissolved in either Krebs-Henselite buffer (KHB), 5 g/dl human serum albumin (HSA), human pregnancy serum (HPS), or heat inactivated HPS, respectively. Heat inactivation (60 degrees C, 60 min) selectively denatured SHBG in HPS. The distribution of [3H]testosterone in rat ventral prostate was examined with thaw-mount light in microscopic autoradiography. Following an aortic perfusion of [3H]testosterone in buffer alone, the radiolabeled steroid was uniformly distributed among the epithelial and stromal compartments. However, the [3H]steroid hormone was selectively sequestered in the stromal compartment following aortic perfusion of HPS. In conclusion, these studies demonstrate that human SHBG markedly restricts the availability of circulating testosterone to 5 alpha-reductase in the prostate gland in vivo and that the presence of SHBG in serum causes the selective sequestration of the steroid hormone within the stromal compartment of the gland in vivo.
Ellison
S A
SA
Department of Medicine, UCLA School of Medicine 90024-1682.
Pardridge
W M
WM
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D000818:Animals; D001011:Aorta; D001345:Autoradiography; D002855:Chromatography, Thin Layer; D013196:Dihydrotestosterone / Q000378:metabolism; D008297:Male; D010477:Perfusion; D011467:Prostate / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D012738:Sex Hormone-Binding Globulin / Q000008:administration & dosage / Q000378:metabolism* / Q000502:physiology; D013739:Testosterone / Q000008:administration & dosage / Q000378:metabolism*
D012738:Sex Hormone-Binding Globulin; D013196:Dihydrotestosterone; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase