Phorbol esters and forskolin infused into midbrain central gray facilitate lordosis

Mobbs, Charles V.; Rothfeld, Joel M.; Saluja, Raveen; Pfaff, Donald W.

doi:10.1016/0091-3057(89)90572-8

Cited by 27 publications

(5 citation statements)

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“…Previous studies have shown that PKC activation in the VMH can increase female sex behavior (Kow and Pfaff, 1998) but have not implicated a specific neurotransmitter. Estradiol may directly activate the phosphatidylinositol second messenger pathway leading to PKC activation (Mobbs et al, 1989) or act indirectly by inducing the expression of PKC isoforms or fos and jun complexes that can then interact with PKC to stimulate transcription at AP-1 sites (Gaub et al, 1990) as are found in the OTR promoter (Bale and Dorsa, 1998). It cannot be overlooked that inhibition of PKC may also affect other processes within the VMH that may alter lordosis behavior.…”

Section: Discussionmentioning

confidence: 99%

CNS Region-Specific Oxytocin Receptor Expression: Importance in Regulation of Anxiety and Sex Behavior

et al. 2001

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The oxytocin receptor (OTR) is differentially expressed in the CNS. Because there are multiple mechanisms by which the OTR can be transcriptionally induced, we hypothesized that differences in OTR expression may be explained by activation of distinct signal transduction pathways and may be critical for the control of anxiety and sex behaviors. To determine the regulation and functional significance of this expression, we infused female rats with modifiers of protein kinases before assaying for behavior and oxytocin receptor binding. In the ventromedial nucleus of the hypothalamus (VMH), estrogen-dependent induction of oxytocin receptors required protein kinase C activation, and oxytocin infused here promoted female sex behavior but had no effect on anxiety. In contrast, dopamine controlled tonic oxytocin receptor expression in the central nucleus of the amygdala (cAmyg) through activation of protein kinase A, and oxytocin infused here was anxiolytic but had no effect on female sex behavior. Therefore, we have identified brain region-specific regulation of the OTR in the VMH and cAmyg. Distinct signal transduction pathways regulating receptor expression and binding in each brain region may mediate in part the ability of oxytocin to exert these differential behavioral effects.

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Section: Discussionmentioning

confidence: 99%

CNS Region-Specific Oxytocin Receptor Expression: Importance in Regulation of Anxiety and Sex Behavior

et al. 2001

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“…Classical ERs targeted to the plasma membrane associate with caveolin and regulate phosphorylation of proteins in the MAPK and ERK signaling pathways (3)(4)(5)(6)(7)(8)(9)(10)(11). In terms of sexual receptivity, blocking kinase activity attenuates lordosis behavior in rodents, which emphasizes the role of second messengers in addition to transcriptional effects (12,13).…”

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confidence: 97%

Protein Kinase C Signaling in the Hypothalamic Arcuate Nucleus Regulates Sexual Receptivity in Female Rats

et al. 2008

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Rapid membrane-mediated estradiol signaling regulating sexual receptivity requires the interaction of the estrogen receptor (ER)-alpha and the metabotropic glutamate receptor 1a (mGluR1a). A cell signaling antibody microarray revealed that estradiol activated 42 proteins in the arcuate nucleus of the hypothalamus (ARH). To begin an analysis of various signaling pathways, protein kinase A and protein kinase C (PKC)-theta, whose signaling pathways have been implicated in the estradiol regulation of sexual receptivity, were examined. In the ARH sample, the increase in phospho-protein kinase A could not be confirmed by Western blotting, in either cytosolic or membrane fractions. However, the increase in phosphorylated PKCtheta seen with the pathway array was verified by Western blotting. To study whether rapid estradiol activation of PKC regulates the ARH-medial preoptic nucleus pathway regulating lordosis, mu-opioid receptor (MOR) internalization and lordosis reflex were tested. Blocking PKC in ARH with 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]3-(1H-indol-3-yl) maleimide significantly attenuated estradiol-induced MOR internalization. Furthermore, disruption of PKC signaling within the ARH at the time of estradiol treatment significantly diminished the lordosis reflex. Moreover, blocking PKC prevented MOR internalization when the circuit was activated by the mGluR1a agonist, (RS)-3,5-dihydroxyphenylglycine. Activation of PKC with phorbol 12, 13-dibutyrate induced MOR internalization, indicating that PKC was a critical step for membrane ERalpha-initiated mGluR1a-mediated cell signaling and phorbol 12, 13-dibutyrate significantly facilitated the lordosis reflex. Together these findings indicate that rapid membrane ERalpha-mGluR1a interactions activate PKCtheta cell signaling, which regulates female sexual receptivity.

