AJP - Endocrinology and Metabolism, Vol 240, Issue 2 125-E130, Copyright © 1981 by American Physiological Society
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) and follicle-stimulating hormone (FSH) 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 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 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 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. 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.
