Pregnenolone: A 21-carbon steroid, derived from CHOLESTEROL and found in steroid hormone-producing tissues. Pregnenolone is the precursor to GONADAL STEROID HORMONES and the adrenal CORTICOSTEROIDS.Pregnenolone Carbonitrile: A catatoxic steroid and microsomal enzyme inducer having significant effects on the induction of cytochrome P450. It has also demonstrated the potential for protective capability against acetaminophen-induced liver damage.17-alpha-Hydroxypregnenolone: A 21-carbon steroid that is converted from PREGNENOLONE by STEROID 17-ALPHA-HYDROXYLASE. It is an intermediate in the delta-5 pathway of biosynthesis of GONADAL STEROID HORMONES and the adrenal CORTICOSTEROIDS.Cholesterol Side-Chain Cleavage Enzyme: A mitochondrial cytochrome P450 enzyme that catalyzes the side-chain cleavage of C27 cholesterol to C21 pregnenolone in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP11A1 gene, catalyzes the breakage between C20 and C22 which is the initial and rate-limiting step in the biosynthesis of various gonadal and adrenal steroid hormones.Dehydroepiandrosterone: A major C19 steroid produced by the ADRENAL CORTEX. It is also produced in small quantities in the TESTIS and the OVARY. Dehydroepiandrosterone (DHEA) can be converted to TESTOSTERONE; ANDROSTENEDIONE; ESTRADIOL; and ESTRONE. Most of DHEA is sulfated (DEHYDROEPIANDROSTERONE SULFATE) before secretion.Pregnanolone: A pregnane found in the urine of pregnant women and sows. It has anesthetic, hypnotic, and sedative properties.Pregnanes: Saturated derivatives of the steroid pregnane. The 5-beta series includes PROGESTERONE and related hormones; the 5-alpha series includes forms generally excreted in the urine.Pregnenes: Unsaturated derivatives of PREGNANES.Steroids: A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)Progesterone Reductase: An enzyme that catalyzes the reduction of a 3 beta-hydroxy-delta(5)-steroid to 3-oxo-delta(4)-steroid in the presence of NAD. It converts pregnenolone to progesterone and dehydroepiandrosterone to androstenedione. EC 1.1.1.145.3-Hydroxysteroid Dehydrogenases: Catalyze the oxidation of 3-hydroxysteroids to 3-ketosteroids.Progesterone: The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS.Hydroxysteroids: Steroids in which one or more hydroxy groups have been substituted for hydrogen atoms either within the ring skeleton or on any of the side chains.Adrenal Cortex: The outer layer of the adrenal gland. It is derived from MESODERM and comprised of three zones (outer ZONA GLOMERULOSA, middle ZONA FASCICULATA, and inner ZONA RETICULARIS) with each producing various steroids preferentially, such as ALDOSTERONE; HYDROCORTISONE; DEHYDROEPIANDROSTERONE; and ANDROSTENEDIONE. Adrenal cortex function is regulated by pituitary ADRENOCORTICOTROPIN.Steroid 17-alpha-Hydroxylase: A microsomal cytochrome P450 enzyme that catalyzes the 17-alpha-hydroxylation of progesterone or pregnenolone and subsequent cleavage of the residual two carbons at C17 in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP17 gene, generates precursors for glucocorticoid, androgen, and estrogen synthesis. Defects in CYP17 gene cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL) and abnormal sexual differentiation.Adrenodoxin: An iron-sulfur protein which serves as an electron carrier in enzymatic steroid hydroxylation reactions in adrenal cortex mitochondria. The electron transport system which catalyzes this reaction consists of adrenodoxin reductase, NADP, adrenodoxin, and cytochrome P-450.5-alpha-Dihydroprogesterone: A biologically active 5-alpha-reduced metabolite of plasma PROGESTERONE. It is the immediate precursor of 5-alpha-pregnan-3-alpha-ol-20-one (ALLOPREGNANOLONE), a neuroactive steroid that binds with GABA(A) RECEPTOR.Adrenal Glands: A pair of glands located at the cranial pole of each of the two KIDNEYS. Each adrenal gland is composed of two distinct endocrine tissues with separate embryonic origins, the ADRENAL CORTEX producing STEROIDS and the ADRENAL MEDULLA producing NEUROTRANSMITTERS.Hydroxyprogesterones: Metabolites or derivatives of PROGESTERONE with hydroxyl group substitution at various sites.Hydroxycholesterols: Cholesterol which is substituted by a hydroxy group in any position.20-alpha-Dihydroprogesterone: A biologically active 20-alpha-reduced metabolite of PROGESTERONE. It is converted from progesterone to 20-alpha-hydroxypregn-4-en-3-one by the 20-ALPHA-HYDROXYSTEROID DEHYDROGENASE in the CORPUS LUTEUM and the PLACENTA.Dehydroepiandrosterone Sulfate: The circulating form of a major C19 steroid produced primarily by the ADRENAL CORTEX. DHEA sulfate serves as a precursor for TESTOSTERONE; ANDROSTENEDIONE; ESTRADIOL; and ESTRONE.Androstenedione: A delta-4 C19 steroid that is produced not only in the TESTIS, but also in the OVARY and the ADRENAL CORTEX. Depending on the tissue type, androstenedione can serve as a precursor to TESTOSTERONE as well as ESTRONE and ESTRADIOL.Diazepam