Facilitated calcium mobilization and inositol phosphate production in the priming effect of LH-releasing hormone in the rat

Mitchell, Rory; Johnson, Mark; Ogier, Sally-Ann; Fink, George

doi:10.1677/joe.0.1190293

Cited by 31 publications

(17 citation statements)

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“…Similar delayed LH responses to phorbol esters have been observed from both perifused pituitary glands (15, 16) and pituitary cells (22) and it has been suggested that protein kinase C plays an important role in the potentiation ofthe LH response to GnRH (16). Not only does GnRH stimulate phosphoinositide turnover (23), but GnRH self-priming is associated with an enhanced GnRH-induced inositol phosphate production (24).…”

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confidence: 58%

Stimulation of Luteinizing Hormone‐Beta Messenger Ribonucleic Acid and Post‐Translational Modification of Luteinizing Hormone Isoforms by Second Messengers Mediating the Action of Gonadotrophin‐Releasing Hormone

Leigh

Wilson

Edger

et al. 1991

J Neuroendocrinology

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K~Y words second messengers, luteinizing hormone, luteinizing hormone pleiomorphisrn luteinizing hormone-/I messenger ritmnucleic acid. gonadotrophin-releasing hormone Abstract Several second messenger systems have been implicated in mediating the action of gonadotrophin-releasing hormone on the pituitary gonadotrophs and numeroLis studies have shown that activation of these systems induces luteinizing hormone (LH) secretion. However, it is not known how gonadotrophin-releasing hormone or the second messenger systems induce d e novo LH biosynthesis and post-translational modification of the hormone. In these experiments hemipituitary glands have been perifused with drugs which activate second messengers or stimulate protein kinase C directly. The LH secretory responses have been correlated with measurements of common CI and LH/I mRNA and t h e molecular species of LH which were present in t h e pituitary perifusate after exposure to the drugs.Gonadotrophin-releasing hormone (50 ng/ml, 42 nM), with and without the presence of extracellular Ca2'% the Ca2+ ionophore, A23187 (IOpM), and phorbol 12-myristate (1 pM) all stimulated an increase in LHP mRNA compared with controls and the appearance of a different isoform of LH to that found stored in and released from the unstimulated pituitary gland. Phospholipase C was without effect on LH/I mRNA levels and showed minimal efficacy in inducing the appearance of the different LH isoform.The intcraction of gonadotrophin-releasing hormone (GnKH) with specific receptors on the pituitary gonadotroph ultimately ind iiccs both luteinizing hormone (LH) release and synthesis. Thcse effects are mediated by second messenger systems, many of bcliich have been implicated in the LH secretory process. These include the Ca2+-ealmodulin system and phosphoinositide hydrolycij generating diacylglycerol and inositol trisphosphate and arachidonic acid (I).While it is clear that the action of GnRH involves more than a single second messenger system, the precise role of these second mcsacngers in mediating the initial rapid LH response to GnRH and o r the second phase protein synthesis-dependent rclease (2) has not yet been fully established. Even less is known about thc showcd that phorbol estcrs, like GnRH, can incrcase LHP mRNA levels in pituitary cell cultures and they suggest that protein kinase C may, in part, regulate LH biosynthesis. Furthermore, it has been shown that both CAMP and phorbol esters mimic G n R H in enhancing glycosylation of LH ( 5 , 6) thus indicating that both the transcriptional and post-translational effccts of G n R H arc mediated by similar second messenger pathways.In an attempt to establish intracellular mechanisms which may be involved in stimulating LH biosynthesis and post-translational modifications, we have perifused hemipituitary glands (in thc prcscncc of a protcase inhibitor) with a varicty of drugs known to activatc the Ca2+-calmodulin systcm or protein kinase C. The LH responses of the pituitary glands to these secretagogues have been measured and c...

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confidence: 58%

Stimulation of Luteinizing Hormone‐Beta Messenger Ribonucleic Acid and Post‐Translational Modification of Luteinizing Hormone Isoforms by Second Messengers Mediating the Action of Gonadotrophin‐Releasing Hormone

Leigh

Wilson

Edger

et al. 1991

J Neuroendocrinology

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“…Cells in G2/Mphase (%) coordinated effects on GnRH receptor number and on post-receptor signalling (Clayton et al 1980, Mitchell et al 1988, Drouva et al 1990, Leong & Thorner 1991. In an earlier study we demonstrated that oestradiol causes a dose-dependent increase in [ 3 H]thymidine incorporation and cell number in T3-1 cells ).…”

Section: Cells In S-phase (%)mentioning

confidence: 99%

“…The direct effects have been extensively studied in primary cultures of rat pituitary cells in which oestradiol can amplify GnRH-stimulated gonadotrophin secretion (Tang et al 1982) and can increase GnRH receptor number (Clayton 1989) and influence gonadotrophin subunit expression (Ramey et al 1987, Phillips et al 1988. In terms of GnRH signalling, oestradiol has been shown to influence the Ca 2+ response to GnRH (Leong & Thorner 1991) and the effects of GnRH on Ca 2+ mobilisation and Ins(1,4,5)P 3 generation are increased in cells from pro-oestrous rats and reduced in those from ovariectomised rats (Mitchell et al 1988). Moreover, oestradiol has been shown to increase phorbol ester-stimulated gonadotrophin secretion and anterior pituitary levels of PKC (Drouva et al 1990).…”

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confidence: 99%

Oestradiol is a potent mitogen and modulator of GnRH signalling in alphaT3-1 cells: are these effects causally related?

