Phorbol Ester-Induced LH Release in Pituitary Gonadotrophs: Effects of Antagonists of Calmodulin and GnRH.

Izumi, Shun-ichiro; Iwashita, Mitsutoshi; Makino, Tsunehisa; Saito, Suguru; Sakamoto, Shoichi; Takeda, Yoshihiko; Nozawa, Shiro

doi:10.1507/endocrj1954.38.195

Cited by 3 publications

(3 citation statements)

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“…Early studies in gonadotrophs demonstrated that GnRH induces a change in localisation of CaM from the cytoplasm to the cell membrane and also indicated that it has a role in GnRH‐induced LH release, as well as in the expression of primary response genes, c‐ fos , c‐ jun and junB , . More recently, two of the better characterised signalling pathways downstream of CaM, the CaM‐dependent kinases (CaMKs) and the phosphatase, calcineurin, have been shown to play roles in transducing GnRH‐activated signals to gonadotrophin gene transcription and other aspects of gonadotroph function.…”

Section: Gonadotrophin‐releasing Hormone (Gnrh) the Gonadotroph And mentioning

confidence: 99%

“…CaMK, calmodulin-dependent kinase; CoR, receptor corepressor; ERK, extracellular-signal regulated kinase; HDAC, histone deacetylase; NFAT, nuclear factor of activated T-cells; PKA, protein kinase A; PKC, protein kinase C; PLC, phospholipase C; TORC, transducer of regulated CREB. c-fos, c-jun and junB, (22)(23)(24). More recently, two of the better characterised signalling pathways downstream of CaM, the CaMdependent kinases (CaMKs) and the phosphatase, calcineurin, have been shown to play roles in transducing GnRH-activated signals to gonadotrophin gene transcription and other aspects of gonadotroph function.…”

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confidence: 99%

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Gonadotrophin‐Releasing Hormone Signalling Downstream of Calmodulin

Melamed

Savulescu

Lim

et al. 2012

J Neuroendocrinology

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Gonadotrophin‐releasing hormone (GnRH) regulates reproduction via binding a G‐protein coupled receptor on the surface of the gonadotroph, through which it transmits signals, mostly via the mitogen‐activated protein (MAPK) cascade, to increase synthesis of the gonadotrophin hormones: luteinising hormone (LH) and follicle‐stimulating hormone (FSH). Activation of the MAPK cascade requires an elevation in cytosolic Ca2+ levels, which is a result of both calcium influx and mobilisation from intracellular stores. However, Ca2+ also transmits signals via an MAPK‐independent pathway, through binding calmodulin (CaM), which is then able to bind a number of proteins to impart diverse downstream effects. Although the ability of GnRH to activate CaM was recognised over 20 years ago, only recently have some of the downstream effects been elucidated. GnRH was shown to activate the CaM‐dependent phosphatase, calcineurin, which targets gonadotrophin gene expression both directly and indirectly via transcription factors such as nuclear factor of activated T‐cells and Nur77, the Transducer of Regulated CREB (TORC) co‐activators and also the prolyl isomerase, Pin1. Gonadotrophin gene expression is also regulated by GnRH‐induced CaM‐dependent kinases (CaMKs); CaMKI is able to derepress the histone deacetylase‐inhibition of β‐subunit gene expression, whereas CaMKII appears to be essential for the GnRH‐activation of all three subunit genes. Asides from activating gonadotrophin gene expression, GnRH also exerts additional effects on gonadotroph function, some of which clearly occur via CaM, including the proliferation of immature gonadotrophs, which is dependent on calcineurin. In this review, we summarise these pathways, and discuss the additional functions that have been proposed for CaM with respect to modifying GnRH‐induced signalling pathways via the regulation of the small GTP‐binding protein, Gem, and/or the regulator of G‐protein signalling protein 2.

