Pharmacokinetics of oral dehydroepiandrosterone (DHEA) in the ovariectomised cynomolgus monkey.
Humans and primates are unique in having adrenals that secrete large amounts of DHEA and DHEA-S in the circulation. These steroids act as precursors of active androgens and estrogen's in a long series of peripheral target intracrine tissues. The marked decline of serum DHEA and DHEA-S concentrations with age in men and women has been incriminated in the development of various pathologies. This study provides detailed information on the effect of a single 50mg oral dose of DHEA on circulating estrogen's as well as androgens and their metabolites over 10h in adult ovariectomised (OVX) Cynomolgus monkeys. Serum DHEA, DHEA-S, testosterone (Testo) and androstenedione (4-dione) concentrations increased rapidly with a maximal value at approximately 1h after DHEA administration followed by a 60-80% decrease during the next 2-6h. An important sulfatation of DHEA occurs through first hepatic pass, thus, leading to a marked increase in serum DHEA-S. Serum androst-5-ene-3beta,17beta-diol and androsterone glucuronide (ADT-G) levels remained elevated on a plateau for 6h. Androstan-3alpha,17beta-diol-glucuronide, estradiol and estrone levels remained unchanged. The present data indicate the predominant transformation of the adrenal precursor DHEA into active androgens in peripheral tissues and support the importance of measurement of circulating glucuronide derivatives as index of peripheral or intracrine androgen formation and action.
Laboratory of Molecular Endocrinology and Oncology, Laval University Medical Center (CHUL), Laval University, Que., Canada.
Mathias
M
Leblanc
Claude
C
Labrie
Alain
A
Bélanger
Bernard
B
Candas
Fernand
F
Labrie
D000284:Administration, Oral; D000735:Androstenedione / Q000097:blood; D000818:Animals; D003687:Dehydroepiandrosterone / Q000097:blood / Q000493:pharmacokinetics*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005260:Female; D008252:Macaca fascicularis; D010052:Ovariectomy; D010919:Placebos; D013739:Testosterone / Q000097:blood
D010919:Placebos; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate