Novel Aspects of GnRH‐Induced Intracellular Signaling and Secretion in Pituitary Gonadotrophs

Stojilković, Stanko S.; Catt, Kevin J.

doi:10.1111/j.1365-2826.1995.tb00711.x

Cited by 91 publications

(60 citation statements)

References 110 publications

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“…Many of the genomic effects of GnRH in its neuroendocrine target cells are believed to be mediated by the activation of MAPKs, which convey GnRH signaling from the cell surface to the nucleus for regulation of genes controlling the functions of GnRH neurons and pituitary gonadotropes (1,8). However, the roles of intermediate signaling molecules such as Pyk2 and the EGF-R in this pathway have not been clearly defined.…”

Section: Discussionmentioning

confidence: 99%

“…Immortalized GnRH-producing neurons (GT1-7 neurons) express several G protein-coupled receptors (GPCRs), including those for GnRH and luteinizing hormone/ human chorionic gonadotropin (2,3), as well as ␣-and ␤-adrenergic (4), muscarinic (5), and serotonergic receptors (6). These cells retain many of the characteristics of the native GnRH neurons, including the ability to maintain pulsatile GnRH release (1,3). Recent evidence suggests that the autocrine action of GnRH on hypothalamic GnRH neurons is involved in the mechanism of pulsatile GnRH secretion (3).…”

mentioning

confidence: 99%

“…The major signal transduction pathways in cells expressing GnRH receptors are initiated by activation of phospholipase C. The consequent calcium (Ca 2ϩ ) mobilization and activation of protein kinase C (PKC) by GnRH are key elements in the hypothalamic control of gonadotropin secretion from the anterior pituitary gland (1,3,5). Activation of PKC and Ca 2ϩ mobilization during GnRH receptor stimulation are also responsible for mediating downstream signals leading to activation of extracellularly regulated mitogen-activated protein kinases (ERK1/2 MAPKs) that transmit signals from the cell surface to the nucleus to regulate transcriptional and other processes (7)(8)(9)(10)(11)(12)(13).…”

mentioning

confidence: 99%

“…The pulsatile delivery of GnRH to the anterior pituitary gland is essential to maintain the circulating gonadotropin profiles that are necessary for normal reproductive function. In addition to regulating pituitary gonadotropin release, GnRH has extrapituitary actions in neural and nonneural tissues and in several types of tumor cells (1). Immortalized GnRH-producing neurons (GT1-7 neurons) express several G protein-coupled receptors (GPCRs), including those for GnRH and luteinizing hormone/ human chorionic gonadotropin (2,3), as well as ␣-and ␤-adrenergic (4), muscarinic (5), and serotonergic receptors (6).…”

mentioning

confidence: 99%

“…The hypothalamic decapeptide, gonadotropin releasing hormone (GnRH), 1 is a primary regulatory factor in the neuroendocrine control of reproduction and is released in an episodic manner from the hypothalamic GnRH neurons. The pulsatile delivery of GnRH to the anterior pituitary gland is essential to maintain the circulating gonadotropin profiles that are necessary for normal reproductive function.…”

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confidence: 99%

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Dependence of Gonadotropin-releasing Hormone-induced Neuronal MAPK Signaling on Epidermal Growth Factor Receptor Transactivation

