Disparate effect of Clomiphene and tamoxifen on pituitary gonadotropin release in vitro
E. Y. Adashi, A. J. Hsueh, T. H. Bambino and S. S. Yen
The direct effects of Clomiphene citrate (Clomid), tamoxifen, and estradiol (E2) on the gonadotropin-releasing hormone (GnRH)-stimulated release of luteinizing hormone (lh - leutenizing hormone - ) and follicle-stimulating hormone (FSH - follicle stimulating hormone - ) were studied in cultured anterior pituitary cells obtained from adult ovariectomized rats. Treatment of pituitary cells with Clomid or enclomid (10(-8) M) in vitro for 2 days resulted in a marked sensitization of the gonadotroph to GnRH as reflected by a 6.5-fold decrease in the ED50 of GnRH in terms of lh - leutenizing hormone - release from 2.2 x 10(-9) M in untreated cells to 3.6 x 10(-10) M. Treatment with E2 or Clomid also increased the sensitivity of the gonadotroph to GnRH in terms of FSH - follicle stimulating hormone - release by 4.3- and 3.3-fold respectively. Tamoxifen, a related antiestrogen, comparable to Clomid in terms of its ability to compete with E2 for pituitary estrogen receptors, was without effect on the GnRH-stimulated lh - leutenizing hormone - release at a concentration of 10(-7) M. Furthermore, tamoxifen, unlike Clomid, caused an apparent but not statistically significant inhibition of the sensitizing effect of E2 on the GnRH-stimulated release of lh - leutenizing hormone - . Our findings suggest that Clomid and its Enclomid isomer, unlike tamoxifen, exert a direct estrogenic rather than an antiestrogenic effect on cultured pituitary cells by enhancing the GnRH-stimulated release of gonadotropin.
In Summary: These tests involved infusing patients with 100mcg of GnRH and measuring the output of pituitary lh - leutenizing hormone - in response. The focus of this test is to see how sensitive the pituitary is to Gonadotropin Releasing Hormone. The more sensitive the pituitary, the more lh - leutenizing hormone - will be released. The tests showed that after ten days of treatment with Nolvadex , pituitary sensitivity to GnRH increased slightly compared to pre-treated values. This is contrast to 10 days of treatment with 150mg Clomid, which was shown to consistently DECREASE pituitary sensitivity to GnRH (more lh - leutenizing hormone - was released before treatment). As the study with Nolvadex progresses to 6 weeks, pituitary sensitivity to GnRH was significantly higher than pre-treated or 10-day levels. At this point the same 20mg dosage was also raising testosterone and lh - leutenizing hormone - levels to an average of 183% and 172% of base values, respectively, which again is measurably higher than what was noted 10 days into therapy. Within 10 days of treatment Clomid is already exerting an effect that is causing the pituitary to become slightly desensitized to GnRH, while prolonged use of Nolvadex serves only to increase pituitary sensitivity to this hormone. That is not to say Clomid won't increase testosterone if taken for the same 6 week time period. Quite the opposite is true. But we are, however, noticing an advantage in Nolvadex.