GnRH-dependent up-regulation of nitric oxide synthase I level in pituitary gonadotrophs mediates cGMP elevation during rat proestrus

Lozach, Anne; Garrel, Ghislaine; Lerrant, Yannick; Bérault, Annette; Counis, Raymond

doi:10.1016/s0303-7207(98)00135-x

Cited by 46 publications

(41 citation statements)

References 35 publications

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“…Regulation of the GnRH receptor gene followed a similar extreme dependency on the mode of GnRH stimulation previously revealed for the gonadodotropin β-subunit genes [17,40]. For both the GnRH receptor and the NOS I genes, evidence exists that the expression is up-regulated at proestrus of the ovarian cycle [31,44,45] suggesting a functional adaptation of the signalling machinery at this important physiological stage. GnRH receptor and NOS I promoters have been isolated and studies have characterised their tissue-specific and regulated expression in vitro using a transient transfection assay [36,[46][47][48][49][50][51] and/or in vivo using transgenesis [52][53][54].…”

Section: The Multigenic Impact Of Gnrh Stimulationsupporting

confidence: 60%

“…GnRH can also induce the activation of the mitogen associated protein kinase (MAPK) cascade through PKC to stimulate the expression of gonadotropin subunit genes [28,29]. Elevation of intracellular Ca 2+ also activates the NO synthase (NOS I) cascade (NOS I/NO/soluble guanylate cyclase) that results in the rapid production of cGMP [30,31], providing another example of an indirectly activated signalling pathway. GnRH can also induce phospholipases D and A2, as well as a delayed production of cAMP however, the mechanisms involved remain obscure.…”

Section: Gnrh Receptor Signallingmentioning

confidence: 99%

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Gonadotropin-releasing hormone and the control of gonadotrope function

et al. 2005

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-Normal gametogenesis and steroidogenesis is highly dependent on the pulsatile release of hypothalamic GnRH that binds high-affinity receptors present at the surface of pituitary gonadotrophs thereby triggering the synthesis and release of the gonadotropins LH and FSH. The mammalian GnRH receptor displays the classical heptahelical structure of G protein-coupled receptors with, however, a unique feature, the lack of a C-terminal tail. Accordingly, it does not desensitise sensu stricto, and internalises very poorly. It is now well established that GnRH stimulation induces the activation of a complex network of transduction pathways involved in the control of gonadotropin release and subunit gene expression. Other authors and ourselves have demonstrated that the GnRH action is associated with an increased complexity regarding gene regulation/cell function. Indeed GnRH affects the GnRH receptor gene itself and a number of additional genes that include some involved in cell signalling and auto-/paracrine regulation. The fact that GnRH regulates the expression of its own receptor, together with a host of other genes typically involved in its signal transduction cascades implies alteration/auto-adaptation in gonadotropic responsiveness. Furthermore, some of these genes respond differentially depending on whether the GnRH stimulation is intermittent or permanent suggesting specific roles in the dual process of activation/desensitisation. Thus, it can be assumed that the importance of pulsatility of GnRH action is closely related to, or dependent on, the inability of the GnRH receptor to desensitise. Moreover, multiple post-receptor events are crucial for both the regulation/plasticity of gonadotropic function and the maintenance of cell integrity.

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Section: The Multigenic Impact Of Gnrh Stimulationsupporting

confidence: 60%

Section: Gnrh Receptor Signallingmentioning

confidence: 99%

Gonadotropin-releasing hormone and the control of gonadotrope function

et al. 2005

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“…Moreover, this GnRH-dependent up-regulation of NOS I was distinct during an important physiologic event such as proestrus in female rats, leading to an amplified production of pituitary cGMP (18). Complementary to this, we have isolated a pituitary-specific promoter of NOS I that conferred responsiveness to GnRH as well as cAMP (34).…”

mentioning

confidence: 89%

“…Because, similar to GnRH, PACAP was able to regulate NOS I levels, we examined whether it was capable of inducing the rapid generation of cGMP and whether this action occurred through the NOS/NO/sGC cascade as shown for GnRH (18). For this, anterior hemipituitaries were incubated with or without PACAP for varying periods of time from 0 to 60 min.…”

Section: Pacap Stimulates Pituitary Production Of Cgmp a Rapid Effecmentioning

confidence: 99%

“…GnRH also induces the activation of the mitogen-activated protein kinase (MAPK) cascade and the production of cGMP. Recent studies have demonstrated that the latter two effects are indirect, the first resulting from the activation of PKC (16), and the second from the acute elevation of Ca 2ϩ resulting in the activation of nitric-oxide synthase (NOS) type I (17,18).…”

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confidence: 99%

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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

Garrel

Lozach²,

Bachir³

et al. 2002

Journal of Biological Chemistry

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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-bromocAMP 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.

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