Neurosteroid modulation of allopregnanolone and GABA effect on the GABA-A receptor

Strömberg, Jessica; Haage, David; Taube, Magdalena; Bäckström, Torbjörn; Lundgren, Per

doi:10.1016/j.neuroscience.2006.07.031

Cited by 41 publications

(40 citation statements)

References 45 publications

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“…The reason for this relationship is probably that a metabolism of isoallopregnanolone into allopregnanolone could occur, a phenomenon observed earlier [34]. The lack of effect on gonadotropins in the ISOALLO group supports the theory that the allopregnanolone decreasing effect on gonadotropin secretion is mediated through a specific GABA A receptor activation and not an unspecific steroidal effect [35].…”

Section: Discussionsupporting

confidence: 63%

Allopregnanolone, a GABA_Areceptor agonist, decreases gonadotropin levels in women. A preliminary study

Timby

Hedström

Bäckström

et al. 2010

Gynecological Endocrinology

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Allopregnanolone, a GABA-A receptor agonist, decreases gonadotropin levels in women. A preliminary study. Isoallopregnanolone is an isomer to allopregnanolone, but without GABA A receptor effects.The purpose of this study was to investigate effects of allopregnanolone and isoallopregnanolone on gonadotropin levels in healthy women of fertile age. Ten women were given allopregnanolone and five women isoallopregnanolone intravenously in follicular phase. Repeated blood samples were drawn during the test day. Main outcomes were changes in serum levels of FSH, LH, oestradiol and progesterone.Serum-FSH decreased between 5 and 105 minutes after the allopregnanolone injection

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Section: Discussionsupporting

confidence: 63%

Allopregnanolone, a GABA_Areceptor agonist, decreases gonadotropin levels in women. A preliminary study

Timby

Hedström

Bäckström

et al. 2010

Gynecological Endocrinology

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“…Due to high concentration of isoallopregnanolone the metabolism is most probably in the direction from isoallopregnanolone to allopregnanolone and a higher allopregnanolone concentration can be assumed in the brain than in plasma. However, we can not exclude the possibility that isoallopregnanolone has an effect of its own, even though earlier in vivo and in vitro studies have not been able to show it (Gyermek 1968;Lundgren et al 2003;Stromberg et al 2006).…”

Section: Discussionmentioning

confidence: 70%

“…The antagonizing effect of isoallopregnanolone on allopregnanolone seems specific as GABA, benzodiazepine or barbiturate effects are not inhibited by isoallopregnanolone (Lundgren et al 2003;Stromberg et al 2006).…”

Section: Introductionmentioning

confidence: 91%

“…Allopregnanolone (3α-hydroxy-5α-pregnan-20-one) is one of the most potent and well known neuroactive steroids. However, its stereoisomer, isoallopregnanolone (3β-hydroxy-5α-pregnan-20-one), does not seem to have any effect on the GABA system by itself Stromberg et al 2006).…”

Section: Introductionmentioning

confidence: 99%

“…The only structural difference from its isomer allopregnanolone is the hydroxyl group in 3β-instead of 3α-position. Isoallopregnanolone by its own is, as far as we know today, without hormonal or GABA A receptor effects (Lundgren et al 2003;Stromberg et al 2006). Instead, isoallopregnanolone has often been used as a control when testing the specificity of allopregnanolone and its GABA A receptor enhancing effect, to show that the sterical configuration with the 3-hydroxy group is of major importance for the GABA A receptor stimulating effects of allopregnanolone (Gee et al 1987).…”

Section: Introductionmentioning

confidence: 99%

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Studies of pharmacokinetic and pharmacodynamic properties of isoallopregnanolone in healthy women

et al. 2008

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Rationale: The pharmacokinetics and behavioral effects of isoallopregnanolone (3β-hydoxy-5α-pregnan-20-one) in women are not known.Objectives: Allopregnanolone (3α-hydoxy-5α-pregnan-20-one) is a well known neurosteriod, acting via the GABA A receptor in the human brain. The naturally occurring progesterone metabolite isoallopregnanolone is the 3β-stereoisomer of allopregnanolone. Prior studies have concluded that isoallopregnanolone has no effect on the GABA A receptor. However, an antagonistic effect of isoallopregnanolone to allopregnanolone on the GABA A receptor has been shown in animal and in vitro studies. The purpose of this study was to evaluate the pharmacokinetics and behavioral effects of isoallopregnanolone in humans.Methods: Six healthy women were given three increasing doses of isoallopregnanolone intravenously in the follicular phase. Repeated blood samples for analyses of isoallopregnanolone and allopregnanolone concentrations were drawn. Saccadic eye movement variables, self rated sedation and mood rating scales were used during the test day.A Likert scale for prospective symptoms was used to measure daily fluctuations during the ongoing menstrual cycle.Results: Exogenously administered isoallopregnanolone produced a dose dependent increase in the serum concentration of isoallopregnanolone. In parallel there was also a rise in the allopregnanolone concentration. There was a decrease in saccade eye movement variables, but no effect was found on self-rated sedation or mood and no changes were seen in prospective symptoms during the menstrual cycle.Conclusions: After administration of isoallopregnanolone at a cumulative dose of 0.20 mg/kg, no adverse effects were observed. There is a metabolism of isoallopregnanolone to allopregnanolone, most likely explaining the effects on the saccadic eye movements.3

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Neurotransmitter, neurohormonal, and neuropeptidal function in stress and PTSD

Bremner

Pearce

2016

Posttraumatic Stress Disorder

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Neurosteroid modulation of allopregnanolone and GABA effect on the GABA-A receptor

Cited by 41 publications

References 45 publications

Allopregnanolone, a GABA_Areceptor agonist, decreases gonadotropin levels in women. A preliminary study

Allopregnanolone, a GABA_Areceptor agonist, decreases gonadotropin levels in women. A preliminary study

Studies of pharmacokinetic and pharmacodynamic properties of isoallopregnanolone in healthy women

Neurotransmitter, neurohormonal, and neuropeptidal function in stress and PTSD

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Neurosteroid modulation of allopregnanolone and GABA effect on the GABA-A receptor

Cited by 41 publications

References 45 publications

Allopregnanolone, a GABAAreceptor agonist, decreases gonadotropin levels in women. A preliminary study

Allopregnanolone, a GABAAreceptor agonist, decreases gonadotropin levels in women. A preliminary study

Studies of pharmacokinetic and pharmacodynamic properties of isoallopregnanolone in healthy women

Neurotransmitter, neurohormonal, and neuropeptidal function in stress and PTSD

Contact Info

Product

Resources

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Allopregnanolone, a GABA_Areceptor agonist, decreases gonadotropin levels in women. A preliminary study

Allopregnanolone, a GABA_Areceptor agonist, decreases gonadotropin levels in women. A preliminary study