Binding Inhibitor: An 86-amino acid polypeptide, found in central and peripheral tissues, that displaces diazepam from the benzodiazepine recognition site on the gamma-aminobutyric acid receptor (RECEPTORS, GABA). It also binds medium- and long-chain acyl-CoA esters and serves as an acyl-CoA transporter. This peptide regulates lipid metabolism.Aminoglutethimide: An aromatase inhibitor that is used in the treatment of advanced BREAST CANCER.17-alpha-Hydroxyprogesterone: A metabolite of PROGESTERONE with a hydroxyl group at the 17-alpha position. It serves as an intermediate in the biosynthesis of HYDROCORTISONE and GONADAL STEROID HORMONES.Cytochrome P-450 Enzyme System: A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.Pregnanediones: Pregnane derivatives in which two side-chain methyl groups or two methylene groups in the ring skeleton (or a combination thereof) have been oxidized to keto groups.Cyanoketone: 2 alpha-Cyano-17 beta-hydroxy-4,4',17 alpha-trimethylandrost-5-ene-3-one. An androstenolone-nitrile compound with steroidogenesis-blocking activity.Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Androsterone: A metabolite of TESTOSTERONE or ANDROSTENEDIONE with a 3-alpha-hydroxyl group and without the double bond. The 3-beta hydroxyl isomer is epiandrosterone.Anesthesiology: A specialty concerned with the study of anesthetics and anesthesia.Steroid Isomerases: Enzymes that catalyze the transposition of double bond(s) in a steroid molecule. EC 5.3.3.Receptors, sigma: A class of cell surface receptors recognized by its pharmacological profile. Sigma receptors were originally considered to be opioid receptors because they bind certain synthetic opioids. However they also interact with a variety of other psychoactive drugs, and their endogenous ligand is not known (although they can react to certain endogenous steroids). Sigma receptors are found in the immune, endocrine, and nervous systems, and in some peripheral tissues.Testosterone: A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.Corpus Luteum: The yellow body derived from the ruptured OVARIAN FOLLICLE after OVULATION. The process of corpus luteum formation, LUTEINIZATION, is regulated by LUTEINIZING HORMONE.Androstanes: The family of steroids from which the androgens are derived.Hexobarbital: A barbiturate that is effective as a hypnotic and sedative.Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)TRPM Cation Channels: A subgroup of TRP cation channels named after melastatin protein. They have the TRP domain but lack ANKYRIN repeats. Enzyme domains in the C-terminus leads to them being called chanzymes.Granulosa Cells: Supporting cells for the developing female gamete in the OVARY. They are derived from the coelomic epithelial cells of the gonadal ridge. Granulosa cells form a single layer around the OOCYTE in the primordial ovarian follicle and advance to form a multilayered cumulus oophorus surrounding the OVUM in the Graafian follicle. The major functions of granulosa cells include the production of steroids and LH receptors (RECEPTORS, LH).Gas Chromatography-Mass Spectrometry: A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.Adrenocorticotropic Hormone: An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP).Progestins: Compounds that interact with PROGESTERONE RECEPTORS in target tissues to bring about the effects similar to those of PROGESTERONE. Primary actions of progestins, including natural and synthetic steroids, are on the UTERUS and the MAMMARY GLAND in preparation for and in maintenance of PREGNANCY.Receptors, GABA-A: Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Neurites: In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell.Allosteric Regulation: The modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES.Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.Nonprescription Drugs: Medicines that can be sold legally without a DRUG PRESCRIPTION.Prostatic Hyperplasia: Increase in constituent cells in the PROSTATE, leading to enlargement of the organ (hypertrophy) and adverse impact on the lower urinary tract function. This can be caused by increased rate of cell proliferation, reduced rate of cell death, or both.Tablets: Solid dosage forms, of varying weight, size, and shape, which may be molded or compressed, and which contain a medicinal substance in pure or diluted form. (Dorland, 28th ed)Hair: A filament-like structure consisting of a shaft which projects to the surface of the SKIN from a root which is softer than the shaft and lodges in the cavity of a HAIR FOLLICLE. It is found on most surfaces of the body.Prostate: A gland in males that surrounds the neck of the URINARY BLADDER and the URETHRA. It secretes a substance that liquefies coagulated semen. It is situated in the pelvic cavity behind the lower part of the PUBIC SYMPHYSIS, above the deep layer of the triangular ligament, and rests upon the RECTUM.Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness.
