Showing papers on "Pregnenolone published in 1979"
TL;DR: The role of the adrenal gland in the polycystic ovary syndrome (PCO) was reassessed and significantly elevated basal levels of A, T, 17Po, and LH were found in the PCO group.
Abstract: The role of the adrenal gland in the polycystic ovary syndrome (PCO) was reassessed. A series of C19 and C21 steroids and pituitary hormones was investigated by measurements of serum cortisol, dehydroepiandrosterone (DHEA), an-drostenediol (Adiol), androstenedione (A), testosterone (T), pregnenolone (Pe), 17-hydroxypregnenolone (17Pe), progester-one (Po), 17-hydroxyprogesterone (17Po), DHEA sulphate, sex hormone-binding globulin (SHBG), LH, FSH, and PRL in nine normal women in the early follicular phase of the menstrual cycle and nine women with PCO. Fluctuations of C19 and their C21 precursors were determined during the 24-h endogenous ACTH swings. The responses to dexamethasone suppression and to subsequent stimulation with two small pulses (200 ng/1.5 m2) of ACTH (to assess adrenal sensitivity) and an infusion (20 μg/2 h) of ACTH (to assess adrenal capacity) were analyzed. Significantly elevated basal levels of A, T, 17Po, and LH were found in the PCO group. In the normal subjects, a circadian rhythm s...
159 citations
TL;DR: The topology of the steroid hydroxylase complexes in bovine adrenocortical mitochondria were studied by using controlled digestion with trypsin of purified inner mitochondrial membranes and strongly suggest that both cytochrome P-45011p and cyto chrome P-450,, are located on the matrix side of the mitochondrial inner membrane.
115 citations
TL;DR: The effects of angiotensin II (All), ACTH, and potassium on early and late steps of aldosterone biosynthesis were studied in collagenase-dispersed cells from rat adrenal capsules and dog zona glomerulosa to measure the formation of pregnenolone and later steps of biosynthetic conversion in the absence of endogenous precursors.
Abstract: The effects of angiotensin II (All), ACTH, and potassium on early and late steps of aldosterone biosynthesis were studied in collagenase-dispersed cells from rat adrenal capsules and dog zona glomerulosa. Isolated cells were incubated with a cyanoketone derivative (WIN 19,578) to isolate the nearly and late portions of the biosynthetic pathway. In this way, the formation of pregnenolone and later steps of biosynthetic conversion in the absence of endogenous precursors could be measured independently during stimulation by the three regulators. During incubation for 3 h with 10 nM All, 10 nM ACTH, or 15 mM potassium, marked stimulation of pregnenolone production was observed in glomerulosa cells of both species. In rat glomerulosa cells, each of the three regulators also stimulated conversion of exogenous corticosterone to aldosterone. In dog glomerulosa cells, All and potassium, but not ACTH, stimulated the conversion of corticosterone to aldosterone. In rat glomerulosa cells, aldosterone production from e...
105 citations
TL;DR: Testicular stimulation in vitro with a high dose of hCG resulted in significantly greater production of testosterone, pregnenolone, and estradiol by cryptorchid than by control rat tissue, probably as a result of down-regulation of LH receptors due to the 4-fold elevation of serum LH levels in the Cryptorchid rats.
Abstract: One month after the induction of cryptorchidism in adult rats, serum levels of LH and FSH were significantly elevated in comparison with sham-operated controls, whereas serum levels of testosterone remained low to normal. Testis weight in cryptorchid rats was reduced by over 66%, and once the extratubular fluid was removed by decapsulation, the reduction in weight was 78%. The basal production of testosterone, pregnenolone, and estradiol in vitro by testes from cryptorchid rats was similar to controls, whereas significantly less androstenedione was produced. Testicular stimulation in vitro with a high dose of hCG (360 pM) resulted in significantly greater production of testosterone, pregnenolone, and estradiol by cryptorchid than by control rat tissue. The in vitro binding of [125I]hCG per testis was decreased in the cryptorchid state to 40% of control values, probably as a result of down-regulation of LH receptors due to the 4-fold elevation of serum LH levels in the cryptorchid rats.
83 citations
77 citations
TL;DR: Self-suppression of adrenocortical cells suggests the existence of a mechanism for the find adjustment of steroidogenesis that operates in addition to the classical control exerted by the anterior pituitary.
