Neurosteroids: A Novel Function of the Brain

Baulieu, E E

doi:10.1016/s0306-4530(98)00071-7

Cited by 547 publications

(325 citation statements)

References 71 publications

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“…These roles of Sig-1R might be achieved by binding of Sig-1R ligands or by an increase in the concentrations of Sig-1R-binding steroids in response to stress or the menstrual cycle (41). Finally, because Sig-1R have been implicated in actions of certain psychotropic drugs including cocaine (12-14, 19, 20, 42, 43), further understanding of the ankyrin B dynamics regulated by Sig-1R may pave a new avenue in psychopharmacology linking certain actions of psychotropic drugs to the dynamics and functions of cytoskeletal proteins.…”

Section: Discussionmentioning

confidence: 99%

Regulating ankyrin dynamics: Roles of sigma-1 receptors

Hayashi¹

2001

Proceedings of the National Academy of Sciences

162

183

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Section: Discussionmentioning

confidence: 99%

Regulating ankyrin dynamics: Roles of sigma-1 receptors

Hayashi¹

2001

Proceedings of the National Academy of Sciences

162

183

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“…Naturally occurring neurosteroids are synthesized from cholesterol in both peripheral organs and in the central nervous system (CNS), primarily by glial cells, and can be classified as positive (enhancing) or negative (blocking) allosteric modulators of the GABA A receptor (for review, Baulieu, 1998;Compagnone and Mellon, 2000;Belelli and Lambert, 2005). Synthetic steroids, including anesthetics such as alphaxalone and ganaxolone (for review, Belelli and Lambert, 2005) and the anabolic androgenic steroids (AAS) (for review, Clark et al, 2004;2006) also act as allosteric modulators of the GABA A receptor.…”

Section: Introductionmentioning

confidence: 99%

Steroid modulation of GABAA receptor-mediated transmission in the hypothalamus: Effects on reproductive function

Henderson

2007

Neuropharmacology

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The hypothalamus, the seat of neuroendocrine control, is exquisitely sensitive to gonadal steroids. For decades it has been known that androgens, estrogens and progestins, acting through nuclear hormone receptors, elicit both organizational and activational effects in the hypothalamus and basal forebrain that are essential for reproductive function. While changes in gene expression mediated by these classical hormone pathways are paramount in governing both sexual differentiation and the neural control of reproduction, it is also clear that steroids impart critical control of neuroendocrine functions through nongenomic mechanisms. Specifically, endogenous neurosteroid derivatives of deoxycorticosterone, progesterone and testosterone, as well and synthetic anabolic androgenic steroids that are self-administered as drugs of abuse, elicit acute effects via allosteric modulation of γ-aminobutyric acid type A receptors. GABAergic transmission within the hypothalamus and basal forebrain is a key regulator of pubertal onset, the expression of sexual behaviors, pregnancy and parturition. Summarized here are the known actions of steroid modulators on GABAergic transmission within the hypothalamus/basal forebrain, with a focus on the medial preoptic area and the supraoptic/paraventricular nuclei that are known to be central players in the control of reproduction.

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“…Neuroactive steroids synthesized directly in the brain are independent from peripheral sources and rapidly alter neuronal excitability by binding to their receptors (Baulieu 1998). PS is endogenously present in the brain and synthesized by glial cells, which has been shown to modulate neurotransmission in a variety of systems via both presynaptic and postsynaptic mechanisms (Bowlby 1993).…”

Section: Introductionmentioning

confidence: 99%

Pregnenolone sulfate regulates prolactin production in the rat pituitary

Kang

Hong

Lee

et al. 2016

Journal of Endocrinology

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Pregnenolone sulfate (PS) is a neuroactive steroid hormone produced in the brain. In this study, the effects of PS on synthesis and secretion of rat pituitary prolactin (PRL) were examined. To accomplish this, GH3 rat pituitary adenoma cells were treated with PS, which showed significantly increased mRNA and protein levels of PRL compared with the control. The mechanism of action responsible for the effects of PS on PRL synthesis and secretion was investigated by pretreating cells with inhibitors of traditional PRLor the PS-related signaling pathway. PS-stimulated PRL transcription was significantly reduced by inhibitors of PKA, PKC and MAPK, but unchanged by GABAAR and NMDAR inhibitors. Western blotting analysis revealed that the total ERK1/2 level was upregulated in a time-dependent manner following PS treatment. An approximate 10% increase in GH3 cell proliferation was also observed in response to PS relative to the control. In the animal study, levels of PRL in the pituitary and in serum were elevated by PS. PS-stimulated PRL synthesis was also found to be associated with decreased expression of PRL target genes such as GNRH1, FSHB and LHB. These findings show that PS upregulates PRL synthesis and secretion in vivo and in vitro via MAPK signaling, suggesting that it has the potential for use as a therapeutic hormone to treat PRLrelated disorders such as hypoprolactinemia and low milk supply.

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Neurosteroids: A Novel Function of the Brain

Cited by 547 publications

References 71 publications

Regulating ankyrin dynamics: Roles of sigma-1 receptors

Regulating ankyrin dynamics: Roles of sigma-1 receptors

Steroid modulation of GABAA receptor-mediated transmission in the hypothalamus: Effects on reproductive function

Pregnenolone sulfate regulates prolactin production in the rat pituitary

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