Luteinizing hormone inhibits conversion of pregnenolone to progesterone in luteal cells from rats on day 19 of pregnancy. (1/488)
We have previously reported that intrabursal ovarian administration of LH at the end of pregnancy in rats induces a decrease in luteal progesterone (P4) synthesis and an increase in P4 metabolism. However, whether this local luteolytic effect of LH is exerted directly on luteal cells or on other structures, such as follicular or stromal cells, to modify luteal function is unknown. The aim of the present study was to determine the effect of LH on isolated luteal cells obtained on Day 19 of pregnancy. Incubation of luteal cells with 1, 10, 100, or 1000 ng/ml of ovine LH (oLH) for 6 h did not modify basal P4 production. The addition to the culture medium of 22(R)-hydroxycholesterol (22R-HC, 10 microgram/ml), a membrane-permeable P4 precursor, or pregnenolone (10(-2) microM) induced a significant increase in P4 accumulation in the medium in relation to the control value. When luteal cells were preincubated for 2 h with oLH, a significant (p < 0.01) reduction in the 22R-HC- or pregnenolone-stimulated P4 accumulation was observed. Incubation of luteal cells with dibutyryl cAMP (1 mM, a cAMP analogue) plus isobutylmethylxanthine (1 mM, a phosphodiesterase inhibitor) also inhibited pregnenolone-stimulated P4 accumulation. Incubation with an inositol triphosphate synthesis inhibitor, neomycin (1 mM), or an inhibitor of intracellular Ca2+ mobilization, (8,9-N, N-diethylamino)octyl-3,4,5-trimethoxybenzoate (1 mM), did not prevent the decrease in pregnenolone-stimulated P4 secretion induced by oLH. It was concluded that the luteolytic action of LH in late pregnancy is due, at least in part, to a direct action on the luteal cells and that an increase in intracellular cAMP level might mediate this effect. (+info)Lack of zonal uptake of estrone sulfate in enriched periportal and perivenous isolated rat hepatocytes. (2/488)
The zonal uptake of estrone sulfate (E1S; 1 to 400 microM) was investigated in periportal and perivenous rat hepatocytes and cells isolated from whole liver (regular hepatocytes). Transport of E1S by periportal, perivenous, and regular hepatocytes was described by saturable (Kms of 24 to 26 microM and Vmaxs of 1.8 nmol/min/mg protein) and nonsaturable components (2.5 to 3.2 microl/min/mg protein) that were not different among the zonal regions (p >.05, ANOVA). These kinetic constants represented pooled values for the entire complement of transporters for E1S, including two known transporters of E1S: Ntcp, Na+-taurocholate cotransporting polypeptide, and oatp1, the organic anion transporting polypeptide cloned from rat liver. Uptake of E1S was significantly reduced by estradiol 17beta-glucuronide (50 microM) and bumetanide (200 microM), and was inhibited strongly and competitively by pregnenolone sulfate with an inhibition constant of 6.7 microM. Further segregation of the kinetic constants as the sodium-dependent and -independent systems was achieved through simultaneous fitting of data obtained in the presence and absence of sodium from parallel hepatocytic uptake studies. For the periportal, perivenous, and regular hepatocytes, two saturable systems: a sodium-dependent transport system, characterized by similar Vmaxs (1.1 to 1.4 nmol/min/mg protein) and Kms (49 to 55 microM), a sodium-independent transport system of comparable Vmaxs (0.70 to 0.84 nmol/min/mg protein) and Kms (16 to 22 microM), and a linear clearance of 1.7 to 2.7 microl/min/mg protein (ANOVA, p >.05) were obtained. The data suggest that hepatic uptake of E1S involved sodium-dependent and -independent transporter systems. No heterogeneity in transport was observed. (+info)Short-time effects of neuroactive steroids on rat cortical Ca2+-ATPase activity. (3/488)
Recent experimental evidence indicates that some steroid hormones, apart from their well-documented genomic actions, could produce non-genomic rapid effects, and are potent modulators of the plasma membrane proteins, including voltage- and ligand-operated ion channels or G protein-coupled receptors. Neuroactive steroids, 17beta-estradiol, testosterone, pregnenolone sulfate and dehydroepiandrosterone sulfate, after a short-time incubation directly modulated the activity of plasma membrane Ca2+-ATPase purified from synaptosomal membranes of rat cortex. The sulfate derivatives of dehydroepiandrosterone and pregnenolone applied at concentrations of 10-11-10-6 M, showed an inverted U-shape potency in the regulation of Ca2+-ATPase activity. At physiologically relevant concentrations (10-8-10-9 M) a maximal enhancement of the basal activity reached 200%. Testosterone (10-11-10-6 M) and 17beta-estradiol (10-12-10-9 M) caused a dose-dependent increase in the hydrolytic ability of Ca2+-ATPase, and the activity with the highest concentration of steroids reached 470% and 200%, respectively. All examined steroids decreased the stimulatory effect of a naturally existing activator of the calcium pump, calmodulin. The present study strongly suggests that the plasma membrane calcium pump could be one of the possible membrane targets for a non-genomic neuroactive steroid action. (+info)Effect of DL111-IT on progesterone biosynthesis and viability of rat luteal cells in vitro. (4/488)