Shah¹,

Soh²,

Catt³

2003

Journal of Biological Chemistry

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The hypothalamic decapeptide, gonadotropin-releasing hormone (GnRH), utilizes multiple signaling pathways to activate extracellularly regulated mitogen-activated protein kinases (ERK1/2) in normal and immortalized pituitary gonadotrophs and transfected cells expressing the GnRH receptor. In immortalized hypothalamic GnRH neurons (GT1-7 cells), which also express GnRH receptors, GnRH, epidermal growth factor (EGF), and phorbol 12-myristate 13-acetate (PMA) caused marked phosphorylation of ERK1/2. This action of GnRH and PMA, but not that of EGF, was primarily dependent on activation of protein kinase C (PKC), and the ERK1/2 responses to all three agents were abolished by the selective EGF receptor kinase inhibitor, AG1478. Consistent with this, both GnRH and EGF increased tyrosine phosphorylation of the EGF receptor. GnRH and PMA, but not EGF, caused rapid phosphorylation of the proline-rich tyrosine kinase, Pyk2, at Tyr 402 . This was reduced by Ca 2؉ chelation and inhibition of PKC, but not by AG1478. GnRH stimulation caused translocation of PKC␣ and -⑀ to the cell membrane and enhanced the association of Src with PKC␣ and PKC⑀, Pyk2, and the EGF receptor. The Src inhibitor, PP2, the C-terminal Src kinase (Csk), and dominant-negative Pyk2 attenuated ERK1/2 activation by GnRH and PMA but not by EGF. These findings indicate that Src and Pyk2 act upstream of the EGF receptor to mediate its transactivation, which is essential for GnRH-induced ERK1/2 phosphorylation in hypothalamic GnRH neurons.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Dependence of Gonadotropin-releasing Hormone-induced Neuronal MAPK Signaling on Epidermal Growth Factor Receptor Transactivation

Shah¹,

Soh²,

Catt³

2003

Journal of Biological Chemistry

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Regulation of exocytosis via release of Ca2+ from intracellular stores

Tse

1999

Bioessays

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The release of Ca2+ from intracellular stores is an important trigger for secretion in many cell types. Depending on the spatial relationship between the intracellular Ca2+ stores and the site of exocytosis, the Ca2+ signal can be very local or spread throughout the entire cell. Here, we review how the release of Ca2+ from inositol trisphospate (IP3)‐sensitive stores contributes differently to the stimulus‐secretion coupling in three types of secretory cells (acinar cells of the pancreas, gonadotrophs, and corticotrophs of the anterior pituitary gland). We propose that in both pancreatic acinar cells and pituitary gonadotrophs the IP3‐sensitive stores may be in close proximity to the sites of exocytosis such that the concentration of Ca2+ at these sites are transiently much higher than the average cytosolic Ca2+ concentration. In contrast, the local Ca2+ gradient is less prominent in pituitary corticotrophs. Finally, some recent technical developments that may contribute significantly to future investigations of local Ca2+ signals are discussed. BioEssays 21:861–865, 1999. © 1999 John Wiley & Sons, Inc.

show abstract

Regulation of exocytosis via release of Ca2 from intracellular stores

Tse¹,

Tse²

1999

Bioessays

View full text Add to dashboard Cite

The release of Ca(2+) from intracellular stores is an important trigger for secretion in many cell types. Depending on the spatial relationship between the intracellular Ca(2+) stores and the site of exocytosis, the Ca(2+) signal can be very local or spread throughout the entire cell. Here, we review how the release of Ca(2+) from inositol trisphospate (IP(3))-sensitive stores contributes differently to the stimulus-secretion coupling in three types of secretory cells (acinar cells of the pancreas, gonadotrophs, and corticotrophs of the anterior pituitary gland). We propose that in both pancreatic acinar cells and pituitary gonadotrophs the IP(3)-sensitive stores may be in close proximity to the sites of exocytosis such that the concentration of Ca(2+) at these sites are transiently much higher than the average cytosolic Ca(2+) concentration. In contrast, the local Ca(2+) gradient is less prominent in pituitary corticotrophs. Finally, some recent technical developments that may contribute significantly to future investigations of local Ca(2+) signals are discussed.

show abstract

Novel Aspects of GnRH‐Induced Intracellular Signaling and Secretion in Pituitary Gonadotrophs

Cited by 91 publications

References 110 publications

Dependence of Gonadotropin-releasing Hormone-induced Neuronal MAPK Signaling on Epidermal Growth Factor Receptor Transactivation

Dependence of Gonadotropin-releasing Hormone-induced Neuronal MAPK Signaling on Epidermal Growth Factor Receptor Transactivation

Regulation of exocytosis via release of Ca2+ from intracellular stores

Regulation of exocytosis via release of Ca2 from intracellular stores

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