High impact information on pregnenolone

• However, PROG, although it binds to MAP2, does not increase the immunostaining of MAP2, contrary to PREG and MePREG [1].
• Nocodazole, a microtubule-disrupting agent, induces a major retraction of neurites in control cultures, but pretreatment with PREG/MePREG is protective [1].
• The levels of all of the C-19 steroids measured decreased clearly between weeks 14-20 of gestation, whereas those of the C-21 steroids, P5, progesterone, and 17-hydroxyprogesterone, remained relatively high [2].
• Our results suggest that the metabolic reactions converting P5 to androgens are activated in the human fetal testis within a short time range between 8-11 weeks of gestation [2].
• Trilostane, a competitive inhibitor of the 3beta-HSD caused a potent inhibition of the rate of conversion of PREG to PROG (IC50 = 4.06 +/- 2.58 microm) [3].

Biological context of pregnenolone

• Decreasing MAP2 expression by RNA interference does not modify PROG action, but it prevents the stimulatory effects of PREG and MePREG on neurite extension, showing that MAP2 is their specific receptor [1].
• Significantly higher levels of pregnenolone sulfate (p < 0.0001) were found in patients in both phases of the menstrual cycle [4].
• Follicles collected 12h after the first injection to induce ovulation were incubated with radioinert pregnenolone (P5) or tritiated-P5 ([3H]P5) plus radioinert P5 [5].

Anatomical context of pregnenolone

• By comparing the ability of each cell type in the production of neurosteroids, astrocytes are the major producer of P4, DHEA, and androgens, whereas oligodendrocytes are predominantly the producer of P5 and neurons of estrogens [6].
• We estimated the activities of the cholesterol side-chain cleavage (P450scc) enzyme (which is a key enzyme involved in the conversion of cholesterol to P5) and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) (which catalyses the conversion of P5 to P4) in the luteal cells treated with different doses of antide [7].
• Of the PEs measured, maximum serum levels of PE, 3 beta,17 alpha-hydroxy-5-pregnen-20-one (17-PE) and 3 beta,17 alpha, 20 beta-dihydroxy-5-pregnene (17,20-PE) were found during later oocytes stages associated with germinal vesicle breakdown [8].
• Pregnenolone (PREG) and corticosterone were measured in sciatic nerves and plasma of adult male rats by radioimmunoassays [9].

Associations of pregnenolone with other chemical compounds

• This study extended that work to measure the integrated response on production of testosterone (T), estradiol (E2), and progesterone/pregnenolone (P) using an ELISA [10].
• DHEA/17-OH-Preg and Delta4A/17-OHP ratios, reflecting 17,20-lyase activity, were low before treatment and recovered to the normal range after treatment, and 17-OH-Preg/Preg and 17-OHP/Prog ratios, reflecting 17-hydroxylase activity, were high before treatment, and fell within the normal range after treatment [11].
• The principal conclusions are that T, 5 beta-T and the PEs can be considered as MISs in winter flounder and the PE pathway predominates during the final stages of oocyte maturation in winter flounder in contrast to progesterones which predominate in other fish species, mostly salmonids, studies to date [8].
• We examined the concentrations of Preg, 17-OH-Preg, DHEA, androstenediol (ADIOL) and their sulfates in whole brains from DBA/2, C57BL/6, BALB/c, ddY and ICR mice, the genetic backgrounds of which are different [12].
• The DHEA-S/delta 4A ratio increased more than five times over the basal ratio, and P5/P and 17 alpha-hydroxypregnenolone (17-OHP5)/17-OHP ratios did not increase after adrenocorticotrophic hormone ACTH stimulation [13].

Gene context of pregnenolone

• PAP seemed the more pathological marker; PSA was somewhat anticorrelated to the adrenal androgen (DHA and DS) and PREG levels [14].
• DHEA, PREG and their sulphate derivatives on plasma and brain after CRH and ACTH administration [15].
• In addition, the expressions of StAR protein and P450scc enzyme were not significantly different between hCG alone and hCG plus amphetamine treatment in MA-10 cells (p > 0.05) [16].
• Progesterone and PREGS also bind to MAP2, but counteract PREG activity [17].
• It catalyzes the reaction of 17alpha-hydroxylation of progesterone (P4) and pregnenolone (P5) and the 17,20-lyase reaction resulting in side chain cleavage of C21 steroids to form C19 steroids [18].

Analytical, diagnostic and therapeutic context of pregnenolone

• After combined adrenalectomy and gonadectomy, significant levels of PREG and PROG remained in the SC, suggesting their local biosynthesis [19].
• The activity of 3beta-HSD in homogenates was evaluated using 3H-labelled PREG as a substrate and NAD+ as a cofactor, the levels of steroids formed were calculated either by extrapolating the relationship between tritiated peaks obtained by TLC to the initial amount of PREG, or by gas chromatography/mass spectrometry determination [3].
• Levels of steroids formed were calculated either by extrapolation of the relationship between the tritiated peaks obtained by thin layer chromatography (TLC) and the initial amount of PREG, or by gas chromatography-mass spectrometry (GC-MS) determination [20].

References