Showing papers on "Pregnenolone published in 1967"
TL;DR: Observations indicate that amino-glutethimide inhibits the conversion of cholesterol to pregnenolone, and results in adrenal enlargement, an effect that appears to be partly due to cholesterol accumulation and partly to the adrenal growth-promoting effect of increased endogenous ACTH.
Abstract: Amino-glutethimide inhibits corticosterone synthesis by the rat adrenal cortex both in vivo and in vitro. In intact rats the decrease in corticosterone production is accompanied by an increase in plasma ACTH. In the presence of endogenous or exogenous ACTH, amino-glutethimide causes marked accumulation of adrenal cholesterol. These observations, plus the fact that amino-glutethimide does not impair the conversion of pregnenolone to corticosterone, indicate that the drug inhibits the conversion of cholesterol to pregnenolone. Aminoglutethimide administration results in adrenal enlargement, an effect that appears to be partly due to cholesterol accumulation and partly due to the adrenal growth-promoting effect of increased endogenous ACTH.
265 citations
TL;DR: Results suggest the involvement of a haem-containing protein, ‘P-450’ as the oxygen-binding site in the cholesterol side-chain cleavage system of bovine adrenal cortex.
Abstract: 1
The cholesterol side-chain cleavage system of bovine adrenal cortex has been studied using extracts of sonicated mitochondria as source of enzymic activity.
2
The system has been found to be inhibited by carbon monoxide, this inhibition being consistent with competition between carbon monoxide and oxygen for an enzymic site.
3
The inhibition by carbon monoxide is reversed by light, the most effective wavelength being 450 mμ. These results suggest the involvement of a haem-containing protein, ‘P-450’ as the oxygen-binding site in the cholesterol side-chain cleavage system.
4
Attempts have been made to isolate intermediates between cholesterol and pregnenolone. Neither 20α-hydroxycholesterol nor 20α,22-dihydroxycholesterol have been found.
203 citations
80 citations
TL;DR: Individual follicles, with their enclosed oocytes, were dissected from the ovary of the leopard frog, Rana pipiens, and their response to steroid hormones studied, and steroids appear to act directly on the oocyte and calcium ions appear to be important for the biological action of the steroids.
Abstract: SummaryIndividual follicles, with their enclosed oocytes, were dissected from the ovary of the leopard frog, Rana pipiens, and their response to steroid hormones studied. Biologically and chemically related substance, progesterone, pregnenolone and 11-deoxycorticosterone, were most effective in producing germinal vesicle breakdown. Removal of the follicular tissue did not prevent the action of the steroid progesterone on the germinal vesicle. Steroids appear to act directly on the oocyte and calcium ions appear to be important for the biological action of the steroids.The author wishes to express his sincere appreciation to The Upjohn Co. for the support which greatly aided this study. The efforts of Dr. Albert Notation in preparation of sulfated steroids are also acknowledged.
78 citations
TL;DR: The amounts of secondary metabolites accumulated by in vitro cultures of plant cells have generally been disappointingly small and attempts to transform exogenous substrates by cultures of plants cells have not hitherto been much more successful.
Abstract: THE amounts of secondary metabolites accumulated by in vitro cultures of plant cells have generally been disappointingly small and attempts to transform exogenous substrates by cultures of plant cells have not hitherto been much more successful1.
52 citations
TL;DR: Six steroids with absorption maxima at 240 mμ secreted by the tissue culture system of a mouse adrenal cortex tumor have been extracted from the growth medium of the cultures and a seventh steroid, which does not absorb light, was found to have properties similar to those of 3β, 20α-dihydroxy-5- pregnene.
Abstract: Six steroids with absorption maxima at 240 mμ secreted by the tissue culture system of a mouse adrenal cortex tumor have been extracted from the growth medium of the cultures. 20α-Hydroxy-4-pregnen-3-one and 11β, 20α-dihydroxy-4-pregnen-3-one were identified on the basis of infrared spectra and chemical data. Three of the 4 other such compounds were tentatively identified as progesterone, 11β-hydroxyprogesterone, and 20a-hydroxy-4-pregnene-3,lldione. A seventh steroid, which does not absorb light at 240 mμ, was found to have properties similar to those of 3β, 20α-dihydroxy-5- pregnene. These steroids arise either upon ACTH stimulation, by incubation of the cultures withthe exogenous precursor pregnenolone, under basal conditions, or by all 3 modes of synthesis. The unique patterns of secretion observed in the tissue culture system result from the interaction of the adrenal specific properties still expressed by the adrenal tumor and the conditions of tissue culture that have caused, in some unknown manner...