AIM: To study the influence of DL111-IT on progesterone biosynthesis of cultured luteal cells (LC). METHODS: LC viability was assessed with trypan blue dye exclusion and progesterone concentration was measured with radioimmunoassay. RESULTS: DL111-IT decreased the viability of LC after 24-h incubation, its ED50 being 7.7 (95% confidence limits: 7.1-8.5) mg.L-1. DL111-IT inhibited basal secretion of progesterone in a concentration-dependent manner, and 3 mg.L-1 decreased progesterone concentration by 25% vs control. DL111-IT 3 mg.L-1 also inhibited the stimulatory effect of forskolin (cAMP activator) 10 mumol.L-1 and pregnenolone [converted to progesterone by 3 beta-hydroxysteroid dehydrogenase-isomerase complex (3 beta-HSD)] 10 mumol.L-1 on progesterone production in cultured LC, and their inhibitory rates were 43% and 155%, respectively. At the same concentration, DL111-IT did not influence hCG-induced progesterone production. CONCLUSION: DL111-IT inhibited progesterone synthesis by suppressing the conversion of pregnenolone to progesterone (inactivating 3 beta-HSD) and suppressed the activity of cAMP. DL111-IT 6-24 mg.L-1 decreased the viability of LC. (+info)Pregnenolone esterification in Saccharomyces cerevisiae. A potential detoxification mechanism. (5/488)
While studying the effect of steroids on the growth of the yeast Saccharomyces cerevisiae, we found that pregnenolone was converted into the acetate ester. This reaction was identified as a transfer of the acetyl group from acetyl-CoA to the 3beta-hydroxyl group of pregnenolone. The corresponding enzyme, acetyl-CoA:pregnenolone acetyltransferase (APAT) is specific for Delta5- or Delta4-3beta-hydroxysteroids and short-chain acyl-CoAs. The apparent Km for pregnenolone is approximately 0.5 microm. The protein associated with APAT activity was partially purified and finally isolated from an SDS/polyacrylamide gel. Tryptic peptides were generated and N-terminally sequenced. Two peptide sequences allowed the identification of an open reading frame (YGR177c, in the S. cerevisiae genome database) translating into a 62-kDa protein of hitherto unknown function. This protein encoded by a gene known as ATF2 displays 37% identity with an alcohol acetyltransferase encoded by the yeast gene ATF1. Disruption of ATF2 led to the complete elimination of APAT activity and consequently abolished the esterification of pregnenolone. In addition, a toxic effect of pregnenolone linked to the disruption of ATF2 was observed. Pregnenolone toxicity is more pronounced when the atf2-Delta mutation is introduced in a yeast strain devoid of the ATP-binding cassette transporters, PDR5 and SNQ2. Our results suggest that Atf2p (APAT) plays an active role in the detoxification of 3beta-hydroxysteroids in association with the efflux pumps Pdr5p and Snq2p. (+info)The concentration of adrenodoxin reductase limits cytochrome p450scc activity in the human placenta. (6/488)
We have previously reported that cytochrome P450scc activity in the human placenta is limited by the supply of electrons to the P450scc [Tuckey, R. C., Woods, S. T. & Tajbakhsh, M. (1997) Eur. J. Biochem. 244, 835-839]. The aim of the present study was to determine whether it is adrenodoxin reductase, adrenodoxin or both which limits cytochrome P450scc activity and hence progesterone synthesis in the placenta. We found that the concentrations of adrenodoxin reductase and adrenodoxin in placental mitochondria were both considerably lower than the concentrations of these proteins in the bovine adrenal cortex. When P450scc activity assays were carried out at high mitochondrial protein concentrations, we found that the addition of exogenous adrenodoxin reductase to sonicated mitochondria rescued pregnenolone synthesis to a level above that for intact mitochondria, showing that adrenodoxin is near-saturating in vivo. In contrast, pregnenolone synthesis by sonicated mitochondria was almost zero even after the addition of human adrenodoxin. This shows that the concentration of endogenous adrenodoxin reductase was insufficient to support appreciable rates of pregnenolone synthesis, even when concentrated mitochondrial samples were used. Comparative studies with human and bovine adrenodoxin reductase have revealed that a twofold higher concentration of human adrenodoxin reductase is required for maximal P450scc activity in the presence of saturating human adrenodoxin. Thus, not only is the adrenodoxin concentration low in placental mitochondria, but the amount required for maximal P450scc activity is higher than that for the bovine reductase. Overall, the data indicate that the adrenodoxin reductase concentration limits the activity of P450scc in placental mitochondria and hence determines the rate of progesterone synthesis. (+info)Identification by chimera formation and site-selected mutagenesis of a key amino acid residue involved in determining stereospecificity of guinea pig 3-hydroxysteroid sulfotransferase isoforms. (7/488)
