PLC-α: A common mediator of the action of estrogen and other hormones?

doi:10.1016/0303-7207(91)90136-G

Molecular and Cellular Endocrinology

Volume 80, Issues 1–3, September 1991, Pages C187-C191

https://doi.org/10.1016/0303-7207(91)90136-G Get rights and content

Abstract

The phosphatidyl inositol (PI) second messenger pathway may mediate diverse effects of estrogen, including its potentiation of the effects of other hormones. Both estradiol (E₂) and luteinizing hormone-releasing hormone (LHRH) induce a putative isoform of PI-specific phospholipase C-α (PLC-α). PLC-α catalyzes PI hydrolysis, which in turn can increase protein kinase C (PKC) activation, Ca²⁺ mobilization, and arachidonic acid metabolism. Estrogen activates the PI pathway, and components of the PI pathway can mimic or enhance some effects of estrogen. Furthermore, estrogen potentiates effects of several hormones (e.g., LHRH, prolactin, and insulin) which can also act through the PI system. PLC-α may therefore provide a common second messenger pathway mediating the potentiation by E₂ of the effects of other hormones; in addition it may also mediate some or all of the many actions of E₂, since components of the PI pathway can have secretory, trophic, toxic, and neuromodulatory effects.

References (65)

C.F. Bennett et al.
J. Biol. Chem.
(1987)
J.L. Boyer et al.
Trends Pharmacol. Sci.
(1989)
R.N. Etindi et al.
Biochim. Biophys. Acta
(1988)
L.C. Krey et al.
Mol. Cell. Endocrinol.
(1990)
M.A. Lynch et al.
Neurosci. Lett.
(1988)
P.W. Majerus et al.
Cell
(1990)
C.V. Mobbs et al.
Current Topics Membr. Transp.
(1987)
C.V. Mobbs et al.
Mol. Cell. Endocrinol.
(1989)
C.V. Mobbs et al.
J. Neurosci. Methods
(1989)
C.V. Mobbs et al.
Pharmacol. Biochem. Behav.
(1989)

A.Y.C. Liu et al.

Cited by (45)