50 citations
TL;DR: The results tend to indicate that progesterone is as good a precursor of cardenolides as pregnenolone, and it is suggested that the biosynthesis of cardanolides might proceed through the intermediacy of progester one.
Abstract: The incorporation of progestrone-7α-3H and pregnenolone-7α-3H into digitoxigenin, gitoxigenin, and digoxigenin in isolated, surviving leaves of Digitalis lanata was demonstrated. In addition, the conversion of pregnenolone to progesterone in the same system was proved. The results tend to indicate that progesterone is as good a precursor of cardenolides as pregnenolone It is suggested that the biosynthesis of cardenolides might proceed through the intermediacy of progesterone.
48 citations
TL;DR: Observations reported are considered to be compatible with increased activities of the microsomal enzymes in response to increase in the production of substrate (pregnenolone) under the influence of gonadotrophic stimulation.
44 citations
TL;DR: Pregnenolone and progesterone were estimated in extracts from adrenal glands of rats by gas— liquid chromatography by gas-liquid chromatography with error bars of 0.1.
Abstract: 1. Pregnenolone and progesterone were estimated in extracts from adrenal glands of rats by gas—liquid chromatography.
2. In unstressed rats their concentrations were found to be smaller than that of corticosterone.
3. Acute stress caused an increase in the concentrations of these steroids which paralleled that of corticosterone.
42 citations
41 citations
TL;DR: The biosynthetic activity of luteinizing hormone was significantly lowered per unit weight of the tissue, but the total activity per gland was nog significantly influenced by hexestrol treatment.
TL;DR: The capacity of fetal testes of a range of mammalian species to synthesize testosterone from steroidal precursors is established during fetal development and it is suggested that the capacity of the adult mammalian testes to synthesise C19 steroids, particularly testosterone, is established During fetal development.
TL;DR: After the administration of pregnenolone-4- 14 C to a Digitalis lanata plant, the following radioactive metabolites were isolated: digitoxigenin, gitoxigen in, digifologenin, 5β-pregnane-3,20-dione, and progesterone.
TL;DR: Neither ACTH, TSH nor prolactin could replace gonadotrophin in enhancing the cleavage reaction of the hypophysectomized animal and an inverse relationship was observed between rate of cholesterol sidechain cleavage and labeled amino acid incorporation into mitochondrial protein after gonadOTrophin treatment.
TL;DR: It was concluded that 11-deoxycortisol is a metabolite in importance equal to cortisol that can be transformed into cortisol using the homogenate technique.
Abstract: Whole homogenates (10%) of eel adrenocortical tissue were incubated with cholesterol- 7-3H and with mixtures of pregnenolone- 16-3H +progesterone-4-14C and progesterone-1,2- 3H +17α-hydroxyprogesterone-4-14C. Cholesterol gave rise to tritiated cortisol arid to a 3ubstance presumptively identified as pregnenolone-3H, while the 2 substrate pairs were partieily transformed to tritium and carbon-14 labeled cortisol and 11-deoxycortisol. The presence of corticosterone, aldosterone or 18-hydroxycorticosteronecould not be detected in either experiment. Analysis of the isotope content of the end-products suggested a relative lack of transformation of pregnenolone to progesterone. Quantitatively, the homogenate technique yielded transformation rates 100-fold higher than obtained by the use of adrenocortical tissue minces. It was concluded that, under these conditions, 11-deoxycortisol is a metabolite in importance equal to cortisol. (Endocrinology 81: 904, 1967)
TL;DR: A double isotope derivative method for the estimation of pregnenolone (3β-hydroxypregn-5-en-20-one) sulfate in plasma is described and values are as high as reported values for progesterone.
Abstract: A double isotope derivative method for the estimation of pregnenolone (3β-hydroxypregn-5-en-20-one) sulfate in plasma is described. Acetic-1-14C-anhydride is used as reagent and 7α-3H-ammonium pregnenolone sulfate as indicator. Multiple chromatographies before and after acetylation and recrystallization to constant 3H/14C are used to achieve purification. The mean recovery of the indicator is 9 ± 4%. The average absolute deviation of paired samples is 1.5 μg/100 ml. Pregnenolone sulfate can be measured in plasma throughout normal pregnancy. Values are as high as reported values for progesterone. A gradient is shown between fetal and maternal compartments (F > M) and between umbilical artery and umbilical vein (A >V).
TL;DR: The mechanism of side-chain cleavage during the course of steroid hormone biosynthesis by rat testicular and adrenal enzyme preparations has been investigated, and it was established that the oxygen atoms of the 17-ketone and 17β-hydroxyl groups of androstenedione and testosterone, respectively, which were derived by testicular enzymes from progesterone, originated from the 17α-Hydroxyl group of 17 α-hydroxyprogesterone.
