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Estradiol Preferentially Induces Progestin Receptor-A (PR-A) Over PR-B in Cells Expressing Nuclear Receptor Coactivators in the Female Mouse Hypothalamus(1,2,3).

Acharya KD, Finkelstein SD, Bless EP, Nettles SA, Mulac-Jericevic B, Conneely OM, Mani SK, Tetel MJ - eNeuro (2015)

Bottom Line: Estrogens act in brain to profoundly influence neurogenesis, sexual differentiation, neuroprotection, cognition, energy homeostasis, and female reproductive behavior and physiology through a variety of mechanisms, including the induction of progestin receptors (PRs).Interestingly, the intensity of PR-A immunoreactivity correlated with SRC-2 expression in the VMN, providing a potential mechanism for selective ER-mediated transactivation of PR-A over PR-B in a brain region-specific manner.In summary, these novel findings indicate that estrogens differentially regulate PR-A and PR-B expression in the female hypothalamus, and provide a mechanism by which steroid action in brain can selectively modulate behavior and physiology.

View Article: PubMed Central - HTML - PubMed

Affiliation: Neuroscience Program, Wellesley College , Wellesley, Massachusetts 02481.

ABSTRACT
Estrogens act in brain to profoundly influence neurogenesis, sexual differentiation, neuroprotection, cognition, energy homeostasis, and female reproductive behavior and physiology through a variety of mechanisms, including the induction of progestin receptors (PRs). PRs are expressed as two isoforms, PR-A and PR-B, that have distinct functions in physiology and behavior. Because these PR isoforms cannot be distinguished using cellular resolution techniques, the present study used isoform-specific mutant mice that lack PR-A or PR-B for the first time to investigate whether 17β-estradiol benzoate (EB) regulates the differential expression of the PR isoforms in the ventromedial nucleus of the hypothalamus (VMN), arcuate nucleus, and medial preoptic area, brain regions that are rich in EB-induced PRs. Interestingly, EB induced more PR-A than PR-B in all three brain regions, suggesting that PR-A is the predominant isoform in these regions. Given that steroid receptor coactivator (SRC)-1 and SRC-2 are important in estrogen receptor (ER)-dependent transcription in brain, including PR induction, we tested whether the expression of these coactivators was correlated with PR isoform expression. The majority of EB-induced PR cells expressed both SRC-1 and SRC-2 in the three brain regions of all genotypes. Interestingly, the intensity of PR-A immunoreactivity correlated with SRC-2 expression in the VMN, providing a potential mechanism for selective ER-mediated transactivation of PR-A over PR-B in a brain region-specific manner. In summary, these novel findings indicate that estrogens differentially regulate PR-A and PR-B expression in the female hypothalamus, and provide a mechanism by which steroid action in brain can selectively modulate behavior and physiology.

No MeSH data available.


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A–C, Immunostaining intensity of estradiol-induced PR is greater in wt mice than in PRAKO mice in the VMN (A), but not in the ARC (B) or MPA (C). *p < 0.05.
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Figure 3: A–C, Immunostaining intensity of estradiol-induced PR is greater in wt mice than in PRAKO mice in the VMN (A), but not in the ARC (B) or MPA (C). *p < 0.05.

Mentions: To investigate whether there was a difference between the relative amounts of PR-A and PR-B immunoreactive intensity, we examined the mean PR-ir intensity within cells in the VMN, ARC, and MPA of EB-treated wt, PRAKO, and PRBKO mice. In the VMN, mean PR-ir intensity was stronger in wt mice than in PRAKO mice (F(2,29) = 6.265, p = 0.006; Fig. 3A). In the ARC and MPA, no differences were detected between genotypes (Fig. 3B,C).


Estradiol Preferentially Induces Progestin Receptor-A (PR-A) Over PR-B in Cells Expressing Nuclear Receptor Coactivators in the Female Mouse Hypothalamus(1,2,3).

Acharya KD, Finkelstein SD, Bless EP, Nettles SA, Mulac-Jericevic B, Conneely OM, Mani SK, Tetel MJ - eNeuro (2015)

A–C, Immunostaining intensity of estradiol-induced PR is greater in wt mice than in PRAKO mice in the VMN (A), but not in the ARC (B) or MPA (C). *p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4596027&req=5

Figure 3: A–C, Immunostaining intensity of estradiol-induced PR is greater in wt mice than in PRAKO mice in the VMN (A), but not in the ARC (B) or MPA (C). *p < 0.05.
Mentions: To investigate whether there was a difference between the relative amounts of PR-A and PR-B immunoreactive intensity, we examined the mean PR-ir intensity within cells in the VMN, ARC, and MPA of EB-treated wt, PRAKO, and PRBKO mice. In the VMN, mean PR-ir intensity was stronger in wt mice than in PRAKO mice (F(2,29) = 6.265, p = 0.006; Fig. 3A). In the ARC and MPA, no differences were detected between genotypes (Fig. 3B,C).

Bottom Line: Estrogens act in brain to profoundly influence neurogenesis, sexual differentiation, neuroprotection, cognition, energy homeostasis, and female reproductive behavior and physiology through a variety of mechanisms, including the induction of progestin receptors (PRs).Interestingly, the intensity of PR-A immunoreactivity correlated with SRC-2 expression in the VMN, providing a potential mechanism for selective ER-mediated transactivation of PR-A over PR-B in a brain region-specific manner.In summary, these novel findings indicate that estrogens differentially regulate PR-A and PR-B expression in the female hypothalamus, and provide a mechanism by which steroid action in brain can selectively modulate behavior and physiology.

View Article: PubMed Central - HTML - PubMed

Affiliation: Neuroscience Program, Wellesley College , Wellesley, Massachusetts 02481.

ABSTRACT
Estrogens act in brain to profoundly influence neurogenesis, sexual differentiation, neuroprotection, cognition, energy homeostasis, and female reproductive behavior and physiology through a variety of mechanisms, including the induction of progestin receptors (PRs). PRs are expressed as two isoforms, PR-A and PR-B, that have distinct functions in physiology and behavior. Because these PR isoforms cannot be distinguished using cellular resolution techniques, the present study used isoform-specific mutant mice that lack PR-A or PR-B for the first time to investigate whether 17β-estradiol benzoate (EB) regulates the differential expression of the PR isoforms in the ventromedial nucleus of the hypothalamus (VMN), arcuate nucleus, and medial preoptic area, brain regions that are rich in EB-induced PRs. Interestingly, EB induced more PR-A than PR-B in all three brain regions, suggesting that PR-A is the predominant isoform in these regions. Given that steroid receptor coactivator (SRC)-1 and SRC-2 are important in estrogen receptor (ER)-dependent transcription in brain, including PR induction, we tested whether the expression of these coactivators was correlated with PR isoform expression. The majority of EB-induced PR cells expressed both SRC-1 and SRC-2 in the three brain regions of all genotypes. Interestingly, the intensity of PR-A immunoreactivity correlated with SRC-2 expression in the VMN, providing a potential mechanism for selective ER-mediated transactivation of PR-A over PR-B in a brain region-specific manner. In summary, these novel findings indicate that estrogens differentially regulate PR-A and PR-B expression in the female hypothalamus, and provide a mechanism by which steroid action in brain can selectively modulate behavior and physiology.

No MeSH data available.


Related in: MedlinePlus