Direct Involvement of Androgen Receptor in Oxytocin Gene Expression: Possible Relevance for Mood Disorders

Dai, Dongfang; Li, Qiaochu; Zhu, Qiong-Bin; Hu, Shaohua; Balesar, Rawien; Swaab, Dick F.; Bao, Ai-Min

doi:10.1038/npp.2017.76

Cited by 35 publications

(24 citation statements)

References 48 publications

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“…AR is also co-expressed within oxytocin neurons in the medial parvocellular division of the PVN (mpvPVN) but not in magnocellular oxytocin neurons in rats [235]. In humans, oxytocin/AR co-labeled neurons are also found in the PVN [257] and T treatment of a human neuroblastoma cell line reduces oxytocin mRNA through an AR-mediated mechanism [257]. Together these studies indicate the potential for androgens and their metabolites to regulate expression and function of PVN oxytocin neurons.…”

Section: Oxytocinmentioning

confidence: 99%

Roles for androgens in mediating the sex differences of neuroendocrine and behavioral stress responses

et al. 2020

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Estradiol and testosterone are powerful steroid hormones that impact brain function in numerous ways. During development, these hormones can act to program the adult brain in a male or female direction. During adulthood, gonadal steroid hormones can activate or inhibit brain regions to modulate adult functions. Sex differences in behavioral and neuroendocrine (i.e., hypothalamic pituitary adrenal (HPA) axis) responses to stress arise as a result of these organizational and activational actions. The sex differences that are present in the HPA and behavioral responses to stress are particularly important considering their role in maintaining homeostasis. Furthermore, dysregulation of these systems can underlie the sex biases in risk for complex, stress-related diseases that are found in humans. Although many studies have explored the role of estrogen and estrogen receptors in mediating sex differences in stress-related behaviors and HPA function, much less consideration has been given to the role of androgens. While circulating androgens can act by binding and activating androgen receptors, they can also act by metabolism to estrogenic molecules to impact estrogen signaling in the brain and periphery. This review focuses on androgens as an important hormone for modulating the HPA axis and behaviors throughout life and for setting up sex differences in key stress regulatory systems that could impact risk for disease in adulthood. In particular, impacts of androgens on neuropeptide systems known to play key roles in HPA and behavioral responses to stress (corticotropin-releasing factor, vasopressin, and oxytocin) are discussed. A greater knowledge of androgen action in the brain is key to understanding the neurobiology of stress in both sexes.

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Section: Oxytocinmentioning

confidence: 99%

Roles for androgens in mediating the sex differences of neuroendocrine and behavioral stress responses

et al. 2020

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“…These considerations rendered it crucial to do postmortem brain research on the OXT system in the brain in clinically and neuropathologically well-characterized patients with mood disorders. Activation of OXT neurons has indeed been found in depression and may be related to decreased appetite and weight loss in this disease, due to the central effects of this neuropeptide as a satiety hormone (Gimpl and Fahrenholz, 2001; Meynen et al, 2007; Purba et al, 1996; Dai et al, 2017). Enhanced OXT production in the PVN was indeed found in postmortem material of melancholic depressed patients (Meynen et al, 2007).…”

Section: Introductionmentioning

confidence: 97%

The human hypothalamus in mood disorders: The HPA axis in the center

2019

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There are no specific structural neuropathological hallmarks found in the brain of mood disorders. Instead, there are molecular, functional and structural alterations reported in many brain areas. The neurodevelopmental underpinning indicated the presence of various genetic and developmental risk factors. The effect of genetic polymorphisms and developmental sequalae, some of which may start in the womb, result in functional changes in a network mediated by neurotransmitters and neuropeptides, which make the emotion- and stress-related brain systems more vulnerable to stressful events. This network of stress-related neurocircuits consists of, for instance, brainstem nuclei, the amygdala, habenula, prefrontal cortex and hypothalamus. Various nuclei of the hypothalamus form indeed one of the crucial hubs in this network. This structure concerns not only the hypothalamo-pituitary-adrenal (HPA) axis that integrate the neuro-endocrine-immune responses to stress, but also other hypothalamic nuclei and systems that play a key role in the symptoms of depression, such as disordered day-night rhythm, lack of reward feelings, disturbed eating, sex, and disturbed cognitive functions. The present review will focus on the changes in the human hypothalamus in depression, with the HPA axis in the center. We will discuss the inordinate network of neurotransmitters and neuropeptides involved, with the hope to find the most vulnerable neurobiological systems and the possible development of tailor-made treatments for mood disorders in the future.