The 3-hydroxysteroid sulfotransferases that have been isolated and cloned from humans and rodents appear to have broad substrate specificities. In the guinea pig, however, two 3-hydroxysteroid sulfotransferases have been isolated that function according to an innate stereospecificity: the alpha-isoform acts on steroids with a 3-hydroxyl group oriented in the alpha position, whereas the beta-isoform acts on steroids where the 3-hydroxyl group is in a beta orientation. To examine the structural basis for this remarkable stereoselectivity, chimeras of the two enzymes, which are 87% identical, were constructed. A chimera consisting of the NH(2)-terminal 91 amino acids of the alpha-isoform and the COOH-terminal 196 amino acids of the beta-isoform displayed activity similar to that of the alpha-isoform. Site-selected mutagenesis of this 3alpha/beta-hydroxysteroid sulfotransferase chimera involving the 12 amino acid differences that exist between the two isoforms within the 91 amino acid NH(2)-terminal region revealed that the amino acid residue at position 51 plays a fundamental role in determining the stereospecificity exhibited by the alpha- and beta-isoforms, i.e. if residue 51 is an asparagine, alpha activity predominates, whereas if an isoleucine is in that position, beta activity prevails. (+info)Response-rate suppression in operant paradigm as predictor of soporific potency in rats and identification of three novel sedative-hypnotic neuroactive steroids. (8/488)
Novel neuroactive steroids were evaluated for their effects on operant responding, rotorod motor performance, and electroencephalogram recording in rats. Co 134444, Co 177843, and Co 127501 were compared with the prototypical gamma-aminobutyric acid(A)-positive allosteric modulators triazolam, zolpidem, pentobarbital, pregnanolone, and CCD 3693. Each of the compounds produced a dose-related decrease in response rates under a variable-interval 2-min schedule of positive reinforcement in an operant paradigm. In addition, all compounds produced a dose-related increase in ataxia and significant increases in nonrapid eye movement sleep in this experiment or have been previously reported to do so. Co 134444, Co 177843, and Co 127501 increased nonrapid eye movement sleep at doses that had no effect on rapid eye movement sleep. All of the compounds were more potent at decreasing operant responding than they were at increasing ataxia. Furthermore, the potency of compounds to produce response-rate suppression in an operant paradigm appeared to be a better predictor of soporific potency than did potency in the rotorod assay. The screening for sedative-hypnotic activity resulted in the identification of the novel orally active neuroactive steroids Co 134444, Co 177843, and Co 127501. (+info)
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Fred Meyer - Only Natural Pregnenolone, 15 mg - 60 Capsules
DHEA and Pregnenolone Safe for Prostate?
SFARI | Randomized controlled pilot trial of pregnenolone in autism
Pregnenolone sulfate enhances survival of adult-generated hippocampal granule cells via sustained presynaptic potentiation. -...
Douglas Labs Pregnenolone - 100 Tablets - eVitamins.com
Pregnenolone (50 mg)
Life Extension Pregnenolone 100 mg - 100 Capsules - eVitamins Canada
Cognitex® with Pregnenolone & Brain Shield™ - 90 Softgels
Life Extension Pregnenolone 50 mg 100 Capsules, Life Extension, 00302
PrecursorProgesteroneDHEASulfateCholesterolCapsulesTestosteroneHormonesBody'sSteroid hormoneAdrenalSupplemental pregnenoloneSupplementCapsuleMitochondriaWild yamEstrogenMoodNaturallyDeclineSupplementationNegative allosteric modulatorLevelsDoseLiverGABAMetabolitesHydroxylationSteroidogenesisReceptorMemoryMicronized and sustained released
Precursor10
- Pregnenolone ( P5 ), or pregn-5-en-3β-ol-20-one , is an endogenous steroid and precursor / metabolic intermediate in the biosynthesis of most of the steroid hormones , including the progestogens , androgens , estrogens , glucocorticoids , and mineralocorticoids . (wikipedia.org)
- According to the Langone Medical Center at New York University, supplementing with extra pregnenolone may not cause the body to produce more of the hormones to which pregnenolone is the precursor. (livestrong.com)
- Pregnenolone Plus, by Neurobiologix, is a custom formula that provides pregnenolone and the active precursor niacinamide for ultimate delivery of pregnenolone and aid in the protection of the mitochondria. (prohealth.com)
- Pregnenolone is the key precursor pro-hormone involved in maintaining sufficient steroid hormone levels in the body. (prohealth.com)
- Pregnenolone is the first steroid to be derived from cholesterol in the pathway of steroidogenesis, and it is the common precursor for all of the adrenal and gonadal steroids. (biovendor.com)
