Neuroactive steroids, their precursors and polar conjugates during parturition and postpartum in maternal blood: 2. Time profiles of pregnanolone isomers

Hill, Martin; Bičı́ková, Marie; Pařı́zek, Antonı́n; Havlı́ková, Helena; Klak, Jan; Fajt, T.; Meloun, Milan; Cibula, David; Cegan, Alexander; Šulcová, J; Hampl, Richard; Stárka, L.

doi:10.1016/s0960-0760(01)00073-5

Cited by 29 publications

(26 citation statements)

References 22 publications

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“…The levels of free PIs obtained in this study are comparable with the previously published data [20,26]. The concentrations of conjugates obtained here are however higher.…”

Section: Discussionsupporting

confidence: 91%

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Circulating levels of pregnanolone isomers during the third trimester of human pregnancy

Hill

Cibula

Havlı́ková

et al. 2007

The Journal of Steroid Biochemistry and Molecular Biology

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“…The levels of free PIs obtained in this study are comparable with the previously published data [20,26]. The concentrations of conjugates obtained here are however higher.…”

Section: Discussionsupporting

confidence: 91%

“…Although several studies have brought information to light regarding the profiles of unconjugated PIs in maternal and umbilical blood [19][20][21][22][23][24][25], only a small number have included data regarding the respective polar conjugates [19,20,26].…”

Section: Introductionmentioning

confidence: 99%

Circulating levels of pregnanolone isomers during the third trimester of human pregnancy

Hill

Cibula

Havlı́ková

et al. 2007

The Journal of Steroid Biochemistry and Molecular Biology

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“…This concentration is similar to that found during third-trimester pregnancy (Hill et al , 2001Luisi et al 2000;Parizek et al 2005); it produced significant effects in objective and subjective measures of sedation. Given the pronounced effect of acutely administered allopregnanolone found in this study, it is conceivable that a gradual tolerance to the sedative effects of allopregnanolone occurs during pregnancy.…”

Section: Discussionsupporting

confidence: 80%

“…Plasma concentrations of allopregnanolone temporally follow those of progesterone, and levels of approximately 6-10 nmol L −1 have been found in the mid-luteal phase of the menstrual cycle (Genazzani et al 1998;Wang et al 1996), and during third-trimester pregnancy, allopregnanolone levels up to 150 nmol L −1 have been found in maternal blood and umbilical cord blood (Hill et al , 2001Luisi et al 2000;Parizek et al 2005).…”

Section: Introductionmentioning

confidence: 92%

Pharmacokinetic and behavioral effects of allopregnanolone in healthy women

et al. 2005

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Abstract.Rationale. The behavioral effects of allopregnanolone (3-hydroxy-5-pregnan-20-one) in women are not known. Objective: Allopregnanolone, a neuroactive steroid secreted by the mammalian ovary, exerts its anesthetic, anxiolytic, and sedative/hypnotic effects through potentiation of GABA A receptors. The purpose of this study was to evaluate the behavioral effects of allopregnanolone in healthy women. Methods: Ten healthy women were given three increasing intravenous doses of allopregnanolone in the follicular phase of the menstrual cycle. Saccadic eye movement parameters and visual analogue scales of sedation were used to evaluate the behavioral response of allopregnanolone. Repeated blood samples for analyses of allopregnanolone were drawn throughout the study day. Results:Exogenously administered allopregnanolone decreases saccadic eye movement parameters and increases subjective ratings of sedation that correlate with increased serum concentrations of this neuroactive steroid. Conclusion: The behavioral effects of allopregnanolone are similar to that of its 5-stereoisomer, pregnanolone (3-hydroxy-5 -pregnan-20-one). Apart from fatigue and mild nausea, allopregnanolone given in a cumulative dose of 0.09 mg/kg did not have any adverse effects.

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“…During the third trimester of pregnancy, plasma levels of pregnanolone and ALLO are about 50-100 nmol/L Hill et al 2001). Already 1 h after parturition, maternal serum ALLO decreases significantly, whereas pregnanolone serum concentration does not decrease until 1 day after parturition (Hill et al 2001).…”

Section: Introductionmentioning

confidence: 99%

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

2005

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Neuroactive steroids are a large group of substances having effect in the brain and on brain function. The steroids most studied are allopregnanolone (ALLO), tetrahydrodesoxycorticosterone (THDOC), pregnenolone sulfate (PS) dihydroepiandrosteronesulfate (DHEAS), and estradiol (E2). ALLO and THDOC are called gamma-aminobutyric acid (GABA) steroids as they are positive modulators of the GABAA receptor in a similar way as benzodiazepines, barbiturates, and alcohol. GABA steroids not only have similar behavioral effects as benzodiazepines and barbiturates but, possibly, also similar adverse effects as well. This review aims to elucidate the possible role that neuroactive steroids play in the development of mood disorders in women. One of the most clear-cut examples of the interaction between mood, neuroactive steroids, and the GABA system is premenstrual dysphoric disorder (PMDD), which is a cluster of negative mood symptoms occurring during the luteal phase of the menstrual cycle in 2-6% of reproductive women. Furthermore, certain women also experience adverse mood effects during sequential progestin addition to postmenopausal estrogen treatment, which is why the role of neuroactive steroids in postmenopausal women is also addressed in this review.

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Neuroactive steroids, their precursors and polar conjugates during parturition and postpartum in maternal blood: 2. Time profiles of pregnanolone isomers

Cited by 29 publications

References 22 publications

Circulating levels of pregnanolone isomers during the third trimester of human pregnancy

Circulating levels of pregnanolone isomers during the third trimester of human pregnancy

Pharmacokinetic and behavioral effects of allopregnanolone in healthy women

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

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