Pituitary Adenyl Cyclase-Activating Peptide: A Hypophysiotropic Factor That Stimulates Proopiomelanocortin Gene Transcription, and Proopio-melanocortin-Derived Peptide Secretion in Corticotropic Cells

Boutillier, AL; Monnier, D.; Koch, Bernard; Jp, Loeffler

doi:10.1159/000126786

Cited by 32 publications

(17 citation statements)

References 32 publications

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“…Similar mechanisms have been reported with the somatolactotrope GH4C1 cell line, in which PACAP activates PRL gene expression through VPAC2-R in a cAMP/PKA/ERK/Rap1-dependent manner (Le Péchon-Vallée et al, 2000;Romano et al, 2003). In the corticotrope AtT20 cell line, PACAP mimics the effect of CRH; i.e., it stimulates AC activity and triggers both POMC gene transcription and adrenocorticotropin release Lutz-Bucher, 1992a, 1995;Boutillier et al, 1994;Braas et al, 1994;Aoki et al, 1997). In the folliculostellate cell line TtT/GF, PACAP increases IL-6 secretion .…”

Section: Effects Of Pituitary Adenylate Cyclase-activating Polypepsupporting

confidence: 55%

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

et al. 2009

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Section: Effects Of Pituitary Adenylate Cyclase-activating Polypepsupporting

confidence: 55%

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

et al. 2009

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“…PACAP also stimulates cAMP production in the AP. PACAP, therefore, could regulate pituitary corticotrophs directly (Boutillier et al 1994). CRF and AVP neurons in the parvocellular region of PVN project to the external zone of the ME (Seasholtz et al 1988, Gonzalez-Hernandez et al 2006.…”

Section: Discussionmentioning

confidence: 99%

“…PACAP also increases CRF mRNA levels in the parvocellular region of the PVN, suggesting that PACAP is involved in the positive regulation of CRF gene expression (Grinevich et al 1997). Therefore, it is suggested that PACAP might regulate the HPA axis by stimulation of CRF gene expression in the hypothalamus and through direct effects on pituitary corticotrophs (Boutillier et al 1994, Aoki et al 1997, Agarwal et al 2005. PACAP also activates AVP neurons of the PVN or SON via PAC1 receptor (Shioda et al 1997b, Nomura et al 1999.…”

Section: Introductionmentioning

confidence: 99%

Pituitary adenylate cyclase-activating polypeptide stimulates corticotropin-releasing factor, vasopressin and interleukin-6 gene transcription in hypothalamic 4B cells

Kageyama

Hanada

Iwasaki

et al. 2007

Journal of Endocrinology

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Corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) are the two major regulatory peptides in the hypothalamic-pituitary-adrenal axis. CRF, produced in the hypothalamic paraventricular nucleus (PVN) in response to stress, is secreted into the pituitary portal circulation, resulting in the release of adrenocorticotropic hormone from the anterior pituitary. AVP is synthesized in the PVN and supraoptic nucleus by various stressors. Hypothalamic 4B cells coexpress CRF and AVP. In 4B cells transfected with either a CRF or an AVP promoter-luciferase construct, forskolin increased the transcriptional activity of CRF or AVP. In the present study, we tried to determine whether pituitary adenylate cyclase-activating polypeptide (PACAP) regulates both CRF and AVP genes in the hypothalamic cells, because receptors for PACAP were expressed in the hypothalamic cells. PACAP stimulated activity of both CRF and AVP promoter via protein kinase A pathway. PACAP stimulated interleukin (IL)-6 promoter activity and the levels of IL-6 mRNA and protein. IL-6 stimulated activity of both CRF and AVP promoter in a dose-dependent manner. Finally, we found that the stimulatory effects of PACAP on both activities were significantly inhibited by treatment with anti-IL-6 monoclonal antibody. These data suggest that PACAP is involved in regulating the synthesis of IL-6 mRNA and IL-6 protein, and that the increase in endogenous IL-6 also contributes to stimulate the expression of both CRF and AVP genes. Taken together, these findings indicate that PACAP stimulates the transcription of CRF, AVP, and IL-6 genes in hypothalamic 4B cells.

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“…4) and through direct effects on pituitary corticotrophs [14,16,17]. PaCaP also stimulates both arginine vasopressin (aVP) gene transcription and mRNa expression via the camP-PKa pathway in hypothalamic 4B cells (Fig.…”

Section: Involvement Of Camp On Crf Gene Transcriptionmentioning

confidence: 99%

Regulatory Mechanisms Underlying Corticotropin-Releasing Factor Gene Expression in the Hypothalam

Kageyama

Suda

2009

Endocr J

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Abstract. The hypothalamic-pituitary-adrenal (HPa) axis is activated under various stressors. Corticotropin-releasing factor (CRF) plays a central role in controlling stress response, and regulating the HPa axis. CRF, produced in the hypothalamic paraventricular nucleus (PVN), stimulates adrenocorticotropic hormone (aCTH) production via CRF receptor type 1 (CRF 1 receptor) from the corticotrophs of the anterior pituitary (aP). Cyclic amP (camP)-protein kinase a (PKa) pathway takes a main role in stimulating CRF gene transcription. Forskolin and pituitary adenylate cyclaseactivating polypeptide (PaCaP) stimulate adenylate cyclase, intracellular camP production, and then CRF and arginine vasopressin (aVP) gene expression in hypothalamic 4B cells. Interleukin (IL)-6, produced in the PVN, both directly and indirectly stimulates CRF and aVP gene expression. estradiol may enhance the activation of CRF gene expression in response to stress. The HPa axis is regulated by a negative feedback mechanism, because glucocorticoids inhibit both CRF production in the hypothalamic PVN and aCTH production in the pituitary. Hypothalamic parvocellular neurons in the PVN are known to express glucocorticoid receptors, and glucocorticoids are able to regulate CRF gene transcription and expression levels directly in the PVN. glucocorticoids-dependent repression of camP-stimulated CRF promoter activity is mainly localized to promoter sequences between -278 and -233 bp. Both negative glucocorticoid regulatory element (ngRe) and serum response element (SRe) are involved in the repression of the CRF gene in the hypothalamic cells. Stimulation of crF gene in the hypothalamus Involvement of cAMP on CRF gene transcriptionCyclic amP (camP)-protein kinase a (PKa) pathway takes a main role in stimulating CRF synthesis [3][4][5]. There are several candidates for activating CRF neurons. For example, pituitary adenylate cyclase-activating polypeptide (PaCaP), a member of the secretin/glucagon/vasoactive intestinal peptide (VIP) family, is one of the putative hormones. Both PaCaP and the PaCaP-selective PaCaP receptor type 1 (PaC1 receptor) are known to be highly expressed in the hypothalamus, including the parvocellular and magnocellular subdivisions of the PVN, and the supraoptic nucleus (SON) [6,7]. PaCaP has shown to stimulate camP production in the aP [8]. PaCaP also increases CRF mRNa levels in the parvocellular region of the PVN, suggesting that PaCaP is involved in the positive regulation of CRF gene expression [9].

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Pituitary Adenyl Cyclase-Activating Peptide: A Hypophysiotropic Factor That Stimulates Proopiomelanocortin Gene Transcription, and Proopio-melanocortin-Derived Peptide Secretion in Corticotropic Cells

Cited by 32 publications

References 32 publications

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

Pituitary adenylate cyclase-activating polypeptide stimulates corticotropin-releasing factor, vasopressin and interleukin-6 gene transcription in hypothalamic 4B cells

Regulatory Mechanisms Underlying Corticotropin-Releasing Factor Gene Expression in the Hypothalam

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