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Results for “17-alpha-Hydroxypregnenolone”

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At least 19 recordsLinked to original sources
PubMed1975

Studies of in vitro steroid metabolism by testis tissue from 'complete' and 'incomplete' forms of testicular feminization.

The in vitro steroid metabolism of testicular tissue from seven cases of testicular feminization was studied. Using radioactive steroid substrates of both C21 and C19 configurations, kinetic studies of these tissues showed that the major pathway of testosterone production was via the delta5 pathway, i.e. pregnenolone leads to 17 alpha-hydroxypregnenolone leads to dehydroepiandrosterone leads to androstenedione and androstenediol leads to testosterone, with the accumulation of dehydroepiandrosterone and androstenediol. This accumulation of dehydroepiandrosterone and androstenediol does not occur in similar incubations of normal human testis tissue. The seven cases of testicular feminization were classified as 'complete' or 'incomplete' forms of the syndrome by reference to clinical data and the histology of the testicular tissue. It was concluded that the biochemical differences between the two forms of the syndrome were the greater production and accumulation of C21 and C19 delta 4 steroids from the C21 and C19 delta 5 steroid precursors indicating the relatively greater activity of the C21-3beta-hydroxysteroid dehydrogenase-isomerase enzyme in the 'incomplete' form.

17-alpha-Hydroxypregnenolone↗
PubMed1975

Cutaneous hydroxystereoid dehydrogenases and rat-hair cycle.

The histochemical activity pattern of a number of hydroxysteroid dehydrogenases was studied during a provoked hair cycle in the rat skin. The intensity of reaction was high with dehydroepiandrosterone, estradiol, androsterone and pregnenolone, and none with 11-beta-hydroxyprogesterone, testosterone, dihydrotestosterone, 17-alpha-hydroxypregnenolone and 17-alpha-hydroxyprogesterone. Reactivity also varied with the hair cycle. The reactive sit-s were the acini of sebaceous glands and the hair sheaths.

17-alpha-Hydroxypregnenolone↗
PubMed1979

Testosterone and its precursors and metabolites enhance guanylate cyclase activity.

Both testosterone and cyclic GMP stimulate DNA synthesis. Because cyclic GMP and testosterone seem to have similar actions, the objective of this investigation was to determine if testosterone and its precursors might have part of their mechanism of action through stimulation of guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2], the enzyme that catalyzes the formation of cyclic GMP from GTP. The precursors--namely, progesterone, pregnenolone, 17 alpha-progesterone, 17 alpha-hydroxypregnenolone, androstenedione, and dehydroepiandrosterone--caused a 2- to 3 1/2-fold enhancement of guanylate cyclase activity in rat liver, kidney, skeletal muscle, and ventral prostate at a concentration of 1 microM. These precursors are generated from cholesterol, which had no effect itself on guanylate cyclase activity. Testosterone, 19-nortestosterone, 17-methyltestosterone, and 5 alpha-dihydrotestosterone enhanced guanylate cyclase activity 2- to 5-fold in the same tissues at 1 microM. Etiocholanolone, androsterone, and epiandrosterone, metabolites of testosterone metabolism, enhanced guanylate cyclase activity 1 1/2- to 2-fold at this same concentration. Dose-response relationships revealed that testosterone and its precursors and metabolites had their maximal effect at 1 microM but still had some effect at 0.001 microM. The data in this investigation suggest that the guanylate cyclase-cyclic GMP system plays a role in the mechanism of action of testosterone and its precursors.

Animals↗
PubMed1978

[Nature of changes in the level of steroid hormones and their precursors in peripheral blood of Papio monkeys under stress].

The radioimmunological method was applied to determination of changes in the peripheral blood plasma level of 12 steroids in male Papio hamadryas under immobilization and surgical stress. Androgen content decreased, and the concentration of steroid hormone precursors and hydrocortisone blood plasma content rose in response to stress. These changes were in contraphase with the circadian steroid rhythms. The most objective and sensitive criteria of the stress situation evaluation were decrease of testosterone and dihydrotestosterone level, increase of pregnenolone concentration, as well as of 17-alpha-hydroxypregnenolone, 17alpha-hydroxyprogesterone in the blood plasma.

Androgens↗
PubMed1975

Studies on steroids in urine of the male newborn.

