Role of estrogen receptor α and β in the induction of progesterone receptors in hypothalamic ventromedial neurons

Sá, Susana I.; Pereira, Pedro; Malikov, Viacheslav; Madeira, M. Dulce

doi:10.1016/j.neuroscience.2013.02.023

Cited by 24 publications

(28 citation statements)

References 56 publications

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“…This effect is not accompanied by a commensurate variation in the quantity of PRs in the cytoplasm, leading to a high nuclear/cytoplasmic ratio of PR expression. Also in line with previous studies that have estimated PR mRNA levels and total numbers of PR‐immunoreactive neurons in the VMNvl, the administration of the selective ERα agonist increased the amount of PR protein in the VMNvl nuclear fraction. However, and in contrast to EB, there were no changes in the intensity of PR immunoreactivity in individual neuronal nuclei after PPT administration.…”

Section: Discussionsupporting

confidence: 90%

“…We and others have previously shown that the administration of estrogens to ovariectomized rats increases PR mRNA and protein levels and the total number of PR‐immunoreactive neurons in the VMNvl . The present study complements and extends these observations by showing that the EB‐induced increase in the quantity of PR protein in the VMNvl is also attributable to an increase in the PR content of individual neuronal nuclei.…”

Section: Discussionsupporting

confidence: 86%

“…The activation of the ERα subtype by its specific agonist propyl‐pyrazole triol (PPT) induces the expression of PRs and increases the number of PR‐immunoreactive neurons in the VMNvl , enhances proceptive behaviors, and increases lordosis quotients . None of these effects has been reproduced by activation of the ERβ subtype , which, in contrast to ERα activation, promotes high rejection quotients both in ER knockout mice and in rats injected with the ERβ‐specific agonist diaryl‐propionitrile (DPN) . There is also evidence that ERβ can modulate ERα activity in a dose‐dependent manner and regulate ERα‐mediated gene transcription .…”

Section: Introductionmentioning

confidence: 99%

“…There is also evidence that ERβ can modulate ERα activity in a dose‐dependent manner and regulate ERα‐mediated gene transcription . Specifically, the simultaneous activation of ERα and ERβ by their respective agonists prevents the ERα‐induced increase in the number of PR‐immunoreactive neurons in the VMNvl , but, paradoxically, triggers lordosis quotients that, however, are inconstant and of relatively low amplitude . In addition, it was recently shown that, in cultured VMNvl neurons, the simultaneous activation of ERα and ERβ by their agonists increases the expression of ERα in VMNvl neurons , which would lead to the promotion of ERα‐mediated PR expression in the VMNvl and increased lordotic responses.…”

Section: Introductionmentioning

confidence: 99%

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Estrogen receptors α and β have different roles in the induction and trafficking of progesterone receptors in hypothalamic ventromedial neurons

et al. 2015

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Progesterone receptor (PR) activation in the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) is essential for promoting female sexual behavior. Estrogen receptor (ER) a, in contrast to ERb, has been implicated in the induction of PRs. The simultaneous activation of ERa and ERb, although not increasing the number of PR-immunoreactive neurons in the VMNvl, facilitates lordosis, which suggests that ERb and/or the ERa-ERb interaction might play a role in PR dynamics and/or PR expression by individual neurons. To address this question, we used western blot and immunohistochemical studies to determine the amounts and subcellular distributions of both PR isoforms in VMNvl neurons of ovariectomized rats injected with estradiol benzoate or with specific agonists of ERa and ERb, alone or in association. The present data show that ERa activation does not change PR expression in individual neurons, but increases the number of PRs in the VMNvl, because it increases the number of neurons expressing PRs. Conversely, ERb activation does not change the total number of PRs in the VMNvl, but increases the labeling intensity of the perikaryal cytoplasm, which suggests that it promotes the transport of PRs from neurites into cell bodies. In addition, the simultaneous activation of ERa and ERb increases the expression of PRs by individual neurons and, consequently, increases the total number of PRs in the VMNvl. Our findings reveal that individual and simultaneous activation of ERa and ERb have different effects on the levels and subcellular location of PRs in VMNvl neurons. IntroductionEndogenous progesterone plays a critical role in the regulation of female reproductive functions, including sexual behavior. By acting through its cognate receptors, progesterone modulates sexual behavior [1][2][3] and, according to the phase of the estrous cycle, activates or inhibits the sexual response [4][5][6]. These actions require previous estrogen priming [7,8] for the induction of progesterone receptors (PRs) in the brain areas that are involved in the modulation of sexual behavior [8][9][10]. This is the case for the hypothalamic ventromedial nucleus (VMN), particularly its ventrolateral division (VMNvl). Neurons located in this divi-0 ,6-diamidino-2-phenylindole; DPN, diaryl-propionitrile; EB, estradiol benzoate; ER, estrogen receptor; PPT, propyl-pyrazole triol; PR, progesterone receptor; VMN, hypothalamic ventromedial nucleus; VMNvl, ventrolateral division of the hypothalamic ventromedial nucleus.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Estrogen receptors α and β have different roles in the induction and trafficking of progesterone receptors in hypothalamic ventromedial neurons

