Estrogen receptor alpha is required in GABAergic, but not glutamatergic, neurons to masculinize the brain.

Wu, Melody, Tollkuhn, Jessica (March 2017) Estrogen receptor alpha is required in GABAergic, but not glutamatergic, neurons to masculinize the brain. BioRxiv. (Unpublished)

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DOI: 10.1101/114835


Abstract Masculinization of the rodent brain is driven by estrogen signaling during a perinatal critical period. Genetic deletion of estrogen receptor alpha ( Esr1/ ERα) results in altered hypothalamic-pituitary-gonadal (HPG) axis signaling and a dramatic reduction of male sexual and territorial behaviors. However, the requirement of ERα function in masculinizing distinct classes of neurons, and if these populations mediate components of male-typical behavior, remains unexplored. We deleted ERα in excitatory or inhibitory neurons using either a Vglut2 or Vgat driver and assessed male behaviors. We find that Vglut2 -Cre; Esr1 lox/lox mutant males lack ERa in the ventrolateral region of the ventromedial hypothalamus (VMHvl) and posterior ventral portion of the medial amygdala (MePV). These mutants recapitulate the increased serum testosterone levels seen with constitutive ERα deletion, but have none of the behavioral deficits. In contrast, Vgat -Cre; Esr1 lox/lox males with substantial ERα deletion in inhibitory neurons, including those of the principal nucleus of the bed nucleus of the stria terminalis (BNSTpr), posterior dorsal MeA (MePD), and medial preoptic area (MPOA) have normal testosterone levels, but display alterations in mating and territorial behaviors. These mutants also show demasculinized expression of androgen receptor (AR) and estrogen receptor beta (Esr2). Our results demonstrate that ERα masculinizes GABAergic neurons that gate the display of male-typical behaviors.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > small molecules > estrogen
organism description > animal behavior > sex differences
bioinformatics > genomics and proteomics > small molecules > testosterone
CSHL Authors:
Communities: CSHL labs > Tollkuhn lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 7 March 2017
Date Deposited: 10 May 2021 13:41
Last Modified: 10 May 2021 13:41

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