Abstract
The temporal nature of estrogenic suppression of Leydig cell testosterone production was investigated. Adult rats were injected SC with 50 micrograms/100 g BW of DES or vehicle. Animals were sacrificed at 4, 8, or 12 h following a single injection or at 12 h following the latter of two daily injections for 1 or 2 days. Collagenase-dispersed interstitial cells were obtained, and population I and II Leydig cells were subsequently isolated on metrizamide gradients. Population I and II Leydig cells produced in vitro testosterone levels of 7.19 +/- 0.86 and 12.84 +/- 1.86 ng/10(6) cells/3 h, respectively. These levels were increased to 10- to 13-fold in the presence of hCG of dbcAMP. No significant difference was noted in the responsiveness of these two populations to the in vitro additions. DES administration in vivo for 8-48 h resulted in dramatic and significant decreases in basal and stimulated testosterone production in vitro in both populations. However, DES treatment for 4 h was relatively ineffective in blocking testosterone production in vitro. The inhibitory patterns exhibited by the two populations differed considerably. Population I displayed a uniform degree of inhibition throughout the treatment, whereas population II exhibited a more transient suppression by estrogen. Thus, population II appeared to be less sensitive to the estrogenic effects than population I at 48, 24, and 12 h of treatment. These data indicate that both population I and population II Leydig cells become sensitive to the inhibitory effects of estrogens between 4 and 8 h of in vivo treatment and suggest that certain differences exist between the two populations with respect to the temporal action of estrogens.
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