Distribution of androstenedione and its effects on total free fatty acids in pregnant rats.
Androstenedione, an anabolic steroid used to enhance athletic performance, was administered in corn oil by gastric intubation once daily in the morning to nonpregnant female rats at a dose of 5 or 60 mg/kg/day, beginning two weeks before mating and continuing through gestation day (GD) 19. On GD 20, the distribution of androstenedione and other steroid metabolites was investigated in the maternal plasma and target organs, including brain and liver. The concentration of estradiol in plasma approached a statistically significant increase after treatment as compared with the controls, whereas the levels of androstenedione, testosterone and progesterone were not significantly different from the controls. In the liver, the concentrations of androstenedione and estradiol only were increased in a dose-related manner. None of these steroids was detectable in the brain. Androstenedione treatment also produced changes in the level of selected free fatty acids (FFAs) in the maternal blood, brain, liver and fetal brain. The concentrations of palmitic acid (16:0) and stearic acid (18:0) in the plasma were not significantly different between the controls and treated rats. However, oleic acid (18:1), linoleic acid (18:2) and docosahexaenoic acid (DHA, 22:6) were 17.94 +/- 2.06 microg/ml, 24.23 +/- 2.42 microg/ml and 4.08 +/- 0.53 microg/ml, respectively, in the controls, and none of these fatty acids was detectable in the treated plasma. On the other hand, palmitic, stearic, oleic, linoleic and DHA were present in both control and treated livers. Among the FFAs in liver, linoleic and DHA were increased 87% and 169%, respectively, over controls. Palmitic, stearic and oleic acids were not significantly affected by the 60 mg/kg treatment. These were present in both control maternal and fetal brains, whereas linoleic acid was found only in fetal brain control. DHA was present only in the control maternal brain (0.02 +/- 0.02 microg/mg protein) and fetal brain (0.24 +/- 0.15 microg/mg protein). The results indicated that androstenedione exhibits significantly different effects on the FFA composition among target organs during pregnancy.
Kim
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US FDA, Center for Food Safety and Applied Nutrition, Office of Applied Research and Safety Assessment, Laurel, MD 20708, USA. chung.kim@fda.hhs.gov
Ross
I A
IA
Sprando
R L
RL
Johnson
W D
WD
Sahu
S C
SC
Flynn
T J
TJ
Wiesenfeld
P L
PL
Collins
T F X
TF
O'Neilll
R K
RK
Sapienza
P
P
D045930:Anabolic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D000735:Androstenedione / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism; D008041:Linoleic Acids / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D051381:Rats; D014018:Tissue Distribution
D045930:Anabolic Agents; D005230:Fatty Acids, Nonesterified; D008041:Linoleic Acids; D000735:Androstenedione; D004958:Estradiol