Central Opioid Inhibition of Neuroendocrine Stress Responses in Pregnancy in the Rat Is Induced by the Neurosteroid Allopregnanolone

Brunton, Paula; McKay, Ailsa; Ochędalski, Tomasz; Piastowska, A.W.; Rębas, Elżbieta; Lachowicz, Agnieszka; Russell, John A.

doi:10.1523/jneurosci.0708-09.2009

Cited by 112 publications

(153 citation statements)

References 57 publications

(63 reference statements)

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“…Allopregnanolone decreases the HPA response in pregnant rodents [20] and in addition to the direct GABA-enhancing effect, allopregnanolone administration affects the transcription of genes involved in HPA-axis regulation in rats [47]. Thus, there is a possibility that the association seen in our study is mediated by HPA-axis regulation effects on mood [48].…”

Section: Discussionmentioning

confidence: 97%

Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy

et al. 2014

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Background: Allopregnanolone (3α-hydroxy-5α-pregnan-20-one) is a neurosteroid which has an inhibitory function through interaction with the GABA_A receptor. This progesterone metabolite has strong sedative and anxiolytic properties, and low endogenous levels have been associated with depressed mood. This study aimed to investigate whether the very high serum allopregnanolone levels in late pregnancy covary with concurrent self-rated symptoms of depression and anxiety. Methods: Ninety-six women in pregnancy weeks 37-40 rated symptoms of depression and anxiety with the Montgomery-Åsberg Depression Rating Scale (MADRS-S) and Spielberger State-Trait Anxiety Inventory. Their serum allopregnanolone was analyzed by Celite chromatography and radioimmunoassay. Results: Ten women had elevated depression scores (MADRS-S ≥13), and this group had significantly lower allopregnanolone levels compared to women with MADRS-S scores in the normal range (39.0 ± 17.9 vs. 54.6 ± 18.7 nmol/l, p = 0.014). A significant negative correlation was found between self-rated depression scores and allopregnanolone concentrations (Pearson's correlation coefficient = -0.220, p = 0.031). The linear association between self-rated depression scores and allopregnanolone serum concentrations remained significant when adjusted for gestational length, progesterone levels, and parity. Self-rated anxiety, however, was not associated with allopregnanolone serum concentrations during pregnancy. Conclusion: High allopregnanolone serum concentrations may protect against depressed mood during pregnancy.

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Section: Discussionmentioning

confidence: 97%

Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy

et al. 2014

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“…Allopregnanolone is a potent gamma-aminobutyric acid (GABA) agonist, and during pregnancy, rising progesterone leads to elevated central allopregnanolone levels, which inhibit stress reactivity. 13 After birth, falling allopregnanolone levels necessitate rapid changes in GABA receptor expression. In a knockout mouse model, postpartum animals lacking one of the GABA subunits exhibit anxiety and poor pup caretaking behavior, but virgin animals are unaffected, suggesting that GABA function is sensitive to changing progesterone levels in the peripartum period.…”

Section: Progesteronementioning

confidence: 99%

Failed Lactation and Perinatal Depression: Common Problems with Shared Neuroendocrine Mechanisms?

Stuebe

Grewen

Pedersen

et al. 2012

Journal of Women's Health

110

105

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In the early postpartum period, mother and infant navigate a critical neuroendocrine transition from pregnancy to lactation. Two major clinical problems that occur during this transition are failed lactation and perinatal mood disorders. These disorders often overlap in clinical settings. Failed lactation is common. Although all major medical organizations recommend 6 months of exclusive breastfeeding, only 13% of women in the United States achieve this recommendation. Perinatal mood disorders affect 10% of mothers, with substantial morbidity for mother and child. We hypothesize that shared neuroendocrine mechanisms contribute to both failed lactation and perinatal mood disorders. In this hypothesis article, we discuss data from both animal models and clinical studies that suggest neuroendocrine mechanisms that may underlie these two disorders. Research to elucidate the role of these underlying mechanisms may identify treatment strategies both to relieve perinatal depression and to enable women to achieve their infant feeding goals.

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“…In the brain, 5a-reductase generates neurosteroids such as allopregnanolone (3a-hydroxy-5a-pregnan-20-one) and androstanediol (5a-androstane-3b,17b-diol), which have anxiolytic and stress-reducing actions (Bitran et al 1995, Patchev et al 1996, Edinger & Frye 2004, Brunton et al 2009, Handa et al 2009). Hence, reduced central 5a-reductase expression is consistent with the anxious and stress hyper-reactive phenotype of PNS rats (Brunton & Russell 2010).…”

Section: Figurementioning

confidence: 99%

Sex-specific effects of prenatal stress on glucose homoeostasis and peripheral metabolism in rats

Brunton¹,

Sullivan²,

Kerrigan³

et al. 2013

Journal of Endocrinology

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Glucocorticoid overexposure during pregnancy programmes offspring physiology and predisposes to later disease. However, any impact of ethologically relevant maternal stress is less clear, yet of physiological importance. Here, we investigated in rats the short-and longterm effects in adult offspring of repeated social stress (exposure to an aggressive lactating female) during late pregnancy on glucose regulation following stress, glucose-insulin homoeostasis and peripheral expression of genes important in regulating glucose and lipid metabolism and glucocorticoid action. Prenatal stress (PNS) was associated with reduced birth weight in female, but not male, offspring. The increase in blood glucose with restraint was exaggerated in adult PNS males compared with controls, but not in females. Oral glucose tolerance testing showed no effects on plasma glucose or insulin concentrations in either sex at 3 months; however, at 6 months, PNS females were hyperinsulinaemic following an oral glucose load. In PNS males, plasma triglyceride concentrations were increased, with reduced hepatic mRNA expression of 5a-reductase and peroxisome proliferator-activated receptor a (Ppara (Ppara)) and a strong trend towards reduced peroxisome proliferatoractivated receptor gamma coactivator 1a (Pgc1a (Ppargc1a)) and Pparg (Pparg) expression, whereas only Pgc1a mRNA was affected in PNS females. Conversely, in subcutaneous fat, PNS reduced mRNA expression of 11b-hydroxysteroid dehydrogenase type 1 (11bhsd1), phosphoenolpyruvate carboxykinase (Pepck (Pck1)), adipose triglyceride lipase (Atgl) and diglyceride acyltransferase 2 (Dgat2) in females, but only Pepck mRNA expression was reduced in PNS males. Thus, prenatal social stress differentially programmes glucose homoeostasis and peripheral metabolism in male and female offspring. These long-term alterations in physiology may increase susceptibility to metabolic disease.Key Words " 5a-reductase " adipose " corticosterone metabolism " early life stress " liver " sex difference

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Central Opioid Inhibition of Neuroendocrine Stress Responses in Pregnancy in the Rat Is Induced by the Neurosteroid Allopregnanolone

Cited by 112 publications

References 57 publications

Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy

Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy

Failed Lactation and Perinatal Depression: Common Problems with Shared Neuroendocrine Mechanisms?

Sex-specific effects of prenatal stress on glucose homoeostasis and peripheral metabolism in rats

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