Glucocorticoid receptor exhibits sexually dimorphic expression in the medaka brain

Kikuchi, Yukiko; Hosono, Kohei; Yamashita, Jirô; Kawabata, Yukika; Okubo, Kataaki

doi:10.1016/j.ygcen.2015.09.031

Cited by 15 publications

(7 citation statements)

References 42 publications

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“…Sex steroid hormones, including E2 and androgens, have been shown to regulate GC receptors in the brain (Ahima and Harlan, 1992, Burgess and Handa, 1993, Kerr et al, 1996, Blanco et al, 2002, Sheng et al, 2003). Sex differences in the GC receptors and GC receptor function in the brain have also been reported (McCormick et al, 1995, Goel and Bale, 2010, Zavala et al, 2011, Bourke et al, 2012, Kikuchi et al, 2015). Thus, the differential levels of sex hormones in males vs females during development may organize the brain GC system in a sex-specific manner.…”

Section: Discussionmentioning

confidence: 96%

Sex-dependent programming effects of prenatal glucocorticoid treatment on the developing serotonin system and stress-related behaviors in adulthood

et al. 2016

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Prenatal stress and overexposure to glucocorticoids (GC) during development may be associated with an increased susceptibility to a number of diseases in adulthood including neuropsychiatric disorders, such as depression and anxiety. In animal models, prenatal overexposure to GC results in hyper-responsiveness to stress in adulthood, and females appear to be more susceptible than males. Here, we tested the hypothesis that overexposure to GC during fetal development has sex-specific programming effects on the brain, resulting in altered behaviors in adulthood. We examined the effects of dexamethasone (DEX; a synthetic GC) during prenatal life on stress-related behaviors in adulthood and on the tryptophan hydroxylase-2 (TpH2) gene expression in the adult dorsal raphe nucleus (DRN). TpH2 is the rate-limiting enzyme for serotonin (5-HT) synthesis and has been implicated in the etiology of human affective disorders. Timed-pregnant rats were treated with DEX from gestational days 18–22. Male and female offspring were sacrificed on the day of birth (postnatal day 0; P0), P7, and in adulthood (P80-84) and brains were examined for changes in TpH2 mRNA expression. Adult animals were also tested for anxiety- and depressive- like behaviors. In adulthood, prenatal DEX increased anxiety- and depressive- like behaviors selectively in females, as measured by decreased time spent in the center of the open field and increased time spent immobile in the forced swim test, respectively. Prenatal DEX increased TpH2 mRNA selectively in the female caudal DRN at P7, whereas it decreased TpH2 mRNA selectively in the female caudal DRN in adulthood. In animals challenged with restraint stress in adulthood, TpH2 mRNA was significantly lower in rostral DRN of prenatal DEX treated females compared to vehicle treated females. These data demonstrated that prenatal overexposure to GC alters the development of TpH2 gene expression and these alterations correlated with lasting behavioral changes found in adult female offspring.

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Section: Discussionmentioning

confidence: 96%

Sex-dependent programming effects of prenatal glucocorticoid treatment on the developing serotonin system and stress-related behaviors in adulthood

et al. 2016

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“…This diversity may be linked to the differences in the sex steroid regulation of Oxt/it expression. It is of interest to note that another ionoregulation‐related hormone in teleosts, cortisol, has been shown to stimulate it expression in the seabream ( Sparus aurata ) brain and that circulating cortisol levels are higher in female medaka than in male medaka . Androgen may serve to compensate for the female‐biased it expression caused by cortisol in teleosts.…”

Section: Discussionmentioning

confidence: 99%

Expression of isotocin is male‐specifically up‐regulated by gonadal androgen in the medaka brain