TL;DR: The absence of any effect of testosterone, progesterone, androstenedione, pregnenolone and 17α-hydroxyprogesterone point to the specificity of the effect of cortisol in isolated rat-liver nuclei.
TL;DR: The results suggest that testosterone is made from pregnenolone and 17α-hydroxypregnenol one by a pathway independent of androstenedione.
TL;DR: A pathway is suggested for the biosynthesis of Delta(16)-steroids from pregnenolone in boar testis tissue and the possibility that progesterone may be an intermediate is discussed.
Abstract: 1. The metabolism of [4-(14)C]pregnenolone in vitro by boar adrenocortical and testis tissue has been studied. 2. Boar testis tissue formed three labelled Delta(16)-steroids, 5alpha-androst-16-en-3alpha-ol, 5alpha-androst-16-en-3beta-ol and androsta-4,16-dien-3-one. In adrenal tissue very much smaller yields of the same metabolites were obtained. 3. Both tissues produced labelled progesterone, androst-4-ene-3,17-dione and testosterone in varying quantities. The amount of progesterone was about 120 times greater in the adrenal tissue. In testis tissue dehydroepiandrosterone was found only in small quantity. 4. A pathway is suggested for the biosynthesis of Delta(16)-steroids from pregnenolone in boar testis tissue. The possibility that progesterone may be an intermediate is discussed.
TL;DR: The results suggest that adenosine 3',5'-cyclic phosphate stimulates corticosteroidogenesis by activating the mitochondrial enzymes which are rate-limiting in the utilization of cholesterol.
Abstract: Adenosine 3'5'-cyclic phosphate stimulated the conversion of added cholesterol to pregnenolone in "coupled" rat adrenal mitochondria provided with succinate, and in "leaky" mitochondria fortified with reduced nicotinamide adenine dinucleotide phosphate. Adenine nucleotides other than adenosine 3',5'-cyclic phosphate did not duplicate these actions. The cyclic nucleotide was also effective in supernatants from sonically disrupted mitochondria. The minimum effective concentration was 50 micromoles per liter or less. The results suggest that adenosine 3',5'-cyclic phosphate stimulates corticosteroidogenesis by activating the mitochondrial enzymes which are rate-limiting in the utilization of cholesterol.
TL;DR: An approx.
TL;DR: The results are interpreted as illustrating pathways of steroid biogenesis leading to the formation of 17-hydroxy-corticosteroids from both progesterone and pregnenolone, the latter via 17α-hydroxypregnenol one.
TL;DR: A kinetic study of the synthesis of corticosterone from [16-3H]-pregnenolone and [4-14C]-progesterone in sheep adrenals has indicated that the two precursors were handled differently, and its structure suggested that it might have acted as an alternative intermediary to progesterone.
TL;DR: Progesterone is a more effective inhibitor of mitochondrial respiration than the metabolically related steroids pregnenol one, pregnandione and allo-pregnanolone, and also than the artificial gestagens norprogester one, 4-hydroxy-17α-acetoxyprogestersterone, chlormadinone and 1-dehydrochlormadone.
TL;DR: Testes obtained at surgery from a male pseudohermaphrodite after 3 days of treatment with human chorionic gonadotropin and measurements of testosterone and androstenedione concentrations in spermatic venous blood were found to be in similar ratio to in vitro production.
Abstract: Labial testes were obtained at surgery from a male pseudohermaphrodite after 3 days of treatment with human chorionic gonadotropin (HCG). The testes were sliced and incubated with acetate-1-14C. The followihg radioactive steroids were identified and measured by reverse isotope dilution and characterized for radiochemical purity: 3β-hydroxy-Δ5-pregnen-20-one (pregnenolone), progesterone, 17-hydroxy-Δ4-pregnene-3,20-dione (17-hydroxyprogesterone), 3β-hydroxy-Δ5-androsten-17-one (DHA), Δ4-androstene-3,17-dione, testosterone, estradiol- 17β, and estrone. The synthesis in vitro of all steroids was augmented by human chorionic gonadotropin. Androgens were the major radioactive products found, testosterone being the principal steroid synthesized in vitro. Measurements of testosterone and androstenedione concentrations in spermatic venous blood were found to be in similar ratio to in vitro production. Urine and peripheral blood contained amounts of testosterone usually found in normal adult males. Incomp...
TL;DR: There is a highly significant correlation between the biosynthesis of these compounds and the urinary excretion of 11-deoxy-17-oxosteroids and 17-hydroxycorticosteroids as represented by a urinary discriminant function.