Allopregnanolone and puberty: Modulatory effect on glutamate and GABA release and expression of 3α-hydroxysteroid oxidoreductase in the hypothalamus of female rats

Giuliani, Fernando; Escudero, Consuelo; Casas, Sebastián; Bazzocchini, Vanesa; Yunes, Roberto; Laconi, Myriam Raquel; Cabrera, Rodrigo

doi:10.1016/j.neuroscience.2013.03.053

Cited by 17 publications

(20 citation statements)

References 81 publications

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“…In several cases the physiological actions of PROG are mediated by its reduced metabolite 3a-THP (Giachino et al, 2003;Guerra-Araiza et al, 2007) and may involve the regulation of the activity of GABA-A receptors (Follesa et al, 2001;Lambert et al, 2003;Majewska et al, 1986;Wang, 2011). Indeed, 3a-THP is an important allosteric modulator of GABA-A receptor at different life stages (Biggio et al, 2009;Turkmen et al, 2011) and also regulates GABA and glutamate release (Giuliani et al, 2013). The actions of 3a-THP on the activity of GABA-A receptor may contribute to changes in mood and affection (Biggio et al, 2009;Eser et al, 2008;Turkmen et al, 2011;Wirth, 2011).…”

Section: Physiological Actions Of Progesterone and Its Metabolites Inmentioning

confidence: 99%

Levels and actions of progesterone and its metabolites in the nervous system during physiological and pathological conditions

Melcangi

Giatti

Calabrese

et al. 2014

Progress in Neurobiology

116

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Progesterone is synthesized and actively metabolized in the central and peripheral nervous system, into neuroactive steroid metabolites, such as dihydroprogesterone, allopregnanolone and isopregnanolone. Progesterone and/or its metabolites exert a variety of effects acting as physiological regulators of neuronal and glial development and plasticity, controlling reproduction, neuroendocrine events, mood and affection. In addition, these neuroactive steroids maintain neural homeostasis and exert neuroprotective actions. In agreement, metabolic pathways of progesterone are affected by modifications in the level of gonadal hormones and by pathology or injury with a regional specificity and in a sex-dimorphic way. Therefore, observations here summarized may provide a background to design sex-specific therapies based on progesterone metabolites. On this point of view, considering that one of the major limits of a therapy based on neuroactive steroids could be modifications in their plasma levels and their consequent peripheral effects, pharmacological treatments aimed to increase their levels in the nervous system could provide an interesting therapeutic option.

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Section: Physiological Actions Of Progesterone and Its Metabolites Inmentioning

confidence: 99%

Levels and actions of progesterone and its metabolites in the nervous system during physiological and pathological conditions

Melcangi

Giatti

Calabrese

et al. 2014

Progress in Neurobiology

116

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“…with hypothalamic neurons, in particular, NPY/AgRP [23] and KNDy [24]. Activity of neurotransmitters [25-28] and expression of growth factors (IGF-1) [29] in the hypothalamus are associated with the onset of puberty and the reproductive cycle in females. However, little is known about the effects of perinatal exposure to EDCs on expression of the genes associated with these signals in the hypothalamus and especially in the ARC.…”

Section: Introductionmentioning

confidence: 99%

Regulation of arcuate genes by developmental exposures to endocrine-disrupting compounds in female rats

Roepke

Yang

Yasrebi

et al. 2016

Reproductive Toxicology

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Developmental exposure to endocrine-disrupting compounds (EDCs) alters reproduction and energy homeostasis, both of which are regulated by the arcuate nucleus (ARC). Little is known about the effects of EDC on ARC gene expression. In Experiment #1, pregnant dams were treated with either two doses of bisphenol A (BPA) or oil from embryonic day (E)18-21. Neonates were injected from postnatal day (PND)0-7. Vaginal opening, body weights, and ARC gene expression were measured. Chrm3 (muscarinic receptor 3) and Adipor1 (adiponectin receptor 1) were decreased by BPA. Bdnf (brain-derived neurotropic factor), Igf1 (insulin-like growth factor 1), Htr2c (5-hydroxytryptamine receptor), and Cck2r (cholescystokinin 2 receptor) were impacted. In Experiment #2, females were exposed to BPA, diethylstilbestrol (DES), di(2-ethylhexyl)phthalate, or methoxychlor (MXC) during E11-PND7. MXC and DES advanced the age of vaginal opening and ARC gene expression was impacted. These data indicate that EDCs alter ARC genes involved in reproduction and energy homeostasis in females.

