Vasoactive intestinal peptide, but not pituitary adenylate cyclase-activating peptide, modulates the responsiveness of the gonadotroph to LHRH in man

Hammond, P. J.; Talbot, Kevin; Chapman, Richard; Ghatei, M. A.; Bloom, Stephen R.

doi:10.1677/joe.0.1370529

Cited by 28 publications

(16 citation statements)

References 12 publications

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“…No adverse effects have been reported when given to humans with doses producing significant biologic effects. 16,17 In contrast to dexamethasone, PACAP may be safely given even in diabetic patients. PACAP might work in concert with other relevant neural and hormonal factors in feeding-induced insulin secretion.…”

Section: Discussionmentioning

confidence: 99%

Potential protective action of pituitary adenylate cyclase-activating polypeptide (PACAP38) on in vitro and in vivo models of myeloma kidney injury

Arimura

Batuman

2006

Blood

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The most common type of renal injury in multiple myeloma is chronic tubulointerstitial nephropathy associated with casts in tubule lumens, an entity referred to as "myeloma kidney" that often progresses to end-stage kidney diseases. Myeloma kidney is associated with a significant increase in all-cause mortality, yet no effective intervention, except a limited use of steroid, is available. Here, we report that pituitary adenylate cyclaseactivating polypeptide with 38 residues (PACAP38) dramatically prevents injury of cultured renal proximal tubule cells caused by myeloma light chains through suppression of proinflammatory cytokines production, by inhibiting p38 MAPK and translocation of NFB via both PAC 1 and VPAC 1 receptors. The suppressive effects of PACAP was as effective as dexamethasone in all of their cytokine assays and demonstrated both in vitro and in vivo. Furthermore, PACAP38 inhibits myeloma cell growth directly and may also indirectly by suppressing production of the growth factor, IL-6, from bone marrow stromal cells, that is stimulated by adhesion of myeloma cells. These findings render PACAP38 worth evaluation as a promising candidate for an effective and safe renoprotectant in myeloma kidney, and possibly other nephropathy, and also as a new antitumor agent in multiple myeloma. ( IntroductionMultiple myeloma is the sixth most common cancer in the United States. About 13 200 new cases of multiple myeloma were diagnosed in 2000. According to the US Renal Data System, renal morbidity from multiple myeloma is substantial. 1 Myeloma kidney disease was associated with 250% increase in all-cause mortality. 1 The kidney is vulnerable to pathogenic effects of monoclonal light chains in multiple myeloma and other disease associated with overproduction of immunoglobulin light chains. The most common type of renal injury in multiple myeloma is chronic tubulointerstitial nephropathy associated with casts in tubule lumens, an entity referred to as "myeloma kidney" that often progresses to end-stage kidney disease. 2,3 Although the mechanisms of cast formation have been clarified in studies that showed that certain types of light chains behave as ligand binding to defined sites on Tamm-Horsfall proteins, 4 the mechanisms responsible for chronic tubulointerstitial injury have only recently been explored. 5,6 These studies showed that increased endocytosis and overloading by myeloma light chains in proximal tubule cells produce inflammatory cytokines. These cytokine responses were mediated by activation of nuclear factor NFB and signaled through MAPKs, ERK1/2, JNK, and p38 MAPK. Despite improved understanding of the pathophysiology, no effective treatment is known for myeloma kidney except for a limited use of steroids.Pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP38) was isolated from ovine hypothalamic tissues based on the ability to stimulate adenylate cyclase in pituitary cell cultures. 7 PACAP38 is a new member of the vasoactive intestinal peptide (VIP) family of peptides. It is...

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Section: Discussionmentioning

confidence: 99%

Potential protective action of pituitary adenylate cyclase-activating polypeptide (PACAP38) on in vitro and in vivo models of myeloma kidney injury

Arimura

Batuman

2006

Blood

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“…The data we have regarding the influence of VIP on LH and FSH secretion are various. It is suggested that VIP could stimulate LH secretion [43][44][45]. The interactions between the pituitary thyroid axis and VIP have been very controversial in in vivo and in vitro studies.…”

Section: Discussionmentioning

confidence: 99%

Vasoactive Intestinal Peptide Can Modulate Immune and Endocrine Responses during Lipopolysaccharide-Induced Acute Inflammation