Four different methods of isolation and purification were utilized to study steroids in urine of male newborns which was collected during the first 5 days of life. These methods included celite column, ion exchange column and thin-layer chromatography, solvolysis and enzyme hydrolysis with beta-glucuronidase and aryl sulfatase. Procedural losses were evaluated by using radioactive internal standards. Final quantitation of each steroid was achieved by comparison of its chromatographic and quantitative behavior with the respective standard steroids on various gas-liquid chromatography systems, either as parent compound or as trimethylsilyl ether derivative. The following steroids were found in the amounts indicated: progesterone, 2.1 mug/1 (pool I), 4.6 mug/1 (pool III); pregnanediol, 625.0 mug/1 (pool IIa), 605.0 mug/1 (pool IIb glucuronide), 25.4 mug/1 (pool IIb sulfate), 4.2 mug/1 (pool IIb free), 729.0 mug/1 (pool III); 16alpha-hydroxyprogesterone, 713.0 mug/1 (pool III), 16alpha-hydroxypregnenolone, 14,000.0 mug/1 (pool III); 16alpha-hydroxydehydroepiandrosterone, 2,350.0 mug/1 (pool III); 16-dehydroprogesterone, 155.0 mug/1 (pool I), 21.2 mug/1 (pool IIb glucuronide), 97.5 mug/1 (pool IIb sulfate), 5.3 mug/1 (pool III); 16-dehydropregnenolone, 382.0 mug/1 (pool I), 1,380 mug/1 (pool IIb glucuronide), 172.0 mug/1 (pool IIb sulfate), 174.0 mug/1 (pool III); 16-dehydropregnanolone, 8.3 mug/1 (pool I), 239.0 mug/1 (pool IIb sulfate). Pregnenolone, pregnanolone, 17alpha-hydroxyprogesterone and 17alpha-hydroxypregnenolone could not be detected. The results support the concept that the steroid patterns of urine of the newborn and amniotic fluid are very similar and that the amniotic fluid steroid content is mainly dependent on fetal urinary steroid excretion. The data on delta16-C21-steroids are discussed.

17-alpha-Hydroxypregnenolone↗
PubMed1977

Origin of urinary 16 beta-hydroxydehydroepiandrosterone in essential hypertension.

The excretion rates and precursors of the 3-sulfate and glucuronide conjugates of 16 beta-hydroxydehydroepiandrosterone (16 beta-OH DHEA) were measured in normotensive controls and in patients with normal and low renin essential hypertension. The hypertensive subjects, and to the greatest degree those of the low renin subgroup, excreted increased amounts of 16 beta-OH DHEA sulfate and glucuronide and lesser amounts of DHEA sulfate and glucuronide than the controls. The major precursor of the urinary 16 beta-OH DHEA sulfate in the hypertensives was circulating DHEA sulfate, whereas the major precursors of 16 beta-OH DHEA glucuronide were DHEA, DHEA sulfate and 17-OH pregnenolone, as determined from their specific activities. Furthermore, both subgroups of hypertensives had similarly elevated DHEA and DHEA sulfate secretory rates compared to the controls. The stimulus to this increased peripheral conversion of circulating 17-OH pregnenolone, DHEA and DHEA sulfate into 16 beta-OH DHEA conjugates in essential hypertension, especially of the low renin type, is unknown.

17-alpha-Hydroxypregnenolone↗
PubMed1975

Steroid hormone formation in bovine ovarian follicles.

In an attempt to assess histophysiological implication of the follicular compartment of the bovine ovary in steroid hormone formation and the effect of human chorionic gonadotropin (hCG) in vitro on follicular steroidogenesis, minces of follicular tissues from non-gravid bovine ovaries were incubated with radioactive testosterone or acetate in the presence and absence of hCG. Significant amounts of estrone and estradiol-17beta were formed on incubation with testosterone-4-14C; hCG decreased the conversion approximately by 30%. The major radioactive products formed from acetate-l-14C were androstenedione and testosterone with lesser amounts of dehydroepiandrosterone and 17-hydroxyprogesterone. In addition, small amounts of progesterone, 17-hydroxypregnenolone, estrone and estradiol-17beta were formed. Histology of the dissected follicle specimens was characterized by dominant theca cells undergoing luteinization with small amounts of granulosa cells, which showed neither proliferation nor luteinization. The pattern of distribution of radioactivity among the steroids formed from acetate-14C was considered to represent steroidogenic profile of bovine atretic follicles. The addition of hCG in vitro increased the overall incorporation of radioactive acetate into the steroids approximately by 50%, although the range of increase was not uniform in the individual steroids under the exprimental conditions.

