Biol Reprod Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by CLARK, J. H.
Right arrow Articles by GUTHRIE, S. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by CLARK, J. H.
Right arrow Articles by GUTHRIE, S. C.
Agricola
Right arrow Articles by CLARK, J. H.
Right arrow Articles by GUTHRIE, S. C.

Biology of Reproduction, Vol 25, 667-672, Copyright © 1981 by Society for the Study of Reproduction

Agonistic and Antagonistic Effects of Clomiphene Citrate and Its Isomers

JAMES H. CLARK 1, and SYLVIA C. GUTHRIE 1

1 Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030


The agonistic and antagonistic properties of clomiphene citrate (CL) and its isomers were examined in the rat uterus. Immature rats (21 days old) were injected with various doses of estradiol benzoate (EB), CL, zuclomiphene (ZUC, cis isomer), and enclomiphene (ENC, trans isomer), and uterine weight or epithelial cell height was measured. EB treatment produced a typical dose-response curve for uterine weight with a steep slope, while the curves resulting from treatment with CL, ZUC, or ENC were attenuated with a very shallow slope. These differences in shapes of the dose-response curves render the determination of relative potency estimates inaccurate and misleading. In contrast, the shapes of the dose-response curves for epithelial cell hypertrophy were similar for all four compounds. EB was more potent than any form of clomiphene; however, the maximum extent of cellular hypertrophy was not as great. The half maximal dose for each compound was EB, 0.35 ± 0.04 µg; ENC, 25.0 ± 2.0 µg; CL, 35.0 ± 3.1 µg; and ZUC, 65.0 ± 7.1 µg. The ability of these drugs to antagonize the action of EB was examined by injecting EB plus CL, ZUC, or ENC and measuring the uterine weight or epithelial cell hypertrophy 72 h later. All three forms of the drug were antagonistic to EB-induced uterine weight gain over the same dose ranges in which they were agonistic by themselves. No antagonistic effects were observed on estradiol stimulation of epithelial cell hypertrophy.

These data show that CL and its isomers are fully capable of stimulating epithelial cell hypertrophy in the rat uterus, and thus, valid relative potency estimates can be obtained with this response. This is not true when uterine weight gain is used because differential cell stimulation is not taken into account. In addition, CL and its isomers are agonistic and antagonistic over the same dose ranges when uterine weight gain is used; however, no antagonism of estrogen-stimulated cellular hypertrophy is measured. Therefore, broad generalizations concerning the estrogenicity or anti-estrogenicity of these compounds are not warranted and can be made only when specific end-points are evaluated.

Note:
ACKNOWLEDGMENTS We wish to thank Joni Lewis for the editing and typing of the manuscript, and Dr. J. O. Johnston for providing us with the various forms of clomiphene.

Submitted on April 23, 1981
Accepted on June 3, 1981




This article has been cited by other articles:


Home page
 Endocr. Rev.Home page
N. S. Macklon, R. L. Stouffer, L. C. Giudice, and B. C. J. M. Fauser
The Science behind 25 Years of Ovarian Stimulation for in Vitro Fertilization
Endocr. Rev., April 1, 2006; 27(2): 170 - 207.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1981 by the Society for the Study of Reproduction.