scispace - formally typeset
Search or ask a question
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.


Papers
More filters
Journal ArticleDOI
TL;DR: It is concluded that the cytochrome P-450 C21 side-chain cleavage enzyme from pig testicular microsomes is also capable of synthesizing delta 16-C19-steroids and is, therefore, likely to be responsible for the large amounts of the pherormone androstadienone produced by male pigs.

64 citations

Journal ArticleDOI
TL;DR: The influence of membrane cholesterol on some pharmacological properties of the GABAA receptor was investigated in acutely dissociated rat hippocampal neurones with whole cell patch clamp recording and effects on the non‐steroidal potentiators of GABA of cholesterol‐enrichment or addition of epicholesterol to the neurones are suggested to be due to changes in membrane fluidity.
Abstract: 1. The influence of membrane cholesterol on some pharmacological properties of the GABA(A) receptor was investigated in acutely dissociated rat hippocampal neurones with whole cell patch clamp recording. The cholesterol levels were varied between 56% and 235% control using methyl-beta-cyclodextrin as the cholesterol carrier. 2. Enrichment of neurones with cholesterol increased the effects of the non-steroidal GABA potentiators propofol, flunitrazepam and pentobarbitone. A similar result was obtained after pre-incubation of neurones with epicholesterol, the 3alpha-hydroxy isomer of cholesterol. 3. In contrast, the effects of the steroidal GABA potentiators pregnanolone and alfaxalone were reduced by cholesterol enrichment, but not by epicholesterol. Depletion of membrane cholesterol increased the potentiation of GABA by pregnanolone and alfaxalone but did not affect the non-steroidal potentiators. 4. The steroidal antagonist of GABA, pregnenolone sulphate, reduced the maximum response to GABA. This effect, also, was diminished in cholesterol-enriched neurones and enhanced in cholesterol-depleted neurones. 5. The effects of the cholesterol manipulations that were selective for the steroidal modulators of GABA are suggested to arise from direct interactions between membrane cholesterol and the GABA(A) receptor. The separate effects on the non-steroidal potentiators of GABA of cholesterol-enrichment or addition of epicholesterol to the neurones are suggested to be due to changes in membrane fluidity. 6. In view of the likely physiological modulation of GABA(A) receptors by endogenous neuroactive steroids and evidence of the in vivo lability of membrane cholesterol, the present observations may have physiological as well as pharmacological relevance.

63 citations

Journal ArticleDOI
TL;DR: Findings converge to suggest that progesterone derivative neurosteroids such as allopregnanolone and allotetrahydrodeoxycorticosterone have significant mood-stabilizing effect, consistent with the observation that a number of anticonvulsants are effective therapies for bipolar disorder.
Abstract: Neurosteroids are synthesized in the brain and modulate brain excitability. There is increasing evidence of their sedative, anesthetic and antiseizure properties, as well as their influence on mood. Currently neurosteroids are classified as pregnane neurosteroids (allopregnanolone and allotetrahydrodeoxycorticosterone), androstane neurosteroids (androstanediol and etiocholanone) or sulfated neurosteroids (pregnenolone sulfate and dehydroepiandrosterone sulfate). Both preclinical and clinical findings indicate that progesterone derivative neurosteroids such as allopregnanolone and allotetrahydrodeoxycorticosterone play a role in mood disorders. Clozapine and olanzapine, which were shown to be effective in stabilizing bipolar disorder, elevate pregnenolone levels in rat hippocampus, cerebral cortex, and serum. In lithium-treated mice, the blood levels of allopregnanolone and pregnenolone were elevated compared to control levels. Women diagnosed with bipolar disorder typically show symptomatic exacerbation in relation to the menstrual cycle, and show vulnerability to the onset or recurrence of mood disorders immediately after giving birth, when the levels of neurosteroid derivatives of progesterone drop. Whereas in women who had recovered from bipolar disorder, the plasma concentration of allopregnanolone was elevated compared to either healthy controls or women with major depressive disorder during the premenstrual period. During depressive episodes, blood level of allopregnanolone is low. Treatment with fluoxetine tends to stabilize the levels of neurosteroids in depression. These findings converge to suggest that these steroids have significant mood-stabilizing effect. This hypothesis is consistent with the observation that a number of anticonvulsants are effective therapies for bipolar disorder, a finding also consistent with the antiseizure properties of neurosteroids. Further exploration of action of neuroactive steroids is likely to open new frontiers in the investigation of the etiology and treatment of mood disorders, particularly bipolar disorders.

63 citations

Journal ArticleDOI
TL;DR: The hypothesis that human adrenal androgen synthesis does not require a special hormone is supported, because low 3 beta-hydroxysteroid dehydrogenase activity is an intrinsic cell property.
Abstract: The activities of 3β-hydroxysteroid dehydro-genase, 17-hydroxylase, 21-hydroxylase, 11β-hydroxylase, C17,2o-lyase, and dehydroepiandrosterone sulfotransferase were measured in cultured human fetal definitive zone adrenocortical cells with and without prior exposure to 1 eM ACTH for 48 h. Enzyme induction and measurements of activity were performed using serum- and lipoprotein-free conditions. ACTH induced increases of 5- to 100-fold in the activity of all of these enzymes. Although 3β-hydroxysteroid dehydrogenase activity was increased 15-fold, its activity was still an order of magnitude less than that of the hydroxylases. In contrast, when similar experiments were performed using bovine adrenocortical cells, 3β-hydroxysteroid dehydrogenase activity was similar to that of the hydroxylases after induction with ACTH. The lower activity of 3β-hydroxysteroid dehydrogenase in human cells compared to that in bovine cells resulted in different sequences of transformation of [3H]pregnenolone. The initial product...

63 citations


Network Information
Related Topics (5)
Hormone
38.3K papers, 1.2M citations
88% related
Estrogen
40.7K papers, 1.7M citations
87% related
Estrogen receptor
34.2K papers, 1.4M citations
82% related
Receptor
159.3K papers, 8.2M citations
80% related
Secretion
24.8K papers, 1.2M citations
79% related
Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202344
202255
202124
202028
201950
201835