17-alpha-Hydroxypregnenolone↗
PubMed1976

Steroid hormone formation in human ovarian follicles in vitro.

Ovarian follicles of 5 to 15 mm in diameter were isolated from 45 ovaries of 34 patients in the follicular and luteal phases of the cycle. Three experiments were done. In the first, follicles were minced and incubated in Krebs-Ringer bicarbonate buffer containing 1 to 2muCi of testosterone-4-14C in the presence or absence of 100 IU human chorionic gonadotropan (hCG). In the second, minced follicles were incubated with 100 muCi of sodium acetate-I-14C under identical conditions. In the third, ten follicles from a single patient in the late proliferative stage of endometrial dating were cut in halves and incubated with 100 muCi of acetate-I-14C under identical conditions. The minced follicle preparation was capable of aromatizing testosterone-4-14C into radioactive estrone and estradiol in significant amounts. Incorporation of radioactive acetate into pregenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, estradiol and estrone was assessed by reverse dilution analysis with recrystallization to constant specific activity. The major radioactive products formed were androstenedione and 17-hydroxyprogesterone in the latter two experiments. Dehydroepiandrosterone was one of the major steroids in the second experiment. The minor products were testosterone, progesterone and pregnenolone. Smaller, but definite incorporations of radioactive acetate into estradiol and estrone occurred in the second experiment. On histological examination, the follicles were characterized by atretic changes. This distribution pattern of radioactive acetate among the steroids was considered to represent the steroidogenic profile of unstimulated or atretic follicles.

17-alpha-Hydroxypregnenolone↗
PubMed1976

Pathways of testosterone synthesis in decapsulated testes of mice.

In order to study the temporal relations in the biogenesis of testosterone, decapsulated testes of adult mice were incubated with carbon-14-labelled sodium acetate and attempts were made to isolate the most likely intermediates. Considerable quantities of radiochemically homogeneous squalene, lanosterol, cholesterol, testosterone and androstenedione, but no pregnenolone, progesterone, 17-hydroxypregnenoline, 17-hydroxyprogesterone, dehydroepiandrosterone, pregnenolone sulphate or dehydroepiandrosterone sulphate were isolated. The same pattern of incorporation was found when gradually increasing amounts of non-labelled pregnenolone, progesterone, 17-hydroxypregenenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, dehydroepiandrosterone sulphate or testosterone were added to the system as "trapping agents" or when Leydig cell preparations rather than decapsulated testes were used. The presence of 10 mIU of HCG greatly enhanced the de novo formation of testosterone, androstenedione and 5alpha-dihydrotestosterone but did not change the pattern of acetate incorporation. Radioimmunoassays of the incubation medium with or without added HCG, and carried out at different periods of time indicated the presence of gradually increasing amounts of testosterone and androstenedione together with some 5alpha-dihydrotestosterone, whereas only trace amounts of pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone and dehydroepiandrosterone were present. An analysis of the incubated testes revealed that the addition of HCG significantly enhanced the content of testosterone, androstenedione and 5alpha-dihydrotestosterone. Little or no increase was observed as far as pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone or dehydroepiandrosterone were concerned. It is concluded that decapsulated testes of mice synthesize de novo testosterone from sodium acetate under conditions in which the formation of pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, pregnenolone sulphate and 17-hydroxypregnenolone sulphate cannot be demonstrated.

17-alpha-Hydroxypregnenolone↗
PubMed1976

Hormonal changes during the menstrual cycle of the baboon (Papio hamadryas).

Eleven unconjugated steroids were measured daily during a complete cycle in the peripheral plasma of 6 normally menstruating baboons (Papio hamadryas) by means of a radioimmunoassay procedure and the levels were compared with those found previously in 17 normally menstruating women. The patterns of progesterone and 20alpha-dihydroprogesterone were very similar to those found in women throughout the entire menstrual cycle. However, the ratio of these steroids differed markedly from that found in women. A great similarity of the follicular phase and the peri-ovulatory period profiles was observed in both species for 17-hydroxy-progesterone, pregnenolone, androstenedione, oestradiol and oestrone. The pattern of oestradiol:oestrone ratios was similar in both species. However, an elevation of the above five steroids, typical for the human luteal phase, was not found in baboons. The increase of testosterone values, seen in women at mid-cycle, was not detected in baboons. The plasma concentrations were lower in baboons than in humans for all the above steroids.