Bik

Woliñska-Witort

Chmielowska

et al. 2004

Neuroimmunomodulation

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Objectives: In many studies, it has been reported that vasoactive intestinal peptide (VIP) may play an important role in modulation of the immunological response. VIP can be produced by immunological cells, and also the receptors for this neuropeptide are present in many of these cells. The aim of our study was to estimate the effects of the administration of exogenous VIP on serum concentrations of proinflammatory cytokines [interleukin (IL)-6 and tumor necrosis factor (TNF)-α] and an anti-inflammatory cytokine (IL-10) during lipopolysaccharide (LPS)-induced acute inflammation. We also estimated the influence of VIP on pituitary [FSH, LH, TSH and prolactin (PRL)], thyroid (T3 and T4), adrenal (corticosterone) and gonadal (testosterone) hormones in response to LPS-induced acute inflammation. Methods: Male Wistar-Kyoto rats were divided into four groups, which received, respectively, placebo (0.9% NaCl), LPS, VIP and VIP with LPS. The TNF-α and IL-6 serum concentrations were measured after 2 h from the time of the administration of the agents, IL-10 was measured after 4 h, and the pituitary, thyroid, adrenal and gonadal hormone concentrations were measured after 2 and 4 h. Cytokine concentrations were estimated using ELISA tests, and hormone concentrations were measured using RIA tests. Results: In our experiments, LPS administration dramatically increased serum proinflammatory cytokine concentrations (TNF-α and IL-6) after 2 h and the anti-inflammatory cytokine (IL-10) after 4 h, as well as increasing the serum corticosterone concentration (after 2 and 4 h) and LH (after 2 h). LPS application decreased serum concentrations of T3 and TSH (both after 2 h), testosterone (after 2 and 4 h), FSH after 4 h and PRL after 4 h. VIP administration decreased the serum IL-10 concentration after 4 h and T3 concentration after 2 h and increased serum concentrations of FSH and corticosterone after 4 h. VIP administrated simultaneously with LPS decreased the LPS-induced increase in IL-6 and corticosterone concentrations (consecutively after 2 and 4 h). VIP also enhanced LPS-induced thyroid hormone (T3 and T4) suppression after 4 h and testosterone suppression after 4 h. Conclusion: We conclude that VIP can modulate not only immune responses but also hormonal responses during acute inflammation.

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“…Differential reduction in gonadotropin levels in VIP KO animals when compared with WT VIP action on pituitary LH and FSH secretion has long been controversial (Hammond et al 1993, Sawangjaroen et al 1997. LH and FSH could subsequently affect gonad development and functions, especially testicular steroidogenesis and spermatogenesis.…”

Section: Absence Of Vip Is Associated With Very Low Testosterone Levementioning

confidence: 99%

Lack of vasoactive intestinal peptide reduces testosterone levels and reproductive aging in mouse testis

Lacombe¹,

Lelièvre²,

Roselli³

et al. 2007

Journal of Endocrinology

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The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide have long been considered as putative regulators of testicular functions. In vitro evidence suggests that VIP could play an important role in testosterone biosynthesis. However, the endogenous role of VIP on testicular functions remained to be demonstrated. In C57BL/6 mice exhibiting a complete disruption of the VIP gene, we first observed here that serum testosterone levels were lower than those of WT littermates. At the age of 4 months, this phenotype was accompanied with a reduction of expression of StAR and 3-b-hydroxysteroid dehydrogenase (3b-HSD) in the testis. In addition, serum levels of FSH but not LH were reduced in young knock-out (KO) males. Testicular anatomy also revealed a higher percentage of degenerated seminiferous tubules in the 4-month-old VIP KO animals when compared with WT. In 15-month-old animals, control males showed typical testicular aging, including a severe degeneration of seminiferous tubules, a dramatic decrease in serum levels of testosterone, and a reduction in StAR and 3b-HSD gene expression. In age-matching VIP KO males, the levels of serum testosterone and steroidogenic enzymes were still very low. Interestingly, in contrast to that observed in young mice, testicular degeneration at 15 months was significantly less severe in VIP KO than WT mice. All together, these results suggest that 1) VIP is an important factor for regulating testosterone biosynthesis and FSH secretion and 2) VIP may influence testicular aging.

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Vasoactive intestinal peptide, but not pituitary adenylate cyclase-activating peptide, modulates the responsiveness of the gonadotroph to LHRH in man

Cited by 28 publications

References 12 publications

Potential protective action of pituitary adenylate cyclase-activating polypeptide (PACAP38) on in vitro and in vivo models of myeloma kidney injury

Potential protective action of pituitary adenylate cyclase-activating polypeptide (PACAP38) on in vitro and in vivo models of myeloma kidney injury

Vasoactive Intestinal Peptide Can Modulate Immune and Endocrine Responses during Lipopolysaccharide-Induced Acute Inflammation

Lack of vasoactive intestinal peptide reduces testosterone levels and reproductive aging in mouse testis

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