17β-estradiol upregulates oxytocin and the oxytocin receptor in C2C12 myotubes
Keywords: estradiol, oxytocin, hypothalamus, pituitary, adrenal, behavior, anxiety . Additionally, OT signaling differs between males and females. . of any commercial or financial relationships that could be construed as a. Oxytocin (Oxt) is a peptide hormone and neuropeptide. Oxytocin is normally produced by the . Estrogen has been found to increase the secretion of oxytocin and to .. Sexual activity: The relationship between oxytocin and human sexual. Effects of RU on Estrogen, Progesterone, Oxytocin, and Their Receptors in the Rat .. Significant difference between the RU and control groups, using.
OT binds to the widely expressed OT receptor OTRand, in doing so, it regulates homeostatic processes, social recognition, and fear conditioning. In addition to these functions, OT decreases neuroendocrine stress signaling and anxiety-related and depression-like behaviors.
Steroid hormones differentially modulate stress responses and alter OTR expression. Further research is needed to identify modulators of OT signaling and the pathways utilized and to elucidate molecular mechanisms controlling OT expression to allow better therapeutic manipulations of this system in patient populations.
Ask the Experts: Jennie Stevenson discusses the hormone oxytocin
OT is produced primarily in the neurons of the hypothalamic paraventricular nucleus PVN and supraoptic nucleus [SON 2 ], is released into systemic circulation, and plays an important role in lactation, parturition, maternal behavior, and pair-bond formation 34. Additionally, OT is released from the PVN axon terminals that project throughout the brain into regions, such as the hippocampus, striatum, and amygdala 5and has been implicated in the regulation of memory, stress, and social behaviors 1.
In addition to traditional release across a synapse, OT is also released from neuron somas and dendrites and can reach nearby brain regions via volume transmission by diffusing across neural tissue 6.
In this review, we focus on the function of OT in the brain and its modulation by estrogens.
Oxytocin and Estrogen Receptor β in the Brain: An Overview
Autoradiographic studies have identified OTR expression in several regions of the rat brain, including the olfactory system, basal ganglia, hippocampus, central amygdala, and hypothalamus 7. The generation of a knock-in mouse strain where Venus, a variant of yellow fluorescent protein, is under the regulation of the Otr promoter sequence, facilitated the identification of OTR expressing cells in additional brain regions, e.
This mouse model has been valuable in the identification of the phenotype of the cells expressing OTRs. For instance, OTRs have been found in serotonergic neurons 8implicating serotonergic involvement in OTs anxiolytic effects in depression and anxiety. Central OT is important in homeostatic processes, such as thermoregulation 9food intake 10and mating 11 OT also plays an important role in maternal behavior.
Additionally, central administration of an OTR antagonist OTA completely eliminated the elevated licking and grooming behaviors seen in the high maternal behavior animals, suggesting that OTRs mediate maternal behaviors Additional insights into the function of OT and the OTR are gained from the examination of genetically engineered mouse models.
Female OT knockout OTKO mice show normal parturition and maternal behavior but are unable to nurse their pups demonstrating that in the mouse OT is not necessary for maternal behavior or labor but is essential for milk ejection Wild-type animals investigate a novel conspecific for a longer period of time than a familiar animal, whereas OTKOs and OTRKOs show similar investigation times for both novel and familiar animals 15 Interestingly, OTKO offspring generated from a homozygous breeding scheme demonstrated an increased aggression phenotype as compared to those bred from heterozygous parents, suggesting that OT from the heterozygous dam can prevent the aggressive phenotype in the OTKO pups Although these changes in behavior may relate to the absence of OT or the OTR, these phenotypic changes could be due to compensatory mechanisms that occur during development to overcome the absence of OT signaling.
Oxytocin Powerless Without Estrogen? Maybe no help here then | Reuniting
Furthermore, selective knockout of OTRs in the LS showed that OT plays a bi-directional role in fear regulation dependent on social context. Animals exposed to a non-fearful conspecific [positive social encounter; 19 ] or to social defeat [negative social encounter; 20 ] during contextual fear conditioning showed reduced or increased fear, respectively, compared to controls.
Intra-LS administration of OTA or of a virally linked Cre-recombinase to knockdown OTR expression prevented the altered fear response mediated by the social stimulus 19 Various factors influence OT signaling.
OTRs are largely expressed centrally but their regional localization varies across species. These species-specific differences in localization may account for different responses to OT, for example, mice and rats respond differently to OT administration Additionally, mice and humans show different OTR localization.
OTR signaling also changes during development in rats with transient developmental patterns displayed postnatally, an adult-like expression pattern seen around postnatal day 21, and increased OTR quantities into adulthood Additionally, OT signaling differs between males and females. These differences between males and females may relate to hormone differences, which alter OT signaling and are discussed in more detail in a later section.
The release of CRF into the hypophyseal portal system enhances synthesis and release of adrenocorticotropic hormone ACTH from the anterior pituitary.Pregnancy hormones - Hormones during pregnancy
Increased levels of circulating glucocorticoids can further inhibit HPA axis activity via glucocorticoid and mineralocorticoid receptors in the brain as well as acting upon specific brain sites to modulate behaviors Oxytocin can putatively impact several sites within the HPA axis.
PVN neurons that project to the median eminence release OT into the hypophyseal portal vasculature to stimulate adrenal glucocorticoid release by potentiating the actions of CRF at the anterior pituitary level in a similar fashion to the closely related neuropeptide vasopressin By contrast, OT neurons in the PVN that project into the forebrain and release OT in response to stressors 29 exert anxiolytic actions 5. Interestingly, OT also promotes social buffering in response to stress, similar to the effect seen with fear MRFs are expressed in a time-dependent manner and regulate differentiation of muscular cells, in particular they control the fusion of myoblasts MBs mononucleated muscle precursor into multinucleated cells called myotubes MTs Dedieu et al.
Growth-promoting agents are purported to increase skeletal muscle fiber size and they could be illegally used to improve sport performances or meat production. In particular, De Jager et al.
Moreover, Oxt precursor gene is increased in bovine skeletal muscle in the late stages of foetal development De Jager et al. In mammals OXT is mainly synthesized in the central nervous system and it induces uterine contractions during parturition and milk ejection during lactation.
Many studies demonstrated that OXT has various metabolic effects in particular on muscular metabolism and regeneration, glucose metabolism, lipid profile and insulin sensitivity.
In skeletal muscle OXT exerts its activity promoting glucose uptake and inducing lypolisis Elabd et al. Similarly, E2 is intensively studied for its influence on energy balance, skeletal muscle and adipose tissue metabolism and glucose uptake regulation, but its role is still partially unclear Ropero et al. In particular, it was verified if E2 and OXT could influence myofibers metabolism gene regulation.
For this purpose, the C2C12 cell line was treated with E2, OXT or a combination of both molecules to assess the regulation of myogenic regulatory factors genes MRFsmyosin heavy chain Myh and some factors involved in adipogenesis, such Fabp3, Fabp4 and Pparg. Phenol red-free medium was used throughout the experiments to avoid its weak estrogen-like activity.
Subsequently, trials of acute and chronic administration of E2 were conducted on MTs to study gene expression modifications. For the acute treatment trial, MTs were grown to day 6 and then starved with media containing stripped horse serum for 24 h before the E2 treatment Sigma.