The effects of sex hormone binding globulin (SHBG) on testosterone transport into the cerebrospinal fluid.
The movement of testosterone (T) from blood across the blood-brain barrier (BBB) is thought to reflect the combined effects of T's lipid solubility and the presence of circulating binding proteins for T such as albumin or sex hormone binding globulin (SHBG). Since the adult rat lacks a circulating specific high affinity sex steroid binding protein, examination of the disappearance from serum and uptake into cerebrospinal fluid (CSF) of [3H]T before and after SHBG or albumin infusion should provide insight into the function of these two proteins with respect T transport. Three groups of adult male Sprague-Dawley rats were cannulated at the femoral vein and cisterna magna. In a control group (n = 8), [3H]T was given as an intravenous bolus beginning at time zero; multiple serum and CSF collections were assayed for counts per min (cpm) during the subsequent 45 min. Data from these animals were then compared to those seen in animals that received either purified human SHBG (hSHBG) (n = 7) or human albumin (hALB) (n = 6) 10 min prior to the [3H]T infusion. High performance liquid chromatography was used to monitor the metabolic fate of the steroid infusate at the end of each study period. Infusion of hSHBG increased serum concentrations from undetectable to 93.8 nM/l (mean +/- SEM, n = 6). Administration of hALB significantly increased (25.0 +/- 1.2 g/l at baseline, 33.4 +/- 1.6 g/l post-infusion, mean +/- SEM, P less than 0.03, n = 5) the circulating albumin concentration. Comparison of data from each group of animals demonstrated that (1) following an i.v. injection of radiolabeled T, the initial decline in serum [3H]T was significantly reduced (P less than 0.03) in the presence of hSHBG, (2) hALB did not affect the movement of [3H]T out of serum, (3) the time to peak appearance of [3H]T in the CSF was significantly delayed (P less than 0.02) by the presence of circulating hSHBG, and (4) the net quantity of [3H]T found in the cSF under steady-state conditions was not affected by serum SHBG or albumin levels. This study demonstrates that high-affinity steroid binding proteins do modulate the transport of sex steroids across the BBB. Specifically, SHBG delays the clearance of T from serum and slows the rate of T uptake into the CSF during non-equilibrium conditions.(ABSTRACT TRUNCATED AT 400 WORDS)
Hobbs
C J
CJ
Department of Medicine, Madigan Army Medical Center, Tacoma, Washington.
Jones
R E
RE
Plymate
S R
SR
D000704:Analysis of Variance; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000502:physiology; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000502:physiology; D012738:Sex Hormone-Binding Globulin / Q000502:physiology*; D013739:Testosterone / Q000134:cerebrospinal fluid* / Q000378:metabolism
D012709:Serum Albumin; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone