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Endocrinology, Vol 109, 1122-1126, Copyright © 1981 by Endocrine Society

ARTICLES

Inhibition of gonadotropin-releasing hormone-stimulated luteinizing hormone release by pimozide: evidence for a site of action after calcium mobilization

PM Conn, DC Rogers and T Sheffield

In the present work, we show that pimozide is a noncompetitive antagonist of gonadotropin-releasing hormone (GnRH)-stimulated LH release from pituitary cell cultures. For several other neurotropic agents, the concentration needed to inhibit 50% of LH release in response to GnRH correlates well with the ability to inhibit enzyme activation by calmodulin in vitro. Pimozide does not alter the affinity or amount of releasing hormone binding by the GnRH receptor. The additional observation that pimozide inhibits Ca2+ ionophore (A23187 and ionomycin)-stimulated LH release suggests that the locus of pimozide action is after Ca2+ mobilization. Pimozide is known to bind and inactivate the Ca2+-calmodulin complex, and as Ca2+ is a second messenger for GnRH, it is possible that calmodulin is the target of pimozide in this system.


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M. C. H. Holland, S. Hassin, and Y. Zohar
Effects of Long-Term Testosterone, Gonadotropin-Releasing Hormone Agonist, and Pimozide Treatments on Gonadotropin II Levels and Ovarian Development in Juvenile Female Striped Bass (Morone saxatilis)
Biol Reprod, November 1, 1998; 59(5): 1153 - 1162.
[Abstract] [Full Text]


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