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“…The present findings also suggest that progesterone's actions on lordosis may include modulation of the classic D 1 ‐initiated intracellular signalling cascade that leads to up‐regulation of cAMP. Activation of D 1 is known to lead to recruitment of Gα s and increases in cAMP (42). Previous reports from our laboratory show that, in the VTA, activating D 1 enhances and antagonising D 1 reduces progestin‐facilitated lordosis (14–18).…”

Section: Discussionmentioning

confidence: 99%

In the Ventral Tegmental Area, Cyclic AMP Mediates the Actions of Progesterone at Dopamine Type 1 Receptors for Lordosis of Rats and Hamsters

Petralia¹,

Frye

2006

J Neuroendocrinology

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Progesterone-facilitated lordosis is enhanced by activation of, and inhibited by antagonism of, dopamine type 1 receptors (D1) in the ventral tegmental area (VTA). Given that D1 activation leads to increases in cyclic AMP (cAMP), we hypothesised that, in the VTA, progesterone's actions on lordosis that involve D1 are mediated, in part, by cAMP. In Experiment 1, naturally receptive rats and hamsters were pretested for lordosis, infused with the cAMP analogue 8-bromo-cAMP (200 ng) or vehicle to the VTA, and tested again 30 min later. In Experiments 2 and 3, ovariectomised, oestradiol (10 microg) + progesterone (0 or 100 microg)-primed rats and oestradiol (10 microg) + progesterone (0 or 200 microg)-primed hamsters were pretested for lordosis and infused with 8-bromo-cAMP (200 ng), the adenylyl cyclase inhibitor 2',5'-dideoxyadenosine (12 microM) or vehicle to the VTA. Subjects were tested again 30 min later. In Experiment 4, oestradiol + progesterone-primed rats and hamsters were pretested and infused with the D1 agonist SKF38393 (0 or 100 ng) to the VTA. Thirty minutes later, subjects were tested again and infused with 2',5'-dideoxyadenosine (12 microM) or vehicle. Subjects were tested again 30 min later. VTA infusions of 8-bromo-cAMP enhanced lordosis of naturally receptive or hormone-primed rats and hamsters and 2',5'-dideoxyadenosine decreased lordosis of oestradiol + progesterone-primed rats and hamsters. D1-mediated increases in progesterone-facilitated lordosis were reduced by 2',5'-dideoxyadenosine. These data suggest that progesterone-facilitated lordosis of rats and hamsters may be modulated by D1 and cAMP activity in the VTA.

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Phorbol esters and forskolin infused into midbrain central gray facilitate lordosis

Cited by 27 publications

References 0 publications

CNS Region-Specific Oxytocin Receptor Expression: Importance in Regulation of Anxiety and Sex Behavior

CNS Region-Specific Oxytocin Receptor Expression: Importance in Regulation of Anxiety and Sex Behavior

Protein Kinase C Signaling in the Hypothalamic Arcuate Nucleus Regulates Sexual Receptivity in Female Rats

In the Ventral Tegmental Area, Cyclic AMP Mediates the Actions of Progesterone at Dopamine Type 1 Receptors for Lordosis of Rats and Hamsters

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