Action by and sensitivity to neuroactive steroids in menstrual cycle related CNS disorders

N-Wihlbäck, Anna-Carin; Sundström‐Poromaa, Inger; Bäckström, Torbjörn

doi:10.1007/s00213-005-0185-2

Cited by 43 publications

(27 citation statements)

References 163 publications

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“…[47][48][49] Low doses of allopregnanolone increase aggressive behavior in mice, whereas higher doses decrease aggression. 50 Moreover, the addition of a low dose of progesterone to the treatment with estradiol during hormonal replacement therapy increases negative mood, but higher doses do not.…”

Section: Discussionmentioning

confidence: 99%

Progesterone selectively increases amygdala reactivity in women

et al. 2007

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The acute neural effects of progesterone are mediated by its neuroactive metabolites allopregnanolone and pregnanolone. These neurosteroids potentiate the inhibitory actions of c-aminobutyric acid (GABA). Progesterone is known to produce anxiolytic effects in animals, but recent animal studies suggest that pregnanolone increases anxiety after a period of low allopregnanolone concentration. This effect is potentially mediated by the amygdala and related to the negative mood symptoms in humans that are observed during increased allopregnanolone levels. Therefore, we investigated with functional magnetic resonance imaging (MRI) whether a single progesterone administration to healthy young women in their follicular phase modulates the amygdala response to salient, biologically relevant stimuli. The progesterone administration increased the plasma concentrations of progesterone and allopregnanolone to levels that are reached during the luteal phase and early pregnancy. The imaging results show that progesterone selectively increased amygdala reactivity. Furthermore, functional connectivity analyses indicate that progesterone modulated functional coupling of the amygdala with distant brain regions. These results reveal a neural mechanism by which progesterone may mediate adverse effects on anxiety and mood.

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Section: Discussionmentioning

confidence: 99%

Progesterone selectively increases amygdala reactivity in women

et al. 2007

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“…Clinical investigations have been performed to understand the effect of P 4 on moods associated with premenstrual dysphoric disorder (PMDD) [154]. PMDD is defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV, APA 1994) as a cluster of both negative mood symptoms and physical symptoms that occur during the luteal phase of the menstrual cycle (when P 4 and APα levels are high) and disappear several days following the onset of menstruation (when P 4 and APα levels are low).…”

Section: Progesterone Regulation Of Memory and Neuronal Excitabilitymentioning

confidence: 99%

Progesterone receptors: Form and function in brain

Brinton

Thompson

Foy

et al. 2008

Frontiers in Neuroendocrinology

584

443

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Emerging data indicate that progesterone has multiple non-reproductive functions in the central nervous system to regulate cognition, mood, inflammation, mitochondrial function, neurogenesis and regeneration, myelination and recovery from traumatic brain injury. Progesterone-regulated neural responses are mediated by an array of progesterone receptors (PR) that include the classic nuclear PRA and PRB receptors and splice variants of each, the seven transmembrane domain 7TMPRβ and the membrane-associated 25-Dx PR (PGRMC1). These PRs induce classic regulation of gene expression while also transducing signaling cascades that originate at the cell membrane and ultimately activate transcription factors. Remarkably, PRs are broadly expressed throughout the brain and can be detected in every neural cell type. The distribution of PRs beyond hypothalamic borders, suggests a much broader role of progesterone in regulating neural function. Despite the large body of evidence regarding progesterone regulation of reproductive behaviors and estrogen-inducible responses as well as effects of progesterone metabolite neurosteroids, much remains to be discovered regarding the functional outcomes resulting from activation of the complex array of PRs in brain by gonadally and / or glial derived progesterone. Moreover, the impact of clinically used progestogens and developing selective PR modulators for targeted outcomes in brain is a critical avenue of investigation as the non-reproductive functions of PRs have far-reaching implications for hormone therapy to maintain neurological health and function throughout menopausal aging.

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“…It is generally held that disruptions in the normal interplay between neuroactive steroids and their brain targets underlie the pathogenesis of negative affective states associated with periods of hormonal fluctuation such as the premenstruum, puerperium and perimenopause (Epperson et al, 1999;Bernardi et al, 2004;Eriksson et al, 2006;N-Wihlback et al, 2006;Sundstrom-Poromaa et al, 2003). Although the majority of women experience some mood and/or physical symptoms before or during their period, between 3 and 8% of premenopausal women experience the more severe mood disorder known as premenstrual dysphoric disorder (PMDD).…”

Section: Introductionmentioning

confidence: 99%

Luteal-Phase Accentuation of Acoustic Startle Response in Women with Premenstrual Dysphoric Disorder

Epperson

Pittman

Czarkowski

et al. 2007

Neuropsychopharmacol

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Alterations in central nervous system response to menstrual cycle-related fluctuations in neuroactive steroids are thought to underlie the emergence of negative affect in the luteal phase of the menstrual cycle in women with premenstrual dysphoric disorder (PMDD). Such changes in the neuroendocrine milieu may lead to heightened arousal and response to stress in women with PMDD. Using the acoustic startle paradigm, we sought to determine whether women with PMDD have an accentuated physiologic response to a mildly aversive stimulus during the luteal compared to follicular phase. Further, we also examined the impact of visual affective stimuli on acoustic startle response (ASR) magnitude. During the follicular and luteal phases of the menstrual cycle, acoustic stimuli (103 dB) were delivered to 15 women with PMDD and 14 healthy menstruating women of similar age. After obtaining baseline ASR, the procedure was repeated when subjects viewed pleasant, neutral and unpleasant pictures. There was a significant group by menstrual cycle phase interaction for baseline ASR magnitude, which can be attributed to the heightened startle magnitude in women with PMDD compared to healthy women during the luteal relative to the follicular phase. The direction and degree to which picture viewing modulated the startle magnitude did not vary by group or menstrual cycle phase. These data suggest that menstrual cycle phase has a powerful modulatory effect on physiologic reactivity in women with PMDD but not in healthy women. Physiologic response to affective stimuli appears to be intact in women with PMDD across the menstrual cycle.

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Action by and sensitivity to neuroactive steroids in menstrual cycle related CNS disorders

Cited by 43 publications

References 163 publications

Progesterone selectively increases amygdala reactivity in women

Progesterone selectively increases amygdala reactivity in women

Progesterone receptors: Form and function in brain

Luteal-Phase Accentuation of Acoustic Startle Response in Women with Premenstrual Dysphoric Disorder

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