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“…The dose of ALLO used in the experiments (6 μmol L ‐1 = 6000 Nm) was obtained by dilutions in Krebs Ringer bicarbonate glucose buffer (KRBG) at pH 7.4, to make the final amount of propylene glycol negligible. Bicuculline methiodide (4.9 µmol L ‐1 = 4900 nmol L ‐1 ), dextrose, ascorbic acid and bovine serum albumin fraction V (BSA) were provided by Sigma Chemical Co. 1,2,6,7‐[ 3 H]‐Progesterone (107.0 Ci mmol ‐1 ) was provided by New England Nuclear Products (Boston, MA, USA). Bouin solution (Biopur Diagnostics, Santa Fe, Argentina) and Canada Balsam Synthetic (Biopack, Buenos Aires, Argentina) were purchased for histological procedures.…”

Section: Methodsmentioning

confidence: 99%

“…In the hypothalamus, ALLO influences the excitability of GABAergic neurones by interacting with the GABA A receptor . In this way, it inhibits the release of gonadotrophin‐releasing hormone (GnRH) . Furthermore, the hypothalamic steroidogenesis is an important factor that regulates the luteinising hormone (LH) surge in pro‐oestrus and, therefore, regulates the oestrous cycle .…”

Section: Introductionmentioning

confidence: 99%

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“Rapid actions of the neurosteroid allopregnanolone on ovarian and hypothalamic steroidogenesis: Central and peripheral modulation”

Cáceres

Orozco

Cabrera

et al. 2020

J Neuroendocrinology

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The present study aimed to determine whether an i.c.v. administration of allopregnanolone (ALLO) rapidly modifies the hypothalamic and ovarian 3β‐hydroxysteroid dehydrogenase (3β‐HSD) enzymatic activity and gene expression in in vivo and ex vivo systems in pro‐oestrus (PE) and dioestrus I (DI) rats. Animals were injected with vehicle, ALLO, bicuculline or bicuculline plus ALLO and were then killed. In the in vivo experiment, the hypothalamus, ovaries and serum were extracted and analysed. In the ex vivo experiment, the superior mesenteric ganglion ‐ ovarian nerve plexus ‐ ovary system was extracted and incubated during 120 minutes at 37 ºC. The serum and ovarian compartment fluids were used to determine progesterone by radioimmunoanalysis. In the in vivo experiments, ALLO caused a decrease in hypothalamic and ovarian 3β‐HSD enzymatic activity during PE. During DI, ALLO increased hypothalamic and ovarian 3β‐HSD activity and gene expression. The ovarian 3β‐HSD activity increased in both stages in the ex vivo system; gene expression increased only during DI. ALLO induced an increase in serum progesterone only in D1 and in the ovarian incubation liquids in both stages. All findings were reversed by an injection of bicuculline before ALLO. Ovarian steroidogenic changes could be attributed to signals coming from ganglion neurones, which are affected by the acute central neurosteroid stimulation. The i.c.v. administration of ALLO via the GABAergic system altered 3β‐HSD activity and gene expression, modulating the neuroendocrine axis. The present study reveals the action that ALLO exerts on the GABAA receptor in both the central and peripheral nervous system and its relationship with hormonal variations. ALLO is involved in the “fine tuning” of neurosecretory functions as a potent modulator of reproductive processes in female rats.

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Allopregnanolone and puberty: Modulatory effect on glutamate and GABA release and expression of 3α-hydroxysteroid oxidoreductase in the hypothalamus of female rats

Cited by 17 publications

References 81 publications

Levels and actions of progesterone and its metabolites in the nervous system during physiological and pathological conditions

Levels and actions of progesterone and its metabolites in the nervous system during physiological and pathological conditions

Regulation of arcuate genes by developmental exposures to endocrine-disrupting compounds in female rats

“Rapid actions of the neurosteroid allopregnanolone on ovarian and hypothalamic steroidogenesis: Central and peripheral modulation”

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