High-density lipoprotein response to 5-alpha-dihydrotestosterone and testosterone in Macaca fascicularis: a hormone-responsive primate model for the study of atherosclerosis.
A decrease in high-density lipoprotein cholesterol (HDL-C), a major risk factor for coronary artery disease, occurs during puberty in males. Previous studies have shown this decrease with testosterone (T) therapy for adolescent males, but the mechanism of this effect is unknown and has not been studied in a non-human primate. Two adult male monkeys (Macaca fascicularis) were studied to determine simultaneous changes in plasma androgens and HDL-C during the phases precastration (Ci); postcastration (Cx); Cx and T therapy; Cx and dihydrotestosterone (DHT) therapy; and T and 5-alpha-reductase inhibitor therapy (4-MA). After castration, the HDL-C concentrations increased significantly in both animals (monkey A, 57.0 +/- 1.8 mg/dL SE to 66.6 +/- 2.2, P less than .005; monkey B, 62.9 +/- 1.6 to 80.2 +/- 1.7, P less than .001). T-propionate treatment produced a significant decrease in HDL-C (monkey A, 48.0 +/- 5.0, P less than .01; monkey B, 43.5 +/- 0.5, P less than .001), which was similar to HDL-C reductions seen when treated with a nonaromatizeable androgen, DHT-propionate (monkey A, 47.5 +/- 1.5, P less than .005; monkey B, 44.5 +/- 3.5, P less than .001). T and the 5-alpha-reductase inhibitor therapy did not increase HDL-C from the levels with T therapy alone (monkey A, 55.7 +/- 1.9, NS; monkey B, 57.3 +/- 0.3, NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Greger
N G
NG
Department of Pediatrics, Baylor College of Medicine, Houston, TX.
Insull
W
W
Probstfield
J L
JL
Keenan
B S
BS
D058891:5-alpha Reductase Inhibitors; D000731:Androstanes / Q000494:pharmacology; D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control*; D001378:Azasteroids / Q000494:pharmacology; D008076:Cholesterol, HDL / Q000097:blood*; D013196:Dihydrotestosterone / Q000097:blood / Q000494:pharmacology*; D004195:Disease Models, Animal; D008075:Lipoproteins, HDL / Q000097:blood*; D008252:Macaca fascicularis; D008297:Male; D009919:Orchiectomy; D013739:Testosterone / Q000097:blood / Q000494:pharmacology*
D058891:5-alpha Reductase Inhibitors; D000731:Androstanes; D001378:Azasteroids; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D013196:Dihydrotestosterone; C051710:L 636028; D013739:Testosterone