Biol Reprod Keystone Symposia Conference on Frontiers in Reproductive Biology & Regulation of Fertility.
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Biology of Reproduction, Vol 50, 363-367, Copyright © 1994 by Society for the Study of Reproduction

ARTICLES

Site of macrophage inhibition of luteinizing hormone-stimulated testosterone production by purified leydig cells

XR Sun and GP Risbridger
Institute of Reproduction and Development, Monash University, Clayton, Victoria, Australia.

It has been observed that testicular macrophages and testicular macrophage-conditioned medium reduce LH-stimulated, but not basal, testosterone production by purified Leydig cells in vitro. In order to determine how this inhibition occurs, we have examined the effects of testicular macrophages and testicular macrophage-conditioned medium at discrete stages of the steroidogenic pathway. The lesion in steroidogenesis is located at a step beyond cAMP formation, because the addition of dibutyryl cAMP or cholera toxin did not overcome the testicular macrophage-conditioned medium inhibition of LH-stimulated steroidogenesis by Leydig cells. This effect of testicular macrophage- conditioned medium on Leydig cell testosterone production is first observed at 18 h after initiation of culture. However, subsequent additions of 22R-hydroxycholesterol, pregnenolone, dehydroepiandrosterone, or androstenedione to the Leydig cell cultures can overcome the inhibition so that, after a further 6 h of incubation, testosterone production is not significantly different from that of control Leydig cells cultured in the absence of testicular macrophage- conditioned medium. These results suggest that the block in steroidogenesis is beyond cAMP production but prior to the formation of pregnenolone, dehydroepiandrosterone, and androstenedione. Since the medium for these cultures contained lipoprotein, it is possible that the testicular macrophage-conditioned medium metabolizes the lipoprotein, making it unavailable to the Leydig cells. However, our results show that preincubation of lipoprotein with testicular macrophage-conditioned medium does not significantly alter testosterone production by the Leydig cells in the culture. It is concluded that testicular macrophage-conditioned medium affects the transport or availability of cholesterol to mitochondria prior to further steps in the steroidogenic pathway.


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 EndocrinologyHome page
D. K. Pomerantz and V. Pitelka
Nitric Oxide Is a Mediator of the Inhibitory Effect of Activated Macrophages on Production of Androgen by the Leydig Cell of the Mouse
Endocrinology, March 1, 1998; 139(3): 922 - 931.
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Copyright © 1994 by the Society for the Study of Reproduction.