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Plasma Lipoprotein Profile in the Male Cynomolgus Monkey under Normal, Hypogonadal, and Combined Androgen Blockade Conditions

Molecular Endocrinology and Oncology Research Center (M.L., A.T., C.L., A.B., F.L.) and Lipid Research Center (M.-C.B., P.J., A.T.), Laval University Medical Center and Laval University, Québec, Canada, G1V 4G2

Address all correspondence and requests for reprints to: Pr. Fernand Labrie, Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, 2705 Laurier Boulevard, Québec, Québec, G1V 2G2, Canada. E-mail: fernand.labrie{at}crchul.ulaval.ca.

In men, orchiectomy (GDX) produces an atherogenic lipid profile, whereas combined androgen blockade (CAB) induces a favorable lipid pattern. To better understand the opposite effects of GDX and CAB on lipid metabolism, we have compared the changes in plasma lipoproteins, mesenteric fat metabolism, as well as serum and intratissular sex steroid concentrations in intact, GDX, and GDX+FLU [GDX male cynomolgus monkeys treated for 3 months with flutamide (FLU)].

Serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEA-S), and androstenediol remained stable after GDX. Serum androstenedione (–40%), testo (–97%), dihydrotestosterone (–89%), androsterone-glucuronide (–75%), and androstane-3,17ß-diol-glucuronide (–80%) levels decreased similarly in both GDX and GDX+FLU animals. Intratissular dihydrotestosterone (–59 to –99%), estradiol (–31 to –53%), and androsterone-glucuronide (–28 to –85%) concentrations also decreased after GDX. GDX induced significant increases in plasma low-density lipoprotein (LDL) (+78%) and high-density lipoprotein (+34%) cholesterol as well as in LDL-apoB (+58%) and high-density lipoprotein-apoAI (+32%). In the GDX+FLU group, except for the LDL-apoB that showed a tendency to decrease, lipid and apoprotein parameters remained unchanged compared with baseline values measured in intact animals. It is worth noting that these differences in the lipid profile could not be explained by changes in the metabolism of mesenteric adipose tissue.

In summary, in the cynomolgus monkey, GDX and CAB induced opposite effects on the plasma lipoprotein profile. These differences possibly result from differences in the specific activity of the androgens and estrogens derived from adrenal precursors. Such data support the suggestion that androgens and estrogens produced from adrenal precursors in peripheral intracrine tissues could have important, but so-far unsuspected, effects on the homeostasis of lipid and lipoprotein metabolism.

This work was supported by the Canadian Institutes of Health Research.

M.L. and M.-C.B. contributed equally to this work and should both be considered first authors.

Abbreviations: ADT-G, Androsterone-glucuronide; CAB, combined androgen blockade; CV, coefficient of variation; DEXA, dual-energy x-ray absorptiometry; DHEA, dehydroepiandrosterone; DHEA-S, dehydroepiandrosterone sulfate; DHT, dihydrotestosterone; 5-diol, androst-5-ene-3ß,17ß-diol; 3diol-G, androstane-3,17ß-diol-glucuronide; 4-dione, androstenedione; E₁, estrone; E₂, estradiol; FLU, flutamide; GC-MS, gas chromatography and negative chemical ionization mass spectrometry; GDX, orchiectomy; HDL-C, high-density lipoprotein cholesterol; INT, intact (group); LC-MS, HPLC and mass spectrometry; LDL-C, low-density lipoprotein cholesterol; LOQ, limit of quantification; ns, not significant; LPL, lipoprotein lipase; testo, testosterone; Tg, triglyceride(s); VLDL, very-low-density lipoprotein; WBFM, whole body fat mass; WBLM, whole body lean mass.

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