Androgen metabolism by human peritoneal macrophages.
Peritoneal macrophages (PM) were obtained by peritoneal dialysis from a regularly menstruating woman with renal failure. Macrophages (10(6) cells) were incubated at 37 degrees C for various periods of time (0-4 hr) in the presence of 14C-androstenedione or 3H-androstenedione and various concentrations (0.06-5.06 microM) of nonradiolabeled androstenedione (A). Testosterone (T) formed was purified by column chromatography, thin layer chromatography, acetylation, and recrystalization to constant 3H:14C ratios. The rate of formation of T from A was linear for nearly 2 hr. Conversion of A to T was linear at cell numbers in the incubation up to 1 x 10(6). The formation of T from A followed Michaelis-Menten kinetics at concentrations of A between 0.06 and 5.06 microM. The apparent Km of the enzyme for A was 0.75 microM and the Vmax for T formation from A in these cells was 33.9 pmol x hr-1 x 10(6) cells-1. PM were obtained also from normal patients (n = 6) and patients with endometriosis (n = 5). The rate of T synthesis from A in PM obtained from patients with endometriosis [527 +/- 263 pmol x hr-1 x 10(6) cells-1 (mean +/- SEM, n = 5)] was similar to that observed in PM obtained from normal patients [518 +/- 226 pmol x hr-1 x 10(6) cells-1 (mean +/- SEM, n = 6)]. We observed a near 30-fold variation in the rate of formation of T from A by PM obtained from different individuals (range 54 to 1580 pmol x hr-1 x 10(6) cells-1). Further study is needed to elucidate the physiologic significance of PM androgen metabolism and its relationship to reproductive function.
Coddington
C C
CC
Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
Letterie
G S
GS
Klein
T A
TA
Winkel
C A
CA
D000328:Adult; D000735:Androstenedione / Q000378:metabolism*; D002452:Cell Count; D002478:Cells, Cultured; D004715:Endometriosis / Q000378:metabolism / Q000628:therapy; D005260:Female; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008597:Menstrual Cycle; D010529:Peritoneal Cavity / Q000378:metabolism*; D010530:Peritoneal Dialysis; D013739:Testosterone / Q000096:biosynthesis / Q000302:isolation & purification; D013997:Time Factors
D013739:Testosterone; D000735:Androstenedione