17-alpha-Hydroxypregnenolone↗
PubMed1976

Plasma levels of unconjugated steroids in male baboons (Papio hamadryas) and rhesus monkeys (Macaca mulatta).

In an attempt to find suitable animal models to aid in the study of the reproductive processes of the human male, plasma levels of unconjugated pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, 20alpha-dihydroprogesterone, 17-hydroxyprogesterone, androstenedione, testosterone, dihydrotestosterone, oestrone and oestradiol were measured in 18 male baboons and 10 male rhesus monkeys and the steroid levels were compared with those previously established in normospermic, middle-aged men. Significant species differences were found with regard to the three delta5-steroids studied; whereas the approximate relationship of pregnenolone to 17-hydroxypregnenolone and dehydroepiandrosterone was 1:2:4 in men, the corresponding relationship was 1:5:30 in rhesus monkeys and 1:10:10 in baboons. Similar levels of 20alpha-dihydroprogesterone were found in the three species. On the other hand, the 17-hydroxyprogesterone levels in baboons were much lower and the levels of androstenedione lower than those found in men and in rhesus monkeys. No species difference was found with regard to circulating testosterone levels. However, both rhesus monkeys and baboons exhibited much higher levels of dihydrostestosterone than did men. Oestrone levels were higher in baboons than in men and oestradiol levels were higher in rhesus monkeys than in men and in baboons. The significant differences in circulating steroid levels suggest that further studies (including i.a. steroid analyses in testicular tissue, seminal plasma and spermatic artery and vein following both stimulation and suppression of testicular endocrine function) are required before preference can be given to any of the two species studied as a suitable animal model for the study of new fertility regulating agents.

17-alpha-Hydroxypregnenolone↗
PubMed1977

Studies on the pattern of circulating steroids in the normal menstrual cycle. Circadian variation in theperi-ovulatory period.

Circadian variations of the plasma levels of dehydroepiandrosterone, 17-hydroxypregnenolone, pregnenolone and testosterone were investigated by radioimmunoassay in 10 normally menstruating women during the periovulatory period. In seven of the subjects it was also possible to estimate androstenedione and dihydrotestosterone levels. Blood was withdrawn continuously over a period of 48 h at a rate of 4 ml/h by means of a non-thrombogenic pump. The circadian rhythm was studied during 13 3-hour sampling periods (36 h) which were identical in all subjects. Dehydroepiandrosterone, 17-hydroxypregnenolone and pregnenolone showed a marked circadian rhythm with highest mean levels in the morning between 06.00 and 0.900 h and lowest mean levels during the night between 21.00 and 24.00 h. The peak levels of individual subjects coincided completely with the highest mean levels in the case of dehydroepiandrosterone, in 9 out of 10 cases with regard to 17-hydroxypregnenolone and in 8 of 10 cases as far as pregnenolone levels were concerned. The lowest individual levels were more dispersed around the means than were the individual peaks. The difference between the highest (morning hours: 06.00-09.00) and lowest (evening hours: 21.00-24.00) geometeric mean values was 404% for 17-hydroxypregnenolone, 163% for dehydroepiandrosterone and 71% for pregnenolone. The mean testosterone levels also exhibited an elevation between 06.00 and 09.00 h which was significant (P less than 0.05). However, the individual peak values were scattered from 21.00 h of the first day to 18.00 h of the second day. The mean concentrations of androstendine showed a significant increase between 06.00 and 18.00 h. The individual peaks were widely dispersed. Hence a uniform circadian rhythm correlated to the levels of the 5-steroids mentioned above could not be demonstrated in the case of testosterone and androstenedione. An analysis of variance indicated no significant differences between sampling periods as far as dihydrotestosterone levels were concerned. The extent and regularity of the circadian variation in the plasma levels of the 5-steroids studied makes it mandatory to standardize very carefully the exact time of blood withdrawal in any longitudinal study. In view of the sharp changes in the plasma levels during the morning hours, it is suggested that sampling during the afternoon period may provide more constant values.

17-alpha-Hydroxypregnenolone↗