Steroid hormone-mediated regulation of sexual and aggressive behaviour by non-genomic signalling
2023, Steroids
Sex and aggression are well studied examples of social behaviours that are common to most animals and are mediated by an evolutionary conserved group of interconnected nuclei in the brain called the social behaviour network. Though glucocorticoids and in particular estrogen regulate these social behaviours, their effects in the brain are generally thought to be mediated by genomic signalling, a slow transcriptional regulation mediated by nuclear hormone receptors. In the last decade or so, there has been renewed interest in understanding the physiological significance of rapid, non-genomic signalling mediated by steroids. Though the identity of the membrane hormone receptors that mediate this signalling is not clearly understood and appears to be different in different cell types, such signalling contributes to physiologically relevant behaviours such as sex and aggression. In this short review, we summarise the evidence for this phenomenon in the rodent, by focusing on estrogen and to some extent, glucocorticoid signalling. The use of these signals, in relation to genomic signalling is manifold and ranges from potentiation of transcription to the possible transduction of environmental signals.
Regulation of cocaine-related behaviours by estrogen and progesterone
2022, Neuroscience and Biobehavioral Reviews
Citation Excerpt :
One mechanism of regulation of cellular function by ERs is initiation of intracellular signalling cascades. E2 activates phospholipase C (PLC)/protein kinase C (PKC) (Mobbs et al., 1991), mitogen-activated protein kinase (MAPK) (Singh et al., 1999), cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) (Aronica et al., 1994; Balthazart, 2021), and phosphatydilinositol 3 kinase (PI3K) (Etgen et al., 2006) intracellular signalling cascades within seconds or minutes [see (Kokane and Perrotti, 2020) for a discussion of these pathways in the context of E2-potentiated responsivity to drugs]. E2 or the membrane-impermeable E2-bovine serum albumin (BSA) conjugate increased baseline MAPK-dependent phosphorylation of cAMP response element (CRE)-binding protein (CREB) and inhibited K-induced pCREB in cultured female rat hippocampal neurons, indicating that central E2-induced intracellular signalling is initiated at the plasma membrane (Boulware et al., 2005).
Women are more sensitive to cocaine craving elicited by stimuli associated with relapse. Ovarian hormones modulate cocaine craving and may therefore function as risk factors or therapeutic agents for the development and treatment of cocaine use disorder, respectively. We review herein the neuropharmacological effects of the steroid hormones 17ß-estradiol, progesterone, and allopregnanolone, a progesterone metabolite, in relation to their effects on cocaine-induced locomotion, behavioural sensitization, conditioned place preference, and reinstatement of cocaine seeking. In general, the literature suggests that female rats are more sensitive to these cocaine-induced behaviours than males and that 17ß-estradiol facilitates the expression of these sex differences. Alternatively, in females, exogenous progesterone attenuates cocaine conditioned place preference, reinstatement, and possibly behavioural sensitization, either on its own or after conversion to allopregnanolone. These opposing effects of 17ß-estradiol and progesterone/allopregnanolone involve endocannabinoid, γ-aminobutyric acid, dopamine, and glutamate transmission in the medial prefrontal cortex and striatum. We conclude that 17ß-estradiol may be a risk factor for various components of cocaine use disorder in women, whereas progesterone and allopregnanolone may be potential treatment options.
Estrogen Regulation of Neurotransmitter and Growth Factor Signaling in the Brain
2017, Hormones, Brain and Behavior: Third Edition
Estrogens act in diverse brain regions to regulate reproductive and nonreproductive behaviors and neuronal functions, including mood, cognition, pain, seizures, sensorimotor integration, energy homeostasis, and neural degeneration due to aging, ischemia, and other insults. This chapter reviews evidence that estrogens act at multiple levels in many brain regions to modify synaptic neurotransmission. Identified targets of estrogen action include classical neurotransmitters and diverse peptides that function as neuromodulators. Estrogens act both presynaptically, regulating transmitter availability and/or release, and postsynaptically, governing cellular responses to released transmitter. Hormone-dependent alterations in neural responses to transmitters involve regulation of transmitter receptor expression and the efficacy of transmembrane signal transduction. Estrogens also determine which intracellular signal transduction pathways are activated when neurotransmitters bind their receptors. Emerging evidence suggests that estrogens can activate downstream molecules associated with growth factors and modify the crosstalk between growth factor and neurotransmitter receptor signaling pathways. Therefore, we also summarize findings indicating that physiologically relevant cross talk occurs among estrogen receptor, neurotransmitter receptor, and growth factor receptor signal transduction pathways. The data show that estrogens act throughout the brain to modulate neuronal excitability, synaptic efficacy, and neurogenesis, suggesting that these are fundamental mechanisms of steroid hormone action in the brain.
Importance of sex to pain and its amelioration; relevance of spinal estrogens and its membrane receptors
2012, Frontiers in Neuroendocrinology
Citation Excerpt :