et al. 2015

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“…We hypothesize that these examples reflect the actions of estradiol through ERβ. While our findings from the current study do not directly support the hypothesis that ERβ activation promotes prosocial behavior, our negative findings in E2-treated voles might suggest that ERβ activation can counteract the negative effects of ERα activation on prosocial behavior and aggression- consistent with numerous other studies demonstrating an antagonistic relationship between ERα and ERβ (Mazzucco et al, 2008; SÃ et al, 2013; Song and Pan, 2012). However, future studies will need to directly address this possibility by treating subjects with combinations of PPT and DPN, or with E2 in conjunction with selective antagonists (Santollo et al, 2010).…”

Section: Discussionsupporting

confidence: 69%

Effects of postnatal estrogen manipulations on juvenile alloparental behavior

Perry

Carter

Cushing

2015

Hormones and Behavior

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Sex- and species-specific patterns of estrogen receptor (ER)-α expression are established early in development, which may contribute to sexual differentiation of behavior and determine male social organization. The current study investigated the effects of ERα and ERβ activation during the second postnatal week on subsequent alloparental behavior and ERα expression in juvenile prairie voles. Male and female pups were treated daily with 17β-estradiol (E2, ERα/ERβ agonist), PPT (selective ERα agonist), DPN (selective ERβ agonist), or the oil vehicle on postnatal days (PD) 8-14. Alloparental behavior and ERα expression were examined at PD21. PPT treatment inhibited prosocial motivation in males and increased pup-directed aggression in both sexes. E2 and DPN had no apparent effect on behavior in either sex. PPT-treated males had increased ERα expression in the medial preoptic area (MPN), medial amygdala (MEApd) and bed nucleus of the stria terminalis (BSTpr). DPN treatment also increased ERα expression in males, but only in the BSTpr. Female ERα expression was unaffected by treatment. These results support the hypothesis that ERα activation in early life is associated with less prosocial patterns of central ERα expression and alloparental behavior in males. The lack of an effect of E2 on behavior suggests that ERβ may antagonize the effects of ERα on alloparental behavior. The results in DPN-treated males suggest that ERα in the MEApd, and not the BSTpr, may be a primary determinant of alloparental behavior in males.

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Role of plasma membrane estrogen receptors in mediating the estrogen induction of progesterone receptors in hypothalamic ventromedial neurons

Sá

Pereira

Malikov

et al. 2013

J of Comparative Neurology

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Progesterone is well known for its role in the modulation of sexual behavior. In the ventromedial nucleus (VMN), a part of the mediobasal hypothalamus that regulates sexual behavior in female rodents, estrogens induce the expression of progesterone receptors (PRs). This effect is known to be dependent on the activation of nuclear estrogen receptors (ERs). However, recent studies have documented estrogen activation of genomic transcription triggered by protein-protein phosphorylation cascades initiated at membrane receptors. The aim of this study was to examine if membrane-initiated estradiol (E2 ) stimulation is able to induce PR expression in the VMN or, at least, to modulate nuclear ER action. To achieve this goal, 2-month-old ovariectomized Wistar rats were injected bilaterally, in the vicinity of VMN, with free E2 and with E2 conjugated with bovine serum albumin (E2 BSA), alone or in sequence, by using a two-pulse injection paradigm. Stereological methods and western blot analysis were used to estimate the total number of PR-immunoreactive neurons in the VMN and the PR protein content of the VMN, respectively. The results showed that the administration of E2 BSA alone increases the number of PR-immunoreactive neurons and the expression level of PR protein to values similar to those resulting from E2 administration. They also showed that the sequential administration of E2 and E2 BSA potentiates the effects resulting from the injection of E2 or E2 BSA alone. These data provide the first evidence that membrane-initiated E2 stimulation is able to induce and to potentiate the genomic activation of PR expression in the VMN.

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Role of estrogen receptor α and β in the induction of progesterone receptors in hypothalamic ventromedial neurons

Cited by 24 publications

References 56 publications

Estrogen receptors α and β have different roles in the induction and trafficking of progesterone receptors in hypothalamic ventromedial neurons

Estrogen receptors α and β have different roles in the induction and trafficking of progesterone receptors in hypothalamic ventromedial neurons

Effects of postnatal estrogen manipulations on juvenile alloparental behavior

Role of plasma membrane estrogen receptors in mediating the estrogen induction of progesterone receptors in hypothalamic ventromedial neurons

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