- Pregnenolone is not a steroid but a steroid hormone precursor manufactured in the body from cholesterol. (vitaminlife.com)
- Pregnenolone - Pregnenalone is the sometimes referred to the r hormone' as it serves as the precursor to steroid hormones. (pureprescriptions.com)
- Pregnenolone, 3-alpha-hydroxy-5-beta-pregnen-20-one, is a precursor to over 150 steroid hormones and is produced naturally in the body from cholesterol. (pureprescriptions.com)
- Description Pregnenolone serves as the common precursor in the formation of the adrenocorticoids and other steroid hormones. (chemicalbook.com)
- When the body is under chronic stress, pregnenolone, the precursor to all other steroidal hormones, is diverted to produce cortisol (known as pregnenolone steal or cortisol escape). (mylabsforlife.com)
Progesterone7
- Pregnenolone and its 3β- sulfate , pregnenolone sulfate, like DHEA, DHEA sulfate , and progesterone, belong to the group of neurosteroids that are found in high concentrations in certain areas of the brain, and are synthesized there. (wikipedia.org)
- However, progesterone did and with similar affinity to pregnenolone, although unlike pregnenolone, it did not increase binding of MAP2 to tubulin . (wikipedia.org)
- Pregnenolone certainly plays a vital part in hormone production: From the steroid hormone Progesterone , to estrogen , testosterone and the dhea steroid hormone (short for dehydroepiandrosterone), Pregnenolone is behind them all. (antiaging-systems.com)
- This antibody is specific for 17a-OH-Pregnenolone, but will also recognize 17a-OH-Progesterone. (acris-antibodies.com)
- Pregnenolone is converted in the liver to DHEA (dehydroepiandrosterone) and Progesterone (and ultimately other hormones such as estrogen and testosterone). (vitaminlife.com)
- Produced from cholesterol, pregnenolone has been described as the "grandmother of all steroid hormones," since all 150 steroid hormones in the body - including testosterone, estrogen, progesterone, cortisol, and aldosterone - are derived from pregnenolone. (drjamiephd.com)
- The body will typically convert pregnenolone into DHEA or progesterone according to its needs. (drjamiephd.com)
DHEA18
- Using pregnenolone may elevate your DHEA levels, and DHEA can increase estrogen and testosterone levels. (iherb.com)
- DHEA and pregnenolone supplements may restore natural levels. (livestrong.com)
- The hormone pregnenolone causes the body to produce many other hormones, such as testosterone, estrogen, cortisone and DHEA. (livestrong.com)
- Talk to your doctor before taking pregnenolone or DHEA. (livestrong.com)
- Take DHEA separately from pregnenolone until you know how each hormone affects you. (livestrong.com)
- Take a reduced dose of DHEA while taking pregnenolone, after you've determined your body's reaction to each substance. (livestrong.com)
- Reduce your DHEA dose by an amount equal to your dose of pregnenolone. (livestrong.com)
- Seek emergency medical care if you have an allergic reaction to DHEA or pregnenolone, with symptoms such as itching, swollen throat or difficulty breathing. (livestrong.com)
- Read the label of any DHEA or pregnenolone supplement you consider taking. (livestrong.com)
- According to physician and medical writer Dr. Ray Sahelian, many supplement makers use an ingredient called diosgenin that converts to pregnenolone and DHEA in lab tests but not in the human body. (livestrong.com)
- Ensure that your supplement lists "DHEA" or "pregnenolone" as the only ingredient. (livestrong.com)
- Stop supplementing with pregnenolone or DHEA for a short time to allow your hormone levels to return to their natural levels. (livestrong.com)
- Avoid DHEA, pregnenolone and other steroid supplements if you are under 40 years of age and you have normal levels of these hormones. (livestrong.com)
- A 1995 clinical study produced pregnenolone testimonials vouching for its effectiveness, particularly in relation to use of dhea to improve memory capabilities. (antiaging-systems.com)
- During this trial, pregnenolone was found to be a potent memory enhancer - and possibly up to 100 times more effective than dhea. (antiaging-systems.com)
- I no sooner ordered this product when I read about the potential hazards of taking 50 mg pregnenolone -- especially if you are also taking DHEA supplements. (iherb.com)
- Likewise with the DHEA: if you are taking DHEA while you are also taking pregnenolone, it is wise to take only half a dose of each and to limit the pregnenolone to 5 days on with periodic 'hormone vacations. (iherb.com)
- As pregnenolone is diverted to cortisol, DHEA depletion begins. (mylabsforlife.com)
Sulfate5
- Pregnenolone and its sulfate ester may improve cognitive and memory function. (wikipedia.org)
- In contrast to pregnenolone, pregnenolone sulfate did not bind to microtubules . (wikipedia.org)
- Although pregnenolone itself does not possess these activities, its metabolite pregnenolone sulfate is a negative allosteric modulator of the GABA A receptor as well as a positive allosteric modulator of the NMDA receptor . (wikipedia.org)