Yamashita

Kawabata

Okubo

2017

J Neuroendocrinology

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Oxytocin, a mammalian neuropeptide primarily synthesised in the supraoptic and paraventricular nuclei of the hypothalamus, mediates a variety of physiological and behavioural processes, ranging from parturition and lactation to affiliation and prosociality. Multiple studies in rodents have shown that the expression of the oxytocin gene (Oxt) is stimulated by oestrogen, whereas androgen has no apparent effect. However, this finding is not consistent across all studies, and no study has examined sex steroid regulation of Oxt or its orthologues in other animals. In the present study, we show that, in the teleost fish, medaka (Oryzias latipes), the expression of the isotocin gene (it), the teleost orthologue of Oxt, in the parvocellular preoptic nuclei (homologous to the mammalian supraoptic nucleus) is male-specifically up-regulated by gonadal androgen, whereas it expression in the magnocellular/gigantocellular preoptic nuclei (homologous to the mammalian paraventricular nucleus) is independent of sex steroids in both sexes. None of the it-expressing neurones appear to co-express androgen receptors, suggesting that the effect of androgen on it expression is indirect. We found that the expression of a kisspeptin gene, kiss2, in the male brain is dependent on gonadal androgen, raising the possibility that the androgen-dependent expression of it may be mediated by kiss2 neurones. Our data also show that the isotocin peptide synthesised in response to androgen is axonally transported to the posterior pituitary to act peripherally. Given that levels of it expression are higher in females than in males, androgen may serve to compensate for the female-biased it expression to ensure a role for isotocin that is equally important for both sexes. These results are unexpectedly quite different from those reported in rodents, indicating that the regulatory role of sex steroids in Oxt/it expression has diverged during evolution, possibly with accompanying changes in the role of oxytocin/isotocin.

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“…GR exhibits female-biased expression in several preoptic and thalamic nuclei, thus indicating that glucocorticoids have a greater influence on physiology and behavior, mediated by specific neuropeptides more so in females than in males ( 69 ). Since the brain plays an important role in governing the stress response, this may contribute to gender differences in CV response to stress.…”

Section: Stress Hormone Signaling and Physiological Effectsmentioning

confidence: 99%

Predisposition of Women to Cardiovascular Diseases: A Side-Effect of Increased Glucocorticoid Signaling During the COVID-19 Pandemic?

Dhaibar

Cruz‐Topete

2021

Front. Glob. Womens Health

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The novel coronavirus disease 2019 (COVID-19) pandemic has created a significant health crisis worldwide. To mitigate this disease's spread, “social distancing” and “shelter in place” have been implemented. While these actions have been critical to controlling the pandemic, they have short- and long-term mental health consequences due to increased stress. There is a strong association between mental stress and cardiovascular disease (CVD). Young women (pre-menopausal) are at high risk of developing CV events in response to mental stress compared to age-matched men. The mechanisms underlying women's increased reactivity and response to stress are mostly unknown. The present review summarizes the known physiological consequences of mental stress in women's CV health and the latest molecular findings of the actions of the primary stress hormones, glucocorticoids, on the CV system. The current data suggest a clear link between psychological stress and heart disease, and women have an increased sensitivity to the harmful effects of stress hormone signaling imbalances. Therefore, it is expected that with the given unprecedented levels of stress associated with the COVID-19 pandemic, women's CV health will be significantly compromised. It is critical to widen our understanding of the direct contribution of mental stress to CVD risk in women and to identify biochemical markers with predictive value for CVD in female patients with/without cardiovascular conditions who have experienced significant mental stress during the current pandemic.

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Glucocorticoid receptor exhibits sexually dimorphic expression in the medaka brain

Cited by 15 publications

References 42 publications

Sex-dependent programming effects of prenatal glucocorticoid treatment on the developing serotonin system and stress-related behaviors in adulthood

Sex-dependent programming effects of prenatal glucocorticoid treatment on the developing serotonin system and stress-related behaviors in adulthood

Expression of isotocin is male‐specifically up‐regulated by gonadal androgen in the medaka brain

Predisposition of Women to Cardiovascular Diseases: A Side-Effect of Increased Glucocorticoid Signaling During the COVID-19 Pandemic?

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