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J. Biol. Chem., Vol. 276, Issue 3, 2153-2158, January 19, 2001
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From the Oregon Regional Primate Research Center and Department of
Physiology and Pharmacology, Oregon Health Sciences University,
Beaverton, Oregon 97006
Gonadotropin-releasing hormone (GnRH) regulates
pituitary gonadotropin release and is a therapeutic target for human
and animal reproductive diseases. In the present study we have utilized
the technique of fluorescence resonance energy transfer to
monitor the rate of GnRH receptor-receptor interactions. This technique relies on the observation that the degree of physical intimacy of
molecules can be assessed by the tendency of proximal fluorophores to
exchange energy. Our data indicate that GnRH agonist, but not antagonist, occupancy of the GnRH receptor promotes physical intimacy (microaggregation) between receptors. The time course indicates that
this occurs promptly (<1 min) after occupancy and persists for at
least 80 min and within the physiologically relevant range of the
releasing hormone. The process measured is not inhibited by 0.1 mM vinblastin, 2 µM cytochalasin D, or
3 mM EGTA, an observation that distinguishes it from
macroaggregation (patching, capping, and internalization).
These observations, along with reports from other laboratories, are
consonant with a growing body of evidence that indicates that
microaggregation is an early event following agonist occupancy of the
receptor and part of the mechanism by which effector regulation occurs.
Gonadotropin-releasing Hormone Receptor Microaggregation
RATE MONITORED BY FLUORESCENCE RESONANCE ENERGY TRANSFER*
*
This work was supported by Grants HD19899, HD18185, and
RR00163 from the National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence and requests for reprints should be
addressed: 505 NW 185th Ave., Beaverton, OR 97006. Tel.: 503-690-5297; Fax: 503-690-5569; E-mail: connm@ohsu.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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