Identification and quantitation of 5α-pregnanedione in human pregnancy plasma

Støa, K. F.; Bessesen, Atle

doi:10.1016/0022-4731(75)90024-2

Cited by 32 publications

(12 citation statements)

References 7 publications

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“…Hill and colleagues [44] and Parizek and associates [30] reported values in the range of 18-25 nmol/l near term, which is compatible with our value of 17.05 + 10.2 nmol/l at 36-38 weeks. PROG was the most abundant steroid during pregnancy, and our levels generally agree with published reports throughout pregnancy [26,[28][29][30]. 5a-DHP was the second most abundant steroid, and also increased significantly with gestational age.…”

Section: Discussionsupporting

confidence: 94%

“…Prenatal PROG synthesis increases dramatically with gestational age, dropping sharply following parturition, and ALLO appears to follow this trend also [26][27][28][29][30]. During pregnancy, because elevating circulating ALLO may freely cross the blood-brain barrier, homeostatic adaptations must occur to maintain stability in brain GABA A function.…”

Section: Introductionmentioning

confidence: 99%

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3α-reduced neuroactive steroids and their precursors during pregnancy and the postpartum period

Evans

Ross

Sellers

et al. 2005

Gynecological Endocrinology

103

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Allopregnanolone (ALLO) and pregnanolone (PREG), the 3alpha-reduced metabolites of progesterone (PROG), are potent modulators of gamma-aminobutyric acid type A receptors that may function as endogenous anxiolytics. They are purported to be involved in the etiology or expression of clinical depression. In the present study we quantified ALLO and PREG, as well as PROG, 5alpha-dihydroprogesterone (5alpha-DHP), 5beta-dihydroprogesterone (5beta-DHP), epiallopregnanolone and pregnenolone (PREGNEN), in plasma from healthy women at five time points during pregnancy and the postpartum period. Analysis was by gas chromatography/electron capture - negative chemical ionization - mass spectrometry. Neuroactive steroids increased significantly from 10 to 36 weeks of pregnancy, except for 5beta-DHP and PREGNEN which did not change significantly. PROG was the most abundant steroid throughout pregnancy, followed by 5alpha-DHP and ALLO. Metabolite to precursor ratios differed depending on the enzyme and substrate: the turnover of PROG to 5alpha-DHP (catalyzed by 5alpha-reductase) was stable while the conversion of PROG to 5beta-DHP (catalyzed by 5beta-reductase) decreased later in pregnancy. 3alpha-Hydroxysteroid oxidoreductase-mediated turnover of 5alpha- and 5beta-DHP to their metabolites ALLO and PREG, respectively, rose during pregnancy, but the turnover of 5alpha-DHP to ALLO dropped at the late prenatal visit. At 6 weeks postpartum all steroids were significantly reduced compared with late prenatal values, with 5alpha-DHP being the most abundant postpartum steroid. These results provide the basis for further study of neuroactive steroids in psychiatric conditions of pregnancy and the postpartum period.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

3α-reduced neuroactive steroids and their precursors during pregnancy and the postpartum period

Evans

Ross

Sellers

et al. 2005

Gynecological Endocrinology

103

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“…This includes, and to the best of our knowledge is the first report of, allopregnanolone concentrations in mares. DHP and allopregnanolone reached concentrations comparable with those seen in the third trimester of human pregnancy (Milewich et al 1975, Stoa & Bessesen 1975, Hill et al 2007. Though 6-to 20-fold higher concentrations (120 to O400 ng/ml) may be required to induce signs of anesthesia (Madigan et al 2012), those observed in pregnant mares are well within concentrations observed in patients reacting to panicinducing stimuli (Eser et al 2006).…”

Section: Discussionmentioning

confidence: 48%

The dynamic steroid landscape of equine pregnancy mapped by mass spectrometry

Legacki¹,

Scholtz²,

Ball³

et al. 2016

Reproduction

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Liquid chromatography-tandem mass spectrometry (LC-MS/MS) allowed comprehensive analysis of various steroids detectable in plasma throughout equine gestation. Mares (nZ9) were bled serially until they foaled. Certain steroids dominated the profile at different stages of gestation, clearly defining key physiological and developmental transitions. The period (weeks 6-20) coincident with equine chorionic gonadotropic (eCG) stimulation of primary corpora lutea and subsequent formation of secondary luteal structures was defined by increased progesterone, 17OH-progesterone and androstenedione, all D4 steroids. The 5a-reduced metabolite of progesterone, dihydroprogesterone (DHP) paralleled progesterone secretion at less than half the concentration until week 12 of gestation when progesterone began to decline but DHP concentrations continued to increase. DHP exceeded progesterone concentrations by week 16, clearly defining the luteo-placental shift in pregnane synthesis from primarily ovarian to primarily placental. The period corresponding to the growth of fetal gonads was defined by increasing dehydroepiandrosterone and pregnenolone (D5 steroids) concentrations from week 14, peaking at week 34 and declining to term. Metabolites of DHP (including allopregnanolone) dominated the steroid profile in late gestation, some exceeding DHP by weeks 13 or 14 and near term by almost tenfold. Thus D4 steroids dominated during ovarian stimulation by eCG, inversion of the ratio of progesterone: DHP (increasing 5a-pregnanes) marked the luteo-placental shift, D5 steroids defined fetal gonadal growth and 5a-reduced metabolites of DHP dominated the steroid profile in mid-to late-gestation. Comprehensive LC-MS/MS steroid analysis provides opportunities to better monitor the physiology and the progress of equine pregnancies, including fetal development.

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“…Though increasing steadily throughout pregnancy, concentrations of allopregnanolone in the plasma of pregnant mares remain less than 20 ng/mL [143,196] (Fig. 4), comparable with those seen in third trimester human pregnancies [144][145][146]. Such concentrations are low, and as much as 6-to 20-fold higher concentrations are likely required to induce somnolence on the basis of studies in foals [147].…”

Section: The Feto-placental Unitmentioning

confidence: 74%

Review of the reproductive endocrinology of the pregnant and parturient mare

Conley

2016

Theriogenology

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Identification and quantitation of 5α-pregnanedione in human pregnancy plasma

Cited by 32 publications

References 7 publications

3α-reduced neuroactive steroids and their precursors during pregnancy and the postpartum period

3α-reduced neuroactive steroids and their precursors during pregnancy and the postpartum period

The dynamic steroid landscape of equine pregnancy mapped by mass spectrometry

Review of the reproductive endocrinology of the pregnant and parturient mare

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