Effects of the Antiestrogen CI‐628 on Leydig Cell Function

The objective of this study was to use antiestrogens as probes into the relationship between 17β‐estradiol, the estrogen receptor, and Leydig cell steroidogenesis. Leydig cells purified by Metrizamide density gradient centrifugation were shown to contain estrogen receptors. Competitive inhibition studies performed in vitro demonstrated that the antiestrogens, CI‐628, tamoxifen, and enclomiphene, were effective competitors of [3H]‐estradiol binding with half‐maximal inhibition values of 10.8, 35, and 41 nM, respectively. Additionally, CI‐628 was shown to elicit depletion and Inhibit replenishment of the cytoplasmic estrogen receptor In vitro following a 50‐μg intraperitoneal injection. The effect of 10−6 M Cl‐628 on human chorionic gonadotropin (hCG)‐stlmulated testosterone production in purified Leydig cell incubations was assessed. The CI‐628 elicited a significant inhibition of hCG‐stimulated testosterone synthesle at time points from 1 to 3 hours while basal (unstimulated) synthesis was unaffected. These studies demonstrate an interaction between CI‐628 and the Leydig cell estrogen receptor. Furthermore, CI‐628 was shown to have a rapid inhibitory effect on hCG‐stimulated testosterone production in Leydig cells.