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J. Biol. Chem., Vol. 277, Issue 48, 46391-46401, November 29, 2002
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From the Signalisation cellulaire, Régulation de gènes
et Physiologie de l'Axe gonadotrope, UMR CNRS 7079, Physiologie et
Physiopathologie, Université Pierre et Marie Curie,
75252 Paris Cedex 05, France
Nitric-oxide synthase type I (NOS I) is expressed
primarily in gonadotrophs and in folliculo-stellate cells of the
anterior pituitary. In gonadotrophs, the expression and the activity of NOS I are stimulated by gonadotropin-releasing hormone (GnRH) under
both experimental and physiological conditions. In the present study,
we show that pituitary adenylate cyclase-activating polypeptide (PACAP)
is twice as potent as GnRH at increasing NOS I levels in cultured rat
anterior pituitary cells. The action of PACAP is detectable after 4-6
h and maximal at 24 h, this effect is mimicked by 8-bromo-cAMP and
cholera toxin and suppressed by H89 suggesting a mediation through the
cAMP pathway. Surprisingly, NADPH diaphorase staining revealed that
these changes occurred in gonadotrophs exclusively although PACAP and
cAMP, in contrast to GnRH, have the potential to target several types
of pituitary cells including folliculo-stellate cells. There was no
measurable alteration in NOS I mRNA levels after cAMP or PACAP
induction. PACAP also stimulated cGMP synthesis, which was maximal
within 15 min and independent of cAMP, however, only part resulted from NOS I/soluble guanylate cyclase activation implying that in contrast to
GnRH, PACAP has a dual mechanism in cGMP production. Interestingly, induction of NOS I by PACAP markedly enhanced the capacity of gonadotrophs to produce cGMP in response to GnRH. The fact that PACAP
may act on gonadotrophs to alter NOS I levels, generate cGMP, and
potentiate the cGMP response to GnRH, suggests that cGMP could play
important cellular functions.
Pituitary Adenylate Cyclase-activating Polypeptide Stimulates
Nitric-oxide Synthase Type I Expression and Potentiates the cGMP
Response to Gonadotropin-releasing Hormone of Rat Pituitary
Gonadotrophs*
,
*
This work was supported in part by grants from the CNRS and
the Université Pierre et Marie Curie.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.
Recipient of funds from the Chancellerie des Universités de
Paris, the Association pour la Recherche sur le Cancer, and the Fondation pour la Recherche Médicale.
§
Recipient of funds from the Ministère de l'Education
Nationale, de la Recherche et de la Technologie, and the Association pour la Recherche sur le Cancer.
¶
To whom correspondence should be addressed: UMR-CNRS, 7079 Physiologie et Physiopathologie, Université P. & M. Curie, Case 256, 75252 Paris Cedex 05, France. Tel.: 33-1-44-27-26-48; Fax: 33-1-44-27-26-50; E-mail: Raymond.Counis@snv.jussieu.fr.
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