Clomiphene citrate potentiates the adverse effects of estrogen on rat testis and down regulates the expression of steroidogenic enzyme genes

The effects of clomiphene citrate on testicular function and steroidogenic enzyme gene expression were investigated in rats estrogenized with estradiol-3-benzoate.

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Authors

Shilpa Bharti, M.Sc., M.M. Misro, Ph.D., Umesh Rai, Ph.D.

Volume 99, Issue 1, Pages 140-148.e5, January 2013

Abstract

Objective:

To investigate the antiestrogenic effect of clomiphene citrate (CC) in male rats estrogenized with estradiol-3-benzoate (EB).

Design:

Prospective experimental study.

Setting:

Laboratory.

Animals:

Adult male albino rats (Holtzman strain).

Intervention(s):

CC was given alone or in combination with EB.

Main Outcome Measure(s):

Testicular function and steroidogenic enzyme gene expression were evaluated in control versus treated groups.

Result(s):

EB after 30 days of treatment induced a rise in TUNEL-positive germ cells adversely affecting spermatogenesis with complete absence of elongated spermatids or sperms. CC alone had only a moderate effect. In contrast, CC+EB synergistically inflicted more adverse effects as apoptotic germ cells per tubule rose further. Significant down-regulation in expression of testicular steroidogenic enzyme genes StAR, p450scc, 3β-HSD, and p450c17 was observed. In the EB-alone group, aromatase gene expression in the testis was up-regulated but reversed in brain and liver tissues. CC alone had little modulatory effect on aromatase expression. On the other hand, CC+EB countered the EB-induced rise of aromatase expression in the testis.

Conclusion(s):

The above findings indicate that CC in the presence of estrogen synergistically potentiates more adverse effects in testis, inhibiting expression of upstream steroidogenic enzyme genes and leading to disruption of steroidogenesis.

Read the full text at: http://www.fertstert.org/article/S0015-0282(12)02138-3/fulltext


Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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