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.

Serum concentrations of some neuroactive steroids in women suffering from mixed anxiety-depressive disorder.

Abstract: Concentrations of neurosteroids may be influenced by some physiological or pathological factors. We investigated neuroactive steroids in the serum of women suffering from anxiety-depressive disorder treated with fluoxetine and in a control group, in both the follicular and the luteal phases of the menstrual cycle. Two groups of neuroactive steroids were measured by radioimmunoassays: 1) the positive allosteric modulator of GABAA receptors, allopregnanolone with its precursor progesterone and 2) pregnenolone sulfate and dehydroepiandrosterone sulfate (DHEAS) acting on GABAA receptors by an opposite mechanism. Significantly higher levels of pregnenolone sulfate (p < 0.0001) were found in patients in both phases of the menstrual cycle. Significantly higher values were recorded in pregnenolone (p < 0.001) and 17α-hydroxy-pregnenolone (p < 0.01) levels in the patients group in the follicular phase. Our results indicate that imbalance in neuroactive steroids may play a negative role in origin and course of psychiatric and neurological disorders.

Antisteroidogenic actions of hydrogen peroxide on rat Leydig cells.

Abstract: It has been well known that reactive oxygen species (ROS) are produced in the steroidogenic pathway and spermatozoa. H 2 O 2 , one of ROS produced by spermatozoa, appears to be a primary toxic agent. In the present study, we examined the effects of H 2 O 2 on the basal and evoked-testosterone release from primary Leydig cells, the protein expressions of cytochrome P450 side chain cleavage enzyme (P450scc) and steroidogenic acute regulatory (StAR) protein were also investigated. Our preparation was found to contain approximately 87% Leydig cells and very few macrophages. The results demonstrated that H 2 O 2 (>1 x 10 4 M) significantly inhibited the basal and hCG-stimulated testosterone release. H 2 O 2 abolished forskolin- or 8-Br-cAMP-evoked testosterone release. In the presence of pregnenolone, progesterone, or androstenedione, the inhibitory effect of H 2 O 2 on testosterone release was prevented. H 2 O 2 also inhibited pregnenolone production in the presence of trilostane (an inhibitor of 3β-hydroxysteroid dehydrogenase), therefore diminished the activity of P450scc in Leydig cells. In addition to the inhibition of hormone secretion, H 2 O 2 also regulated steroidogenesis by diminishing protein expression of StAR. These results suggest that H 2 O 2 acts directly on rat Leydig cells to diminish testosterone production by inhibiting P450scc activity and StAR protein expression.

A Novel Homozygous Mutation in CYP11A1 Gene Is Associated with Late-Onset Adrenal Insufficiency and Hypospadias in a 46,XY Patient

Abstract: Context: The first and the rate-limiting step in the biosynthesis of hormones in all steroidogenic tissues, conversion of cholesterol to pregnenolone, is catalyzed by the cholesterol side-change cleavage cytochrome P450 (P450scc) encoded by a single gene, CYP11A1. To date, mutations in CYP11A1 gene have been reported in six patients, all of whom presented with adrenal insufficiency within the first 4 yr of life and severely underandrogenized external genitalia (Prader stages 1–2). Objective: Our aim was to characterize in vitro and in vivo effects of a novel homozygous CYP11A1 gene mutation identified in a patient with an unusual presentation of P450scc deficiency. Methods and Patients: A 46,XY patient presented with mid-shaft hypospadias and cryptorchidism at birth and signs of adrenal failure at 9 yr. Mutational analysis of CYP11A1 gene was performed by PCR, followed by direct sequencing. P450scc activity was determined by measuring concentration of pregnenolone synthesized from cholesterol in the mediu...