- In addition, pregnenolone sulfate has been shown to activate the transient receptor potential M3 (TRPM3) ion channel in hepatocytes and pancreatic islets causing calcium entry and subsequent insulin release. (wikipedia.org)
- The determination of pregnenolone in serum may be useful for studying its metabolite, pregnenolone sulfate, which has been reported to have various effects in the mammalian brain and central nervous system. (biovendor.com)
Cholesterol3
- Pregnenolone is synthesized from cholesterol . (wikipedia.org)
- [ citation needed ] There are two intermediates in the transformation of cholesterol into pregnenolone, 22 R -hydroxycholesterol and 20α,22 R -dihydroxycholesterol , and all three steps in the transformation are catalyzed by P450scc. (wikipedia.org)
- Hi, If total cholesterol increases steadily over several years, and pregnenolone remains bottom of the barrel-low (along with other sex-hormones) what would be the location of the metabolic defect? (apoe4.info)
Capsules1
- As a result, I emptied out each of the 50 mg capsules and split the pregnenolone powder into 5 x 10 mg dosages. (iherb.com)
Testosterone2
- Like its counterparts estrogen, testosterone, cortisone and Progresterone, dehydroepiandrosterone is a steroid hormone that Pregnenolone helps to produce. (antiaging-systems.com)
- Oxidative cleavage of the two-carbon side chain of pregnenolone and subsequent enzymatic oxidations and isomerization lead to C19 steroids, including the androgens testosterone and dihydrotestosterone. (chemicalbook.com)
Hormones4
- Pregnenolone is the starting point from which all steroid hormones are manufactured in our bodies. (iherb.com)
- Often described as the mother of all hormones, naturally occurring pregnenolone acts to improve memory and combat depression - and has powerful anti-inflammatory arthritis pain relieving properties. (antiaging-systems.com)
- This explains why it's inadvertently called the mother of all hormones, the pregnenolone hormone and sometimes the adrenal hormone (being formed in the adrenal gland and central nervous system). (antiaging-systems.com)
- I didn't have baselines of my other hormones before and after supplementing pregnenolone, but my pregnenolone responded well to cheap 10 mg/day upon repeated repeat testing. (apoe4.info)
Body's2
- Pregnenolone acts as a key building block in the body's steroid hormone production during the cellular growth process powered by mitochondria. (antiaging-systems.com)
- It is important to note that as we age the body's natural pregnenolone levels decrease. (vitaminlife.com)
Steroid hormone3
- Pregnenolone isn't actually a steroid hormone, but what's known as a metabolite - the molecules forming part of the chemical chain behind human development. (antiaging-systems.com)
- Without pregnenolone there can be no human steroid hormone production. (neurobiologix.com)
- Pregnenolone is a natural steroid hormone in the body that's been shown to boost the immune system, mood, and memory. (drjamiephd.com)
Adrenal4
- Pregnenolone is a substance produced within the body, including in the adrenal glands and liver. (vitaminworld.com)
- Pregnenolone is a natural pro-hormone produced primarily in the adrenal glands, but in smaller amounts by many other organs and tissues of the human body, including liver, brain, skin, gonads, and even the retina of the eye. (prohealth.com)
- Elevated pregnenolone levels occur in forms of congenital adrenal hyperplasia. (biovendor.com)
- Pregnenolone is often used in HPA-resetting / adrenal fatigue programs and anti-aging protocols to increase energy and stamina, strengthen the immune system, and support brain function. (drjamiephd.com)
Supplemental pregnenolone1
- Therefore, supplemental pregnenolone may play an important role in todays aging population supporting lean body mass, strength, immune health as well as bone and cardiovascular health. (vitaminlife.com)
Supplement7
- For its use as a medication or supplement, see Pregnenolone (medication) . (wikipedia.org)
- for information on pregnenolone as a medication or supplement, see the pregnenolone (medication) article. (wikipedia.org)
- While pregnenolone benefits had been established and found safe to use as a pregnenolone supplement, it wasn't until the 1990's that pregnenolone rose to prominence again - this time as an antiaging memory enhancer and an aid to boost memory. (antiaging-systems.com)
- The scientific community was interested in how the pregenolone metabolic process could influence mental health, stress and depression, with pregnenolone supplementation perhaps acting as an anti depression supplement. (antiaging-systems.com)
- Why consider a Pregnenolone hormone supplement? (antiaging-systems.com)
- By the age of 70 Pregnenolone levels in the body may have declined by up to 60 per cent - which is why older people may consider taking a pregnenolone dosage as part of a regular pregnenolone supplement. (antiaging-systems.com)
