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.

Developmental Pattern of Testosterone Synthesis in the Fetal Gonad of the Rabbit

Abstract: Two aspects of testosterone formation by the fetal testes have been investigated in rabbit embryos and newborn that varied in age from 17 days of gestation to 3 days after birth. In the first series of studies the placental content of pregnenolone and progesterone was measured by a double isotope derivative technique. At each time studied the concentration of pregnenolone (mean 12.0 ng/g) exceeded that of progesterone (mean 2.5 ng/g). This finding indicates that C21 steroids of placental origin are available to serve as potential precursors for testosterone biosynthesis by the fetal testis prior to the commencement of this function. In the second series of studies the conversion of pregnenolone-7α-3H to testosterone by the fetal gonad was investigated, utilizing thin—layer and Celite column chromatography for the separation of the incubation products. The capacity for testosterone formation from this precursor was shown to rise from immeasurably low levels at day 17 to a maximal rate of 344 pmoles/10 mg t...

The development of placental androstenedione and testosterone production and their utilization by the ovary for aromatization to estrogen during rat pregnancy.

Abstract: During rat pregnancy the placenta may provide androgens as a source of precursor for estradiol (E2) formation by the ovary. However, the relative importance of testosterone (T) and delta 4-androstenedione (delta 4 A) for ovarian E2 production is unknown. The present study therefore determined the ability of the rat placenta to convert [3H] pregnenolone (P5) substrate to [3H] delta 4 A and [3H] T, and to [3H] progesterone (P4) in vitro on Days 12, 14, 16 and 18 of gestation. The placental formation of delta 4 A and T was correlated with the uterine vein and peripheral sera concentrations of both androgens, and with their ability to be aromatized to E2 in vitro by the ovary. Placental androgen formation from P5 increased and formation of P4 decreased with advancing gestation, with the formation of delta 4 A being approximately 2- to 4-fold greater (P less than 0.01) than the formation of T on Days 12 to 16 of gestation. The conversion of P5 to delta 4 A increased (P less than 0.001) from 18 +/- 0.9 (mean percent conversion +/- SEM) on Day 12 to 53 +/- 3 and 57 +/- 4 on Days 14 and 16, respectively, then decreased (P less than 0.05) to 42 +/- 2 on Day 18. The uterine vein and peripheral sera concentrations of delta 4 A were 2- and 3-fold greater (P less than 0.05-0.001) than T, respectively, on Days 12 to 16.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection in bovine adrenal cortex of a lipoidal substance that yields pregnenolone upon treatment with alkali

Abstract: Bovine adrenal cortical tissue contains a lipoidal derivative of pregnenolone (3beta-hydroxy-pregn-5-en-20-one) from which the free steroid can be liberated by treatment with alkali. Evidence for the presence of such an entity comes from examination of a nonpolar extract of tissue from which pregnenolone and its sulfate had been removed by chromatography. Treatment of the nonpolar fraction with alkali followed by exhaustive chromatographic analysis led to the detection of pregnenolone. The steroid was identified by both gas chromatography/mass spectrometry and double isotope procedures. Quantitative analysis indicated that the three forms of pregnenolone are present in bovine adrenal cortical tissue in the following amounts (mug/kg): lipoidal derivative, 290; free steroid, 435; and sulfate, 65. Because the only known metabolic function of pregnenolone is to serve as a precursor of the steroid hormones, these findings have far-reaching implications for steroid hormone biochemistry.

Pregnenolone protects mouse hippocampal (HT-22) cells against glutamate and amyloid beta protein toxicity

Abstract: In the present work we have examined whether the neurosteroid pregnenolone has any neuroprotective effects against glutamate and amyloid beta protein neurotoxicity using immortalized clonal mouse hippocampal cell line (HT-22). The neurosteroid pregnenolone protects HT-22 cells against both 5 mM glutamate and 2 μM amyloid beta protein induced cell death in a concentration dependent manner. Optimum protection was attained at 500 nM pregnenolone, against both 5 mM glutamate as well as 2 μM amyloid beta protein induced HT-22 cell death. Furthermore, using confocal immunoflourescence microscopy we observed that 20 hours of treatment with 5 mM glutamate resulted in intense nuclear localization of the glucocorticoid receptor (GR) in HT-22 cells as compared to control untreated cells. Interestingly, 500 nM pregnenolone treatment for 24 hours, followed by 20 hours treatment with 5 mM glutamate resulted in dramatic reduction in GR nuclear localization. These results show that (i) pregnenolone has neuroprotective effects against both glutamate and amyloid beta protein neuropathology and (ii) prevention of glucocorticoid receptor (GR) localization to the nucleus may be involved in the observed neuroprotective effects of pregnenolone against glutamate neurotoxicity.

Effects of steroids on mouse oocyte maturation in vitro.

Abstract: Oestrone and dihydrotestosterone had no significant action. Other steroids inhibited maturation. The stage of maturation most affected and the median effective concentration (MEC) at this stage varied with different steroids. The predominant effect of pregnenolone (MEC = 6.4 microM), progesterone (MEC = 5.3 microM), androstenedione (MEC = 28.0 microM) and oestradiol-17 beta (MEC = 23.0 microM) was to block maturation after the resumption of meiosis but before completion of the first meiotic division. Testosterone was also effective at this stage (MEC = 23.5 microM) but at higher concentrations it prevented germinal vesicle breakdown (MEC = 40 microM) without causing oocyte degeneration. The inhibitory actions of all steroids were reversible in oocytes exposed for 4 or 18 h.