Actions of Peripubertal Gonadal Steroids in the Formation of Sexually Dimorphic Brain Regions in Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (6) ◽  
Author(s):  
Masahiro Morishita ◽  
Ryoma Koiso ◽  
Shinji Tsukahara
Keyword(s):  
Sex Differences ◽  
Immunohistochemical Analysis ◽  
Brain Regions ◽  
Sexually Dimorphic ◽  
Stria Terminalis ◽  
Neuron Number ◽  
Bed Nucleus ◽  
Action Mechanisms ◽  
Sexually Dimorphic Nucleus ◽  
Immunohistochemical Analyses

Abstract The calbindin-sexually dimorphic nucleus (CALB-SDN) and calbindin-principal nucleus of the bed nucleus of the stria terminalis (CALB-BNSTp) show male-biased sex differences in calbindin neuron number. The ventral part of the BNSTp (BNSTpv) exhibits female-biased sex differences in noncalbindin neuron number. We previously reported that prepubertal gonadectomy disrupts the masculinization of the CALB-SDN and CALB-BNSTp and the feminization of the BNSTpv. This study aimed to determine the action mechanisms of testicular androgens on the masculinization of the CALB-SDN and CALB-BNSTp and whether ovarian estrogens are the hormones that have significant actions in the feminization of the BNSTpv. We performed immunohistochemical analyses of calbindin and NeuN, a neuron marker, in male mice orchidectomized on postnatal day 20 (PD20) and treated with cholesterol, testosterone, estradiol, or dihydrotestosterone during PD20-70, female mice ovariectomized on PD20 and treated with cholesterol or estradiol during PD20-70, and PD70 mice gonadectomized on PD56. Calbindin neurons number in the CALB-SDN and CALB-BNSTp in males treated with testosterone or dihydrotestosterone, but not estradiol, was significantly larger than that in cholesterol-treated males. Noncalbindin neuron number in the BNSTpv in estradiol-treated females was significantly larger than that in cholesterol-treated females. Gonadectomy on PD56 had no significant effect on neuron numbers. Additionally, an immunohistochemical analysis revealed the expression of androgen receptors in the CALB-SDN and CALB-BNSTp of PD30 males and estrogen receptors-α in the BNSTpv of PD30 females. These results suggest that peripubertal testicular androgens act to masculinize the CALB-SDN and CALB-BNSTp without aromatization, and peripubertal ovarian estrogens act to feminize the BNSTpv.

scholarly journals Epigenetic Control of Sexual Differentiation of the Bed Nucleus of the Stria Terminalis

Endocrinology ◽  
2009 ◽  
Vol 150 (9) ◽  
pp. 4241-4247 ◽  
Author(s):  
Elaine K. Murray ◽  
Annie Hien ◽  
Geert J. de Vries ◽  
Nancy G. Forger
Keyword(s):  
Cell Death ◽  
Sex Differences ◽  
Sexual Differentiation ◽  
Cell Number ◽  
Histone Deacetylation ◽  
Postnatal Life ◽  
Sexually Dimorphic ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Deacetylase Inhibitor

Abstract The principal nucleus of the bed nucleus of the stria terminalis (BNSTp) is larger in volume and contains more cells in male than female mice. These sex differences depend on testosterone and arise from a higher rate of cell death during early postnatal life in females. There is a delay of several days between the testosterone surge at birth and sexually dimorphic cell death in the BNSTp, suggesting that epigenetic mechanisms may be involved. We tested the hypothesis that chromatin remodeling plays a role in sexual differentiation of the BNSTp by manipulating the balance between histone acetylation and deacetylation using a histone deacetylase inhibitor. In the first experiment, a single injection of valproic acid (VPA) on the day of birth increased acetylation of histone H3 in the brain 24 h later. Next, males, females, and females treated neonatally with testosterone were administered VPA or saline on postnatal d 1 and 2 and killed at 21 d of age. VPA treatment did not influence volume or cell number of the BNSTp in control females but significantly reduced both parameters in males and testosterone-treated females. As a result, the sex differences were eliminated. VPA did not affect volume or cell number in the suprachiasmatic nucleus or the anterodorsal nucleus of the thalamus, which also did not differ between males and females. These findings suggest that a disruption in histone deacetylation may lead to long-term alterations in gene expression that block the masculinizing actions of testosterone in the BNSTp.