- Pregnenolone is a potent memory enhancing supplement. (doublewoodsupplements.com)
Capsule2
- 50mg of Pregnenolone is delivered in each capsule serving. (vitaminworld.com)
- Pregnenolone Plus consists of 40mg of natural pregnenolone and 75 mg of niacinamide per capsule. (neurobiologix.com)
Mitochondria1
- In a typical human cell there may be thousands of mitochondria, which also contain pregnenolone. (antiaging-systems.com)
Wild yam2
- The compound diosgenin is extracted from wild yam and undergoes a proprietary synthetic process to develop the pregnenolone compound. (pureprescriptions.com)
- The human body cannot metabolize wild yam into pregnenolone. (pureprescriptions.com)
Estrogen1
- Women embarking on the post-menopausal stage of their life may also find pregnenolone benefits them, as it offers a natural estrogen therapy and way to increase estrogen. (antiaging-systems.com)
Mood3
- Stop taking pregnenolone and call your doctor if you develop a hormonal imbalance with side effects such as insomnia, acne, anxiety, bad mood and irregular heart beat. (livestrong.com)
- Mood Support: Pregnenolone has been reported to help promote feelings of emotional well-being. (pureprescriptions.com)
- One study suggested that pregnenolone supported positive mood and feelings of motivation by mediating dopamine release. (pureprescriptions.com)
Naturally1
- Pregnenolone levels can naturally decline with age. (vitaminworld.com)
Decline1
- In addition to stress and depression, pregnenolone supplementation also entered the antiaging arena to address mental decline and memory loss, and act as a memory enhancer. (antiaging-systems.com)
Supplementation2
- Practitioners are advised to test pregnenolone levels before making the decision to commence supplementation, and to monitor levels if supplementation is initiated, ensuring that proper levels are maintained. (pureprescriptions.com)
- Due to its effects on the GABA receptor in the central nervous system, supplementation with pregnenolone could cause problems in people with a history of seizures. (pureprescriptions.com)
Negative allosteric modulator1
- Pregnenolone is an allosteric endocannabinoid , as it is a negative allosteric modulator of the CB 1 receptor . (wikipedia.org)
Levels4
- As optimal levels of pregnenolone are known to be important for mental health and cognitive functions, pregnenolone therapy came to be viewed as an important anti aging product, along with fellow cognitive enhancers such as Idebenone , piracetam , Hydergine and Vitamin B12 . (antiaging-systems.com)
- Men and women typically have differing amounts of pregnenolone, while lifestyle, exercise, stress levels and age also play a part. (antiaging-systems.com)
- This product should not be taken by individuals with healthy levels of pregnenolone. (pureprescriptions.com)
- My thoughts, knowing nothing about this other than I also had bottom of the barrel pregnenolone (two in a row to verify), are to bring up the pregnenolone and then compare hormone levels as a really basic start. (apoe4.info)
Dose1
- When it comes time to reorder this product, I will NOT order this large a dose of pregnenolone. (iherb.com)
Liver1
- Itis formulated in a lipid matrix to bypass the liver so that the pregnenolone is presented directly to the systemic circulation, and it is micronized to a particle size of less than 50 microns for optimal absorption. (pdlabsrx.com)
GABA3
- Pregnenolone is known to modulate at least two key nerve receptors systems in the brain: NMDA receptors and GABA receptors. (prohealth.com)
- Memory Support: Animal studies have reported that pregnenolone may help to enhance memory by modulating N-methyl-D-aspartate (NMDA) and gamma aminobutyrate (GABA) receptor activity in the brain. (pureprescriptions.com)
- Pregnenolone may inhibit drugs used to increase GABA activity (e.g. (pureprescriptions.com)
Metabolites1
- Immune Health: One study indicated that the 7-hydroxy metabolites from pregnenolone may help promote healthy immune system response. (pureprescriptions.com)
Hydroxylation1
- 17a-OH-Pregnenolone is an intermediate in steroid biosynthesis and is produced through hydroxylation of pregnenolone by the enzyme 17-alpha-hydroxylase. (acris-antibodies.com)
Steroidogenesis1
- Steroidogenesis , showing pregnenolone near top left. (wikipedia.org)
Receptor2
- Pregnenolone is involved in a natural negative feedback loop against CB 1 receptor activation in animals. (wikipedia.org)
- Pregnenolone has been found to act as an agonist of the pregnane X receptor . (wikipedia.org)
Memory2
- As a memory enhancer, the pregnenolone hormone action appears to aid knowledge acquisition and boost long term memory capabilities. (antiaging-systems.com)
- One study suggested that pregnenolone helped promote post-training task learning and memory. (pureprescriptions.com)
Micronized and sustained released2
- Pregnenolone 150mg is micronized and sustained released in a lipid matrix. (picknsave.com)
- Pregnenolone 50 mg (plant source) is micronized and sustained released. (pdlabsrx.com)