In fact, caveolins are essential for many membrane ERα responses (Luoma et al., 2008), e.g., functional coupling of ERα to mGluR1 (Boulware et al., 2007). Stimulation of plasma membrane ERs is coupled to the activation of the same spectrum of signaling molecules that participate in most membrane initiated signaling cascades, e.g., protein kinase A, protein kinase B, protein kinase C, phospholipase C, inositol trisphosphate, MAPK, ERK, tyrosine kinases, etc. (Aronica et al., 1994; Bi et al., 2000; Cardona-Gomez et al., 2002; Gu and Moss, 1996; Lieberherr et al., 1993; Marino et al., 1998; Mendoza et al., 1995; Minami et al., 1990; Mobbs et al., 1991; Nabekura et al., 1986; Qiu et al., 2003; Razandi et al., 1999; Singh et al., 1999; Szego and Davis, 1967; Toran-Allerand et al., 1999; Watters et al., 1997; Zhou et al., 1996). Estrogens can also modulate neuronal membrane excitability by gating calcium currents (Bologa et al., 2006; Chaban et al., 2003; Improta-Brears et al., 1999; Lee et al., 2002; Mermelstein et al., 1996; Morley et al., 1992; Revankar et al., 2005).
Estrogens have a multitude of effects on opioid systems and are thought to play a key role in sexually dimorphic nociception and opioid antinociception. Heretofore, classical genomic actions of estrogens are largely thought to be responsible for the effects of these steroids on nociception and opioid antinociception. The recent discovery that estrogens can also activate estrogen receptors that are located in the plasma membrane, the effects of which are manifest in seconds to minutes instead of hours to days has revolutionized our thinking concerning the ways in which estrogens are likely to modulate pain responsiveness and the dynamic nature of that modulation. This review summarizes parameters of opioid functionality and nociception that are subject to modulation by estrogens, underscoring the added dimensions of such modulation that accrues from rapid membrane estrogen receptor signaling. Implications of this mode of signaling regarding putative sources of estrogens and its degradation are also discussed.
Membrane estrogen receptors activate metabotropic glutamate receptors to influence nervous system physiology
2009, Steroids
Until recently, the idea that estradiol could affect cellular processes independent of nuclear estrogen receptors was often dismissed as artifact. This in spite of a large number of carefully controlled studies performed both within and outside the nervous system demonstrating estrogens regulate various intracellular signaling pathways by acting at the membrane surface of cells and/or at biological rates incompatible with the time course of genomic-initiated events. The concept that estradiol can act on surface membrane receptors to regulate nervous system function is now far less controversial. However, there is evidence that there may be multiple types of estrogen receptors on the membrane surface of cells. Determining the physiological relevance of each of these receptors is currently underway. Two important membrane estrogen receptors are in fact the classical estrogen receptor-alpha (ERα) and estrogen receptor-beta (ERβ) proteins, which is somewhat surprising based upon their well-established role in nuclear gene transcription. This review will focus on the mechanism by which surface-localized ERα and ERβ stimulate intracellular signaling events in cells of the nervous system through activation of metabotropic glutamate receptors (mGluRs). This mechanism of estrogen receptor function also requires caveolin proteins, which provide the subcellular compartmentalization of the particular signaling components required for appropriate cell stimulation. The review will conclude with several examples of physiological processes under the apparent regulation of ER/mGluR signaling.
Estrogen regulation of neurotransmitter and growth factor signaling in the brain
2009, Hormones, Brain and Behavior Online
Estrogens act in diverse brain regions to regulate reproductive and nonreproductive behaviors and neuronal functions, including mood, cognition, pain, seizures, sensorimotor integration, energy homeostasis, and neural degeneration due to aging, ischemia, and other insults. This chapter reviews evidence that estrogens act at multiple levels in many brain regions to modify synaptic neurotransmission. Identified targets of estrogen action include classical neurotransmitters and diverse peptides that function as neuromodulators. Estrogens act both presynaptically, regulating transmitter availability and/or release, and postsynaptically, governing cellular responses to released transmitter. Hormone-dependent alterations in neural responses to transmitters involve regulation of transmitter receptor expression and the efficacy of transmembrane signal transduction. Estrogens also determine which intracellular signal transduction pathways are activated when neurotransmitters bind their receptors. Emerging evidence suggests that estrogens can activate downstream molecules associated with growth factors and modify the crosstalk between growth factor and neurotransmitter receptor signaling pathways. Therefore, we also summarize findings indicating that physiologically relevant cross talk occurs among estrogen receptor, neurotransmitter receptor, and growth factor receptor signal transduction pathways. The data show that estrogens act throughout the brain to modulate neuronal excitability, synaptic efficacy, and neurogenesis, suggesting that these are fundamental mechanisms of steroid hormone action in the brain.

View all citing articles on Scopus

View full text

At the cutting edgePLC-α: A common mediator of the action of estrogen and other hormones?

Abstract

J. Biol. Chem.

Trends Pharmacol. Sci.

Biochim. Biophys. Acta

Mol. Cell. Endocrinol.

Neurosci. Lett.

Cell

Current Topics Membr. Transp.

Mol. Cell. Endocrinol.

J. Neurosci. Methods

Pharmacol. Biochem. Behav.

Neurosci. Lett.

Food Chem. Toxicol.

Mol. Cell. Endocrinol.

Prostaglandins Leukotrienes Med.

Cell

Endocrinology

Science

Nature

Nature

Biol. Reprod.

J. Endocrinol.

Reprod. Nutr. Dev.

Neuroendocrinology

Endocrinology

Soc. Neurosci. Abstract

Science

J. Reprod. Fertil.

Science

J. Endocrinol.

Soc. Neurosci. Abstracts

At the cutting edge
PLC-α: A common mediator of the action of estrogen and other hormones?