Williams

Brooks²,

Aldridge³

et al. 2000

Journal of Endocrinology

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GnRH acts via phospholipase C (PLC) activating G-protein coupled receptors to stimulate secretion of gonadotrophins from gonadotrophs. These cells are also regulated by gonadal steroids, which act centrally to influence GnRH secretion, and peripherally to modulate GnRH action. We have shown that oestradiol can stimulate proliferation and modulate GnRH-stimulated [ H]thymidine incorporation was not stimulated by oestradiol but was reduced to <2% of control by the oestrogen antagonist, raloxifene. The inhibitory effect of 10 or 1000 nM raloxifene was reversed competitively by oestradiol. A similar pattern of effects was seen when effects of oestradiol and raloxifene on the proportion of cells in the S-phase of the cell cycle (as measured by flow cytometry of propidium iodide-labelled cells) and on oestrogen receptor activity (as measured by transactivation of the oestrogen-response elements in the vitellogenin promoter) were quantified. In addition, RT-PCR revealed expression of and (but not 2) subtypes of oestrogen receptors. Thus, oestrogen is an essential mitogen for T3-1 cells, its mitogenic effect is oestrogen receptor mediated and is associated with a marked alteration of cell cycle distribution, and the full extent of these effects are best revealed in the presence of raloxifene. Using this strategy, we found that cells cultured for 4 days with 10 nM raloxifene expressed GnRH receptors (K d for 125 I-buserelin 4·33 nM) and that their activation by GnRH caused a concentration-dependent increase in 3 H]IP x and Ins(1,4,5)P 3 approximately 4-fold. The effects of oestradiol on GnRH receptor number and signalling were not, however, mimicked by culture for 2 days in medium with 10% FCS and the S-phase blocker, thymidine (15 mM). This treatment increased the proportion of cells in the S-phase 2-to 3-fold but did not alter GnRH receptor number or signalling. Other treatments which altered cell cycle transition (hydroxyurea, colcemid, methotrexate) also failed to alter GnRH receptor number or signalling and no correlation was seen between GnRH receptor number or GnRHstimulated [ 3 H]IP x accumulation and the proportion of cells in the S-phase or G2/M-phases of the cell cycle. Thus, oestradiol has pronounced effects on GnRH signalling, proliferation and cell cycle distribution in T3-1 cells, but these trophic effects do not underlie the modulation of GnRH signalling.

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“…AAD VAN (8); (iii) LH-RH and substance P both facilitate the estrogen-regulated behavior lordosis (9), and the phosphoinositol pathway is implicated in mediating effects of these peptides (10). We therefore propose that HIP-70 is a specific hormone-induced isoform of the phosphoinositol-specific phospholipase C isoenzyme, PLC-a.…”

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confidence: 99%

HIP-70: An Isoform of Phosphoinositol-Specific Phospholipase C—α

Mobbs

Fink

Pfaff

1990

Science

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depth. However, Deutsch and Ramachandran's example of a crumpled newspaper clearly shows that this is not the only factor involved. In this case there is an abundance of high contrast local disparity information provided by the printed letters, yet the pseudoscopic image cannot be reversed in depth. This is also true if the words and letters are completely unintelligible. Likewise, pseudoscopic viewing of the normal face of our original figure 5 (1), upsidedown or partially covered, does not make the nose reverse. We therefore feel confident that the binocular interpretation of texture perspective (2) and not familiarity counter-

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Facilitated calcium mobilization and inositol phosphate production in the priming effect of LH-releasing hormone in the rat

Cited by 31 publications

References 0 publications

Stimulation of Luteinizing Hormone‐Beta Messenger Ribonucleic Acid and Post‐Translational Modification of Luteinizing Hormone Isoforms by Second Messengers Mediating the Action of Gonadotrophin‐Releasing Hormone

Stimulation of Luteinizing Hormone‐Beta Messenger Ribonucleic Acid and Post‐Translational Modification of Luteinizing Hormone Isoforms by Second Messengers Mediating the Action of Gonadotrophin‐Releasing Hormone

Oestradiol is a potent mitogen and modulator of GnRH signalling in alphaT3-1 cells: are these effects causally related?

HIP-70: An Isoform of Phosphoinositol-Specific Phospholipase C—α

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