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“…However, it is clearly known that testosterone and oxytocin have opposite effects in neuropsychiatric disorders, cognitive and behavioral functions that might be based upon a direct inhibition of AR on oxytocin transcription [ 35 ]. A recent study has proposed a clear opposing effect of testosterone and oxytocin in the modulation of psychiatric disorders such as bipolar disorder and major depressive disorder in diabetic patients [ 36 , 37 ]. Short ( CAG )n repeats would have been expected to increase the effects of testosterone and to decrease oxytocin.…”

Section: Discussionmentioning

confidence: 99%

Longer trinucleotide repeats of androgen receptor are associated with higher testosterone and low oxytocin levels in diabetic premature ejaculatory dysfunction patients

Khan¹,

Bhatti

Abbas³

et al. 2018

Basic Clin. Androl.

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BackgroundDespite its worldwide high occurrence, the obscurity regarding the description, epidemiology and management of premature ejaculation remains provocative. It is well established that male premature ejaculatory dysfunction is an increasing problem due to spontaneous ejaculation across a variety of general and clinical subjects. The main goal of this study was to determine the relationships between trinucleotide repeats of the androgen receptor (AR), sex steroids, and pituitary hormones with sexual function in men with type 2 diabetes mellitus (DM) and reported with acquired premature ejaculation (PE).MethodsA total of 150 normal and 250 PE + DM subjects were enrolled in this study. Each subject was invited to fill out an elaborative questionnaire to acquire precise selective information regarding BMI, duration of PE + DM, self-reported Intra-Vaginal Ejaculatory Latency Time (IELT), sexual and mental health status by using the premature ejaculation diagnostic tool (PEDT) and Beck Depression Inventory-II (BDI-II). Pearson’s correlation analysis was used to analyze the relationship between clinical, hormonal, and genetic variables. Ward’s minimum variance cluster analysis and principal component analysis were used for evaluation of dependence between genetic, clinical, and demographic parameters.ResultsThe patients who have the lowest number of (≤21) (CAG)n repeats have higher serum oxytocin levels (114.2 pg/ml; n = 54, 43.2%) than the controls (69.18 pg/ml; n = 22, 17.6%) and the patients with the highest (≥26) number of (CAG)n repeats (62.9 pg/ml; n = 108, 43.2%).On the other hand, patients who have the highest numbers of (CAG)n repeats (≥26) have higher serum testosterone (6.1 ng/ml; n = 108, 43.2% of cohort) lower prolactin (3.01 ng/ml; n = 108, 43.2% of cohort) levels than the controls and patients with the lowest numbers (≤21) of (CAG)n repeats and their TSH (1.53 mIU/L, P < 0.05) levels are lower than those of controls. In the Pearson correlation model, self-estimated IELT demonstrated significantly negative correlation with both (CAG)n and (GCC)n repeats (r = − 0.16, p = 0.0001; r = − 0.19, p = 0.0001) respectively. These repeats have positive correlation with PEDT (r = 0.28, p = 0.0001: r = 0.24, p = 0.0001, whole model) and inversely correlated with BDI-II (r = − 0.25, p = 0.0001).ConclusionThis study indicates that androgen receptor polymorphism modulates the endocrine effect on ejaculatory reflex and depends strongly on its “cofactors”. Moreover, our results also confirmed an association between long tri-nucleotide repeats of androgen receptor, sex steroids, pituitary, and thyroid hormones in relation to acquired premature ejaculatory dysfunction in diabetic patients. However, endocrine regulation of PE reflex is a complex phenomenon that requires further investigation.

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Direct Involvement of Androgen Receptor in Oxytocin Gene Expression: Possible Relevance for Mood Disorders

Cited by 35 publications

References 48 publications

Roles for androgens in mediating the sex differences of neuroendocrine and behavioral stress responses

Roles for androgens in mediating the sex differences of neuroendocrine and behavioral stress responses

The human hypothalamus in mood disorders: The HPA axis in the center

Longer trinucleotide repeats of androgen receptor are associated with higher testosterone and low oxytocin levels in diabetic premature ejaculatory dysfunction patients

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