C-type natriuretic peptide (CNP) effects on intracellular calcium [Ca2+]i in mouse gonadotrope-derived αT3-1 cell line

Fowkes, Robert C.; Forrest-Owen, W; Williams, B. A.; McArdle, Craig A.

doi:10.1016/s0167-0115(99)00066-x

Cited by 19 publications

(17 citation statements)

References 32 publications

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“…Basal promoter activity was greatest in the two gonadotroph cell lines, compared with the AtT-20 corticotroph cells that were previously used to examine Nppc transcription (Ohta et al 1993). Our novel observations that the proximal Nppc promoter appears responsive to GNRH build upon our earlier suggestion that GNRH and CNP are part of a reciprocal pathway, whereby one affects the expression and signalling of the other (McArdle et al 1994, Fowkes et al 1999, 2000. As expected, the stimulatory effect of GNRH on Nppc promoter activity involves PKC activity as well as calcium entry, in common with other gonadotroph-specific genes regulated by GNRH (Halvorson 2000).…”

Section: Discussionsupporting

confidence: 63%

“…Early studies characterising the expression profile of CNP suggested that the CNS and anterior pituitary are rich sources of CNP (Sudoh et al 1990, Komatsu et al 1991. Subsequent investigations revealed a gonadotrophspecific expression profile of CNP in the anterior pituitary (McArdle et al 1993(McArdle et al , 1994, and functional studies in aT3-1 gonadotrophs implicated a role for CNP in regulating GNRH signalling (Fowkes et al 1999). However, the molecular and functional characterisation of the natriuretic peptide system in gonadotrophs has remained poorly defined.…”

Section: Introductionmentioning

confidence: 99%

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Molecular characterisation and functional interrogation of a local natriuretic peptide system in rodent pituitaries, αT3-1 and LβT2 gonadotroph cells

Thompson

Chand²,

Jonas

et al. 2009

Journal of Endocrinology

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In the pituitary, C-type natriuretic peptide (CNP) has been implicated as a gonadotroph-specific factor, yet expression of the CNP gene (Nppc) and CNP activity in gonadotrophs is poorly defined. Here, we examine the molecular expression and putative function of a local gonadotroph natriuretic peptide system. Nppc, along with all three natriuretic peptide receptors (Npr1, Npr2 and Npr3), was expressed in both aT3-1 and LbT2 cells and primary mouse pituitary tissue, yet the genes for atrial-(ANP) and B-type natriuretic peptides (Nppa and Nppb) were much less abundant. Putative processing enzymes of CNP were also expressed in aT3-1 cells and primary mouse pituitaries. Transcriptional analyses revealed that the proximal 50 bp of the murine Nppc promoter were sufficient for GNRH responsiveness, in an apparent protein kinase C and calcium-dependent manner. Electrophoretic mobility shift assays showed Sp1/Sp3 proteins form major complexes within this region of the Nppc promoter. CNP protein was detectable in rat anterior pituitaries, and electron microscopy detected CNP immunoreactivity in secretory granules of gonadotroph cells. Pharmacological analyses of natriuretic peptide receptor activity clearly showed ANP and CNP are potent activators of cGMP production. However, functional studies failed to reveal a role for CNP in regulating cell proliferation or LH secretion. Surprisingly, CNP potently stimulated the human glycoprotein hormone a-subunit promoter in LbT2 cells but not in aT3-1 cells. Collectively, these findings support a role for CNP as the major natriuretic peptide of the anterior pituitary, and for gonadotroph cells as the major source of CNP expression and site of action.

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Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Molecular characterisation and functional interrogation of a local natriuretic peptide system in rodent pituitaries, αT3-1 and LβT2 gonadotroph cells

Thompson

Chand²,

Jonas

et al. 2009

Journal of Endocrinology

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“…Consistently, the anterior pituitary and in particular gonadotrophs, contain high concentrations of C-type natriuretic peptide (CNP), whereas a body of experimental data indicates that gonadotrophs, lactotrophs, corticotrophs, and folliculo-stellate cells but neither somatotrophs nor thyrotrophs express transmembrane type B natriuretic peptide receptor and respond to CNP by increasing cGMP production (67,70). How could PACAP stimulate the membrane-linked GC and induce the NOS/NO/sGC-independent production of cGMP remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…Based on other systems, cGMP may play a role in the regulation of cellular Ca 2ϩ metabolism and gene transcription through a small group of effectors, i.e. cGMP-dependent kinases and phosphodiesterases and cGMP-gated ion channels (67), the implication and roles of which remains to be explored in gonadotrophs.…”

Section: Discussionmentioning

confidence: 99%

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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“…Previous studies in T3-1 cells have shown that gonadotrophin-releasing hormone (GnRH), an important regulator of gonadotrophs and an essential regulator of reproductive function, can inhibit CNP-stimulated cGMP accumulation (McArdle et al 1993). However, CNP has recently been shown to inhibit GnRH-stimulated calcium mobilisation, suggesting that a reciprocal regulatory pathway exists between CNP and GnRH (Fowkes et al 1999).…”

Section: Introductionmentioning

confidence: 99%

C-type natriuretic peptide (CNP) effects in anterior pituitary cell lines: evidence for homologous desensitisation of CNP-stimulated cGMP accumulation in alpha T3-1 gonadotroph-derived cells

Fowkes

Forrest-Owen²,

McArdle³

2000

Journal of Endocrinology

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C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, has been found at its highest tissue concentrations in the anterior pituitary, where it is localised in gonadotrophs. Its specific guanylyl cyclasecontaining receptor, GC-B, is also expressed on several anterior pituitary cell types, and CNP potently stimulates cGMP accumulation in rat pituitary cell cultures and pituitary cell lines. The mouse gonadotroph-derived T3-1 cell line has been shown to express CNP as well as GC-B (but not GC-A) receptors, suggesting that CNP may well be an autocrine regulator of gonadotrophs.Comparing effects of three natriuretic peptides (atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and CNP) on cGMP accumulation in four pituitary cell lines ( T3-1, TtT-GF, AtT-20 and GH 3 ) we find that CNP is most potent and effective in T3-1 cells. In these cells, CNP-stimulated cGMP accumulation was found to desensitise during a 30 min exposure to CNP.Pretreatment with CNP for up to 6 h also caused a significant reduction in the ability of CNP to subsequently stimulate cGMP accumulation. This effect was receptor specific, because pretreatment with sodium nitroprusside (an activator of nitric oxide-sensitive guanylyl cyclase), or with ANP or BNP, did not cause desensitisation of CNP-stimulated cGMP accumulation. Protein kinase C activation with phorbol esters also inhibited CNPstimulated cGMP accumulation and such inhibition was also seen in cells desensitised by pretreatment with CNP. Thus it appears that the endogenous GC-B receptors of T3-1 cells are subject to both homologous and heterologous desensitisation, that the mechanisms underlying these forms of desensitisation are distinct, and that cGMP elevation alone is insufficient to desensitise GC-B receptors.

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C-type natriuretic peptide (CNP) effects on intracellular calcium [Ca2+]i in mouse gonadotrope-derived αT3-1 cell line

Cited by 19 publications

References 32 publications

Molecular characterisation and functional interrogation of a local natriuretic peptide system in rodent pituitaries, αT3-1 and LβT2 gonadotroph cells

Molecular characterisation and functional interrogation of a local natriuretic peptide system in rodent pituitaries, αT3-1 and LβT2 gonadotroph cells

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

C-type natriuretic peptide (CNP) effects in anterior pituitary cell lines: evidence for homologous desensitisation of CNP-stimulated cGMP accumulation in alpha T3-1 gonadotroph-derived cells

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