Topic
Pregnenolone
About: Pregnenolone is a research topic. Over the lifetime, 3539 publications have been published within this topic receiving 126444 citations. The topic is also known as: (3b)-3-hydroxy-Pregn-5-en-20-one & 3-Hydroxypregn-5-en-20-one.
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TL;DR: The present data show that the loss of testicular LH and prolactin receptors induced by treatment with an LHRH agonist is accompanied by marked changes of the steroidogenic pathway, the defects being possibly located at the level of the 17-hydroxylase and 17,20-desmolase.
68 citations
TL;DR: Serum levels of allopregnanolone, pregnenolone sulfate, and dehydroepiandroster one sulfate were measured in 8 male patients with generalized anxiety disorder (GAD) and 8 healthy control subjects and suggest that patients with GAD have significantly lower levels of pregnenoline sulfate.
Abstract: Serum levels of allopregnanolone, pregnenolone sulfate, and dehydroepiandrosterone sulfate were measured in 8 male patients with generalized anxiety disorder (GAD) and 8 healthy control subjects Results suggest that patients with GAD have significantly lower levels of pregnenolone sulfate than control subjects
68 citations
TL;DR: The first report of the molecular genetic basis of 17 alpha-hydroxylase deficiency in a Southeast Asian patient is reported, with accurate demonstration that the patient was homozygous for this lesion, whereas one parent and two siblings were heterozygous.
Abstract: 17 alpha-Hydroxylase deficiency blocks the biosynthesis of cortisol and sex steroids, resulting in mineralocorticoid excess, hypertension, sexual infantilism, and female phenotype in both genetic sexes. The disease is caused by mutations in the gene encoding cytochrome P450c17, which is the single enzyme that mediates both 17 alpha-hydroxylase and 17,20-lyase activities. We report a 14-yr-old patient from Thailand with a classical clinical presentation of this rare disorder. Analysis of her P450c17 gene by polymerase chain reaction amplification and sequencing showed a nine-base deletion, eliminating codons 487-489 (Asp-Ser-Phe) near the carboxy-terminus of P450c17. This deletion creates a BclI site in the mutant DNA, permitting accurate demonstration that the patient was homozygous for this lesion, whereas one parent and two siblings were heterozygous. By use of site-directed mutagenesis, we created a vector that could express this mutated form of P450c17 when transfected into non-steroidogenic COS-1 cells. Such transfected cells produced immunodetectable P450c17 protein, but had no 17 alpha-hydroxylase or 17,20-lyase activity, whereas cells similarly transfected with a vector expressing normal human P450c17 could 17 alpha-hydroxylate either pregnenolone or progesterone and convert 17 alpha-hydroxypregnenolone to dehydroepiandrosterone, showing the presence of both activities. This is the first report of the molecular genetic basis of 17 alpha-hydroxylase deficiency in a Southeast Asian patient.
68 citations
TL;DR: The processes of final oocyte maturation and ovulation are both regulated by the maturation-inducing steroid, 17,20beta,21-trihydroxy-4-pregnen-3-one (20beta-S), which suggests that induction of ovulation is through a genomic mechanism of action, and potentially involves the previously characterized nuclear progestogen receptor.
68 citations
TL;DR: Estradiol was found to inhibit both activities of the purified enzyme with Δ 4 and with Δ 5 substrates (progesterone, pregnenolone, and the corresponding 17α-hydroxysteroids).
Abstract: Highly purified cytochrome P-450 from neonatal pig testicular rnicrosomes is capable of catalyzing both 17αhydroxylation and C-17,20-lyase activity. Estradiol was found to inhibit both activities of the purified enzyme with Δ 4 and with Δ 5 substrates (progesterone, pregnenolone, and the corresponding 17α-hydroxysteroids). For the Δ 4 series, inhibition of lyase is competitive and that of 17α-hydroxylase is noncompetitive; for the Δ 5 series, inhibition was noncompetitive for both activities. Ki values for lyase activity were determined from enzyme kinetics (5.0 μM for the Δ 4 substrate and 20 μM for the Δ 55 substrate). Estradiol produces a typical type I spectral shift with the pure enzyme (Ks = 3.0 μ where Ks is the concentration of steroid required to give half maximal spectral shift), so that Ki values were also determined directly from binding studies by using substrate-induced difference spectroscopy. Fifty per cent inhibition of the maximal spectral shift induced by the 17α-hydroxysubstrates (Ki) ...
68 citations