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

This study addresses the question of whether changes in the biosynthesis and metabolism of neuroactive pregnanolone isomers (PIs) might participate in the timing of parturition in humans. The time profiles of unconjugated allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one, P3alpha5alpha), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one, P3alpha5beta), isopregnanolone (3beta-hydroxy-5alpha-pregnan-20-one, P3beta5alpha) and epipregnanolone (3beta-hydroxy-5beta-pregnan-20-one, P3beta5beta), pregnenolone, their polar conjugates, progesterone, 5alpha-dihydroprogesterone (P5alpha), and 5beta-dihydroprogesterone (P5beta) were monitored in the plasma of 30 healthy women during the third trimester of pregnancy, at 1-week intervals from the 30th week of gestation using GC-MS. Changes in the steroid levels were evaluated by two-way ANOVA with gestational age and subject as independent factors.

Serum profiles of free and conjugated neuroactive pregnanolone isomers in nonpregnant women of fertile age.

Background: Pregnanolone isomers (PI) with a hydroxy group in the 3alpha-position are neuroinhibitors operating via positive modulation of GABA(A) receptors. The 3beta-PI and sulfates of PI and pregnenolone exert the opposite effect. In addition to the brain's in situ synthesis, some circulating steroids can penetrate the blood-brain barrier.

Syntheses of 19-[O-(carboxymethyl)oxime] haptens of epipregnanolone and pregnanolone.

O-(Carboxymethyl)oximes 1 and 2 derived from two epimeric 5beta-pregnanolones (3beta-hydroxy-5beta-pregnan-20-one and 3alpha-hydroxy-5beta-pregnan-20-one) in position 19 were prepared. Two synthetic routes were employed, both using protection of the 20-keto group after reduction into the (20R)-alcohol in the form of acetate. In the first route, (20R)-19-hydroxy-5beta-pregnan-3beta,20-diyl diacetate (3) was transformed into the corresponding 19-[O-(carboxymethyl)oxime] methyl ester 6, then deacetylated by acid and partially silylated with tert-butyldimethylsilyl chloride.

Reinstatement of serum pregnanolone isomers and progesterone during alcohol detoxification therapy in premenopausal women.

Background: Alcohol abuse is associated with menstrual irregularities related to the inhibition of progesterone secretion involved in regulation of the menstrual cycle. Reduced progesterone metabolites, including pregnanolone isomers (PIs), are efficient neuromodulators. The authors attempted to evaluate whether levels of PIs reflect impairment in progesterone biosynthesis in premenopausal women treated for alcohol addiction and whether alcohol detoxification therapy contributes to the restoration of their reproductive functions and psychosomatic stability by influencing steroid biosynthesis.

The identification and simultaneous quantification of 7-hydroxylated metabolites of pregnenolone, dehydroepiandrosterone, 3beta,17beta-androstenediol, and testosterone in human serum using gas chromatography-mass spectrometry.

7-Hydroxy-metabolites of dehydroepiandrosterone (DHEA) and 3beta,17beta-androstenediol (AD) possess immunomodulatory and neuroprotective properties; therefore, the measurement of these steroids in patients with autoimmune diseases or disturbances in the CNS may be of interest. A gas chromatography-mass spectrometry (GC-MS) method for the determination of 7-hydroxy-metabolites of pregnenolone, DHEA, AD, and testosterone including the parent steroids was applied to serum samples from 12 adult men (27-66 years), 13 male adolescents (13-20 years), 5 boys (6-10 years), 15 women in the follicular phase of the menstrual cycle (22-45 years), 17 women in the luteal phase (22-45 years), and 4 girls (6-10 years). The steroids were age and sex dependent, but independent of the menstrual cycle.

Altered profiles of serum neuroactive steroids in premenopausal women treated for alcohol addiction.

Long-term alcohol consumption results in menstrual irregularities due to the inhibition of progesterone secretion. Some progesterone metabolites, including three pregnanolone isomers (PI), abate, while pregnenolone sulfate (PregS) and dehydroepiandrosterone sulfate (DHEAS) increase, alcohol tolerance. The rationale of this study was to evaluate how the neuroactive steroids reflect the impaired progesterone formation in premenopausal women treated for alcohol addiction, and whether detoxification therapy could restore female reproductive functions and psychosomatic stability by reinstatement of the steroid biosynthesis.

Neuroactive pregnanolone isomers during pregnancy.

The pregnanolone isomers (PI) allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one), isopregnanolone (3beta-hydroxy-5alpha-pregnan-20-one), epipregnanolone (3beta-hydroxy-5beta-pregnan-20-one), progesterone, and estradiol were measured in 138 pregnant women. The sampling was carried out from the first through the 10th month of pregnancy. Gas chromatography-mass spectrometry analysis and RIA were used for the measurement of steroid levels.

Plasma levels of 7-hydroxylated dehydroepiandrosterone (DHEA) metabolites and selected amino-thiols as discriminatory tools of Alzheimer's disease and vascular dementia.

Objective: The early differential diagnosis of Alzheimer's disease (AD) remains still problematic. We developed a laboratory test enabling us to distinguish patients with AD from those with vascular dementia (VD) and healthy subjects.

Methods: The AD group consisted of 22 women and 18 men.

Sex- and age-related changes in epitestosterone in relation to pregnenolone sulfate and testosterone in normal subjects.

Epitestosterone has been demonstrated to act at various levels as a weak antiandrogen. So far, its serum levels have been followed up only in males. Epitestosterone and its major circulating precursor pregnenolone sulfate and T were measured in serum from 211 healthy women and 386 men to find out whether serum concentrations of epitestosterone are sufficient to exert its antiandrogenic actions.