Sex and estrogenic effects on coexpression of mRNAs in single ventromedial hypothalamic neurons

Abstract

(102, 14446-14451; first published September 26, 2005; 10.1073͞pnas.0507144102), the authors note that ''%'' was added after several numbers, due to a printer's error. On page 14449, right column, the second sentence under Estrogen Treatment Increases Number of ER␣, ER␤, OTR, and PKCs in Female Rats, ''In estrogen-treated animals, these numbers were higher than in the oil group, ER␣ (66% vs. 20%), ER␤ (39% vs. 14%), OTR (56% vs. 15%), PKC␦ (28% vs. 8%), PKC (30% vs. 8%), and PKC (44% vs. 12%) (P Ͻ 0.05 in all cases) (Tables 3 and 4),'' should read: ''In estrogen-treated animals, these numbers were higher than in the oil group, ER␣ (66 vs. 20 estrogen ͉ hypothalamus ͉ lordosis ͉ oxytocin ͉ PKC E strogens, steroid sex hormones, play important roles in the development and establishment of reproductive and sexual behaviors as well as many other nonreproductive functions (1-4). Although estrogens' actions in females are relatively well understood, its role in male CNS function is less studied (5). Estrogens are regulated by binding to specific nuclear estrogen receptors (ERs), ER␣ and ER␤, ligand-activated transcription factors (6). ER␣ and ER␤ belong to a large group of six subfamilies of transcription factors (7), one of which comprises the steroid receptors (8). ER expression in the brain varies by region (9) and can affect both female and male sexual behaviors (10-12). Both ER␣ and ER␤ are expressed in the hypothalamus, and particularly in ventromedial nucleus (VMN), which is well known to regulate female sexual behavior (13,14).In addition to regulating sexual behaviors, estrogens affect affiliative social behaviors by affecting mRNA levels for the oxytocin receptors (OTR) (15), which are expressed in VMN (4,(16)(17)(18)(19). Regulation of OTR by estrogens in VMN has been shown in females as well as males (16,18,(20)(21)(22)(23)(24)(25). A four-gene micronet theory featuring ER␣, ER␤, oxytocin, and OTR and has been proposed to explain how neurons in hypothalamus and amygdala cooperate to facilitate social behaviors in female rodents (26,27). OTRs are important for sex and anxiety behaviors (4). Regulation of OTR also requires second messenger-mediated kinases (28), one of which involves PKCs (29). Evidence shows that PKC␣ associates with OTR within 2 min of agonist stimulation (30).It has been demonstrated that estrogens have two types of actions: genomic and membrane (31-33). Although ERs play a major role in genomic actions of estrogens, nongenomic actions in neurons involve several signal transduction pathways (34). And although lordosis behavior requires genomic actions of estrogens in VMN (35), estrogen-induced membrane actions in VMN can potentiate these genomic actions in a manner involving PKC (14). Several in vitro studies show that activation of PKC is involved in the potentiating effect of the rapid membrane actions of estrogens (34,(36)(37)(38)(39). PKCs comprise a family of 12 related isozymes (40) that are divided into three groups: classical or calcium-dependent (PKC␣, -␤I, -␤II, and -␥); the n...

Androgen receptors are required for full masculinization of the ventromedial hypothalamus (VMH) in rats

“…The VMHvl and VMHdm are both targets for gonadal steroids, but differ in the proportion of cells expressing ER and AR mRNA (Simerly et al, 1990;Devidze, et al, 2005). Data from the current study suggest that VMHvl and VMHdm volume may underlie some of these sex differences in function, since they are sexually dimorphic in this regard.…”

The Meaning of Weaning: Influence of the Weaning Period on Behavioral Development in Mice

“…In males, the VMH is critical in the regulation of sexual and aggressive behaviors primarily through the actions of estrogen on ER ␣ [Harding and McGinnis, 2004;Nelson and Trainor, 2007]. OT receptor expression in the VMH is up-regulated following increases in estradiol [Bale et al, 2001] or decreases in progesterone [Windle et al, 2006], and estrogen and oxytocin receptor mRNA is found to be co-expressed in VMH neurons [Devidze et al, 2005]. Taken together with our data, these findings suggest that variation in maternal care across the whole of the postnatal period can induce changes in offspring reproductive strategies.…”

Hormone Effects on Specific and Global Brain Functions

“…Doing this, Devidze et al [36] found that the population of VMN neurons expressing ER-alpha was different from those expressing its likely gene duplication product ER-beta, and that an extremely high proportion of neurons expressing either ER also coexpresses mRNA for the oxytocin receptor. Patterns of triple coexpression among ERs, OTR, and each selected PKC isoform were signifi cantly different between female and male.…”

“…A new way of studying estrogenic effects on gene expression in the brain is to use micropipettes to suck the mRNA contents from individual nerve cells to study the coexpression of genes in single neurons [36]. Doing this, Devidze et al [36] found that the population of VMN neurons expressing ER-alpha was different from those expressing its likely gene duplication product ER-beta, and that an extremely high proportion of neurons expressing either ER also coexpresses mRNA for the oxytocin receptor.…”