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Section: Gonadotrophin‐releasing Hormone (Gnrh) the Gonadotroph And mentioning

confidence: 99%

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confidence: 99%

Gonadotrophin‐Releasing Hormone Signalling Downstream of Calmodulin

Melamed

Savulescu

Lim

et al. 2012

J Neuroendocrinology

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“…We previously reported that protein kinase C and calmodulin-dependent kinase participate in GnRH-induced LH release, and that either kinase system has a regulatory effect on the other [1]. This finding suggested that both kinase systems are connected by metabolic pathway(s), which transmits regulatory signals in a bi-directional way.…”

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confidence: 97%

Effect of GnRH Antagonists on Phorbol Ester-Induced LH Release from Rat Pituitary Gonadotrophs.

et al. 1994

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Abstract. We previously reported that a blockade of GnRH receptor activation inhibited the alreadyinitiated C-kinase pathway(s). We tried to investigate whether this finding is a general phenomenon or not. In this study, we employed three GnRH antagonists,]-GnRH (referred to as #1-, #2-, #3-GnRH antag., respectively). Each antagonist was examined for its potency against GnRH by analyzing its inhibitory effect on LH release from pituitary gonadotrophs as well as on the increase in the cytosolic Ca2+ concentration. As a result, the #1-GnRH antag. was found to be weaker than the other two compounds. Consistent with a previous study, the #3-GnRH antag. inhibited the action of TPA on LH release. However, independently of their potency as GnRH-antagonists, the two other antagonists had no inhibitory effect on TPA-induced LH release. While it is generally accepted that the C kinase pathway plays a major role in the GnRH-induced LH release, not all GnRH antagonists can inhibit LH release by blocking the already-activated C kinase system.

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Modulation of Calmodulin Gene Expression as a Novel Mechanism for Growth Hormone Feedback Control by Insulin-like Growth Factor in Grass Carp Pituitary Cells

Huo

Wang

et al. 2005

Endocrinology

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Calmodulin (CaM), the Ca2+ sensor in living cells, is essential for biological functions mediated by Ca2+-dependent mechanisms. However, modulation of CaM gene expression at the pituitary level as a means to regulate pituitary hormone synthesis has not been characterized. In this study we examined the functional role of CaM in the feedback control of GH by IGF using grass carp pituitary cells as a cell model. To establish the structural identity of CaM expressed in the grass carp, a CaM cDNA, CaM-L, was isolated from the carp pituitary using 3'/5' rapid amplification of cDNA ends. The open reading frame of this cDNA encodes a 149-amino acid protein sharing the same primary structure with CaMs reported in mammals, birds, and amphibians. This CaM cDNA is phylogenetically related to the CaM I gene family, and its transcripts are ubiquitously expressed in the grass carp. In carp pituitary cells, IGF-I and IGF-II induced CaM mRNA expression with a concurrent drop in GH transcript levels. These stimulatory effects on CaM mRNA levels were not mimicked by insulin and appeared to be a direct consequence of IGF activation of CaM gene transcription without altering CaM transcript stability. CaM antagonism and inactivation of calcineurin blocked the inhibitory effects of IGF-I and IGF-II on GH gene expression, and CaM overexpression also suppressed the 5' promoter activity of the grass carp GH gene. These results, as a whole, provide evidence for the first time that IGF feedback on GH gene expression is mediated by activation of CaM gene expression at the pituitary level.

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Phorbol Ester-Induced LH Release in Pituitary Gonadotrophs: Effects of Antagonists of Calmodulin and GnRH.

Abstract: Abstract.The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate

Cited by 3 publications

References 46 publications

Gonadotrophin‐Releasing Hormone Signalling Downstream of Calmodulin

Gonadotrophin‐Releasing Hormone Signalling Downstream of Calmodulin

Effect of GnRH Antagonists on Phorbol Ester-Induced LH Release from Rat Pituitary Gonadotrophs.

Modulation of Calmodulin Gene Expression as a Novel Mechanism for Growth Hormone Feedback Control by Insulin-like Growth Factor in Grass Carp Pituitary Cells

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