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PLASMA LIPOPROTEIN PROFILE OF THE MALE CYNOMOLGUS MONKEY UNDER PHYSIOLOGICAL, HYPOGONADAL AND COMBINED ANDROGEN BLOCKADE CONDITIONS
M Leblanc, MC Bélanger, P Julien, C Bélanger, A Tchernof, A Bélanger, C Labrie, F Labrie
Quebec, Quebec
Normal testosterone and adrenal serum steroid levels are associated with a favorable lipoprotein profile in men. It has also been reported that orchiectomy (GDX) results in an atherogenic lipid profile while combined androgen blockade (CAB) induces a favorable lipid profile in men with prostatic carcinoma. To assess the opposite effects of GDX and CAB on lipid metabolism, we compared changes in plasma lipoproteins, mesenteric fat metabolism as well as serum and intratissular sex steroid concentrations over 3 months in INTACT, GDX and GDX+FLUTAMIDE (FLU) male cynomolgus monkeys.
Serum concentrations of DHEA, DHEA-S and androstenediol remained stable. Serum androstenedione (–40%), Testosterone (–97%), DHT (–87%) and ADT-G (–75%) levels decreased in both GDX groups while 3
(–85%), estradiol (-50%) and ADT-G (–50%) concentrations also decreased after GDX. Orchiectomy induced an significant increase in plasma total cholesterol (TC) (+40%), LDL-C (+78%) and LDL-apoB (+58%). In the GDX+FLU group, TC and LDL-C remained stable while LDL-apoB showed a tendency to decrease. Mesenteric fat lipolytic or lipogenic activities could not explain these differences in the lipid profile.
In conclusion, orchiectomy and CAB result in opposite effects on the lipid profile which might be explained by androgen deprivation and/or possible residual estrogenic effects derived from adrenal precursors. By abolishing the activity of DHT at the androgen receptor, FLU might in fact favor the estrogenic effect in tissues of the GDX+FLU group. These data support the notion of an important regulatory effect of androgens and estrogens produced from adrenal precursors in peripheral intracrine tissues in the monkey.
DNC
Canadian Institutes of Health Research