scholarly journals Microarray analysis reveals distinctive signaling between the bed nucleus of the stria terminalis, nucleus accumbens, and dorsal striatum

2008 ◽  
Vol 32 (3) ◽  
pp. 283-298 ◽  
Author(s):  
Christopher M. Olsen ◽  
Yong Huang ◽  
Shirlean Goodwin ◽  
Daniel C. Ciobanu ◽  
Lu Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Synaptic Plasticity ◽  
Nucleus Accumbens ◽  
Signaling Pathways ◽  
Microarray Analysis ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Insight Into

To identify distinct transcriptional patterns between the major subcortical dopamine targets commonly studied in addiction we studied differences in gene expression between the bed nucleus of the stria terminalis (BNST), nucleus accumbens (NAc), and dorsal striatum (dStr) using microarray analysis. We first tested for differences in expression of genes encoding transcripts for common neurotransmitter systems as well as calcium binding proteins routinely used in neuroanatomical delineation of brain regions. This a priori method revealed differential expression of corticotropin releasing hormone ( Crh), the GABA transporter ( Slc6a1), and prodynorphin ( Pdyn) mRNAs as well as several others. Using a gene ontology tool, functional scoring analysis, and Ingenuity Pathway Analysis, we further identified several physiological pathways that were distinct among these brain regions. These two different analyses both identified calcium signaling, G-coupled protein receptor signaling, and adenylate cyclase-related signaling as significantly different among the BNST, NAc, and dStr. These types of signaling pathways play important roles in, amongst other things, synaptic plasticity. Investigation of differential gene expression revealed several instances that may provide insight into reported differences in synaptic plasticity between these brain regions. The results support other studies suggesting that crucial pathways involved in neurotransmission are distinct among the BNST, NAc, and dStr and provide insight into the potential use of pharmacological agents that may target region-specific signaling pathways. Furthermore, these studies provide a framework for future mouse-mouse comparisons of transcriptional profiles after behavioral/pharmacological manipulation.

scholarly journals Evidence of Altered Brain Sexual Differentiation in Mice Exposed Perinatally to Low, Environmentally Relevant Levels of Bisphenol A

Endocrinology ◽  
2006 ◽  
Vol 147 (8) ◽  
pp. 3681-3691 ◽  
Author(s):  
Beverly S. Rubin ◽  
Jenny R. Lenkowski ◽  
Cheryl M. Schaeberle ◽  
Laura N. Vandenberg ◽  
Paul M. Ronsheim ◽  
...  
Keyword(s):  
Sex Differences ◽  
Bisphenol A ◽  
Brain Development ◽  
Sexual Differentiation ◽  
Female Offspring ◽  
Sexually Dimorphic ◽  
Critical Periods ◽  
Neuron Number ◽  
Brain Sexual Differentiation ◽  
Estrogenic Chemical

Humans are routinely exposed to bisphenol A (BPA), an estrogenic chemical present in food and beverage containers, dental composites, and many products in the home and workplace. BPA binds both classical nuclear estrogen receptors and facilitates membrane-initiated estrogenic effects. Here we explore the ability of environmentally relevant exposure to BPA to affect anatomical and functional measures of brain development and sexual differentiation. Anatomical evidence of alterations in brain sexual differentiation were examined in male and female offspring born to mouse dams exposed to 0, 25, or 250 ng BPA/kg body weight per day from the evening of d 8 of gestation through d 16 of lactation. These studies examined the sexually dimorphic population of tyrosine hydroxylase (TH) neurons in the rostral periventricular preoptic area, an important brain region for estrous cyclicity and estrogen-positive feedback. The significant sex differences in TH neuron number observed in control offspring were diminished or obliterated in offspring exposed to BPA primarily because of a decline in TH neuron number in BPA-exposed females. As a functional endpoint of BPA action on brain sexual differentiation, we examined the effects of perinatal BPA exposure on sexually dimorphic behaviors in the open field. Data from these studies revealed significant sex differences in the vehicle-exposed offspring that were not observed in the BPA-exposed offspring. These data indicate that BPA may be capable of altering important events during critical periods of brain development.

Sign in / Sign up

Export Citation Format

Share Document