AJP - Endocrinology and Metabolism, Vol 257, Issue 6 E937-E942, Copyright © 1989 by American Physiological Society
Nonesterified fatty acids modulate steroidogenesis in mouse Leydig cells
A. W. Meikle, S. J. Benson, X. H. Liu, W. D. Boam and J. D. Stringham
Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City 84132.
The effects of nonesterified fatty acids (NEFA) in modulating testosterone
synthesis stimulated by luteinizing hormone (LH, 10 ng/sample) were
investigated in isolated adult mouse Leydig cells. LH-stimulated
testosterone production was inhibited by triglycerides (0-500 mg/dl, 50
mg/dl, 94% of the control and 500 mg/dl, 40%) and by a mixture of NEFA (100
microM, 70% of control, 200 microM, 54%, and greater than 200 microM, less
than 50%). Oleic acid was a more potent inhibitor than linoleic, stearic,
or palmitic acids. 8-Bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP, 5
mM) stimulated testosterone production comparable to LH but failed to
reverse the inhibition of steroidogenesis produced by the NEFA. The
inhibition produced by NEFA was dependent on extracellular Ca2+; and a Ca2+
channel antagonist, verapamil (10 microM), enhanced the inhibition of
chylomicrons and fatty acids. 22(R)-hydroxycholesterol (10 microM) reversed
the inhibition produced by NEFA. The inhibitory effects of NEFA were
reversible by removal of the fatty acids. The results indicate that NEFA
are potent modulators of testosterone synthesis in Leydig cells stimulated
with either LH, cAMP, or intracellular Ca2+. NEFA inhibit steroidogenesis
at one of the steps preceding conversion of cholesterol to pregnenolone.