Abstract: The relation between steroidogenesis induced by ACTH and that induced by exogenous concentrations of glucocorticoids was studied in isolated adrenocortical cells. Exogenous corticosterone and cortisol, in concentrations within the production capacity of the adrenal gland, suppressed steroidogenesis induced by ACTH in rat and beef cells, respectively. The precursors pregnenolone and progesterone enhanced steroidogenesis in both rat and beef cells. Aldosterone in rat cells and 17 beta-estradiol in rat and beef cells had little if any effect on steroidogenesis. Either suppression or stimulation by exogenous steroids was acute, that is, after 2-h incubation for rat cells and 1-h incubation for beef cells. A direct suppressive action of end product glucocorticoids is indicated. This observed self-suppression of adrenocortical cells suggests the existence of a mechanism for the find adjustment of steroidogenesis that operates in addition to the classical control exerted by the anterior pituitary.
60 citations
TL;DR: It was found that human fetal adrenal tissue maintained in organ culture secreted appreciable quantities of dehydroisoandrosterone sulfate (DS) and cortisol and plasma lipoproteins are a major source of the cholesterol utilized by the human fetal Adrenal for steroidogenesis.
Abstract: In the present investigation it was found that human fetal adrenal tissue maintained in organ culture secreted appreciable quantities of dehydroisoandrosterone sulfate (DS) and cortisol. Pregnenolone was also secreted in significant amounts, principally as the sulfate ester. The highest rate of secretion of these steroids by fetal adrenal tissue occurred when both ACTH and whole human serum were present in the culture medium. In the absence of ACTH, steroid secretion was low. When whole serum was replaced by lipoprotein-poor serum, the steroidogenic response to ACTH was markedly attenuated but not abolished. On the basis of these findings, it is concluded (1) that the human fetal adrenal can synthesize steroid hormones cte novo from cholesterol, (2) that ACTH is an important stimulant of steroidogenesis by the human fetal adrenal, and (3) that pTasma lipoproteins are a major source of the cholesterol utilized by the human fetal adrenal for steroidogenesis. Hence, it is likely that factors which regulate t...
59 citations
TL;DR: It is suggested that LH and cyclic AMP stimulate side-chain cleavage of cholesterol (and hence steroidogenesis) by a mechanism involving actin—presumably in microfilmaments; the responding microfilaments promote transport of cholesterol to mitochondria.
58 citations
TL;DR: The possibility of a local autoregulation of progesterone secretion involving circulating steroids and feedback inhibition was considered, and testosterone was infused into the ovarian arterial circulation to create locally high concentrations of inhibitory steroids, suggesting the absence of feedback regulation of progestersone production by circulating steroids at the ovarian level.
Abstract: The 3j3-hydroxy-�-steroid dehydrogenase/�15-�14-isomerase complex (IISO) is responsible for the conversion of pregnenolone to progesterone. In the ovine corpus luteum, HSD activity was found to be localized in the microsomal fraction and the activity displayed a broad p11 optimum between pH 6.5 and 8.0. The HSD activity was extremely sensitive to feedback inhibition by its own product, progesterone, and the inhibition appears to be competitive in nature. The inhibition could be relieved and pseudo-zero order kinetics established with the addition of normal serum to the reaction mixture. The steroid binding proteins in serum presumably bound the progesterone as it was produced. The affinity of HSD for progesterone (product) appears to be several fold higher than for pregnenolone (substrate). Testosterone and estradiol were also potent inhibitors of HSD activity. The inhibition of HSD activity by progesterone could be demonstrated in suspensions of isolated luteal cells. Since this phenomenon was observed in preparations of intact cells, the possibility of a local autoregulation of progesterone secretion involving circulating steroids and feedback inhibition was considered. To create locally high concentrations of inhibitory steroids, testosterone was infused into the ovarian arterial circulation. When this was done there was no effect on progesterone secretion, suggesting the absence of feedback regulation of progesterone production by circulating steroids at the ovarian level.
49 citations
TL;DR: Steroid alcohol sulphotransferases have not previously been obtained in a pure state possibly because of their inherent instability, and appear to be identical, as judged by fingerprint data of the tryptic peptides and the amino acid composition.
48 citations
TL;DR: It is concluded that in men the circadian rhythm of the major gonadal steroids is independent of the rhythm of adrenal steroids.
Abstract: The circadian variation in the levels of Cortisol (C), pregnenolone (Δ5P), 17-hydroxypregnenolone (17-HO-Δ5P), dehydroepiandrosterone (DHA), 20 α-dihydroprogesterone (20-HO-P), 17-hydroxyprogesterone (17-HO-P), androstenedione (A), testosterone (T), 5 α-dihydrotestosterone (DHT) as well as of the sulphurylated forms of pregnenolone (Δ5P-S), 17-hydroxypregnenolone (17-HO-Δ5P-S), dehydroepiandrosterone (DHA-S), testosterone (T-S) and dihydrotestosterone (DHT-S) was assessed, or re-assessed together with the levels of FSH and LH in peripheral blood samples collected from 12 healthy men at 3-hour intervals during 24 hours. The plasma levels of all unconjugated steroids and of Δ5P-S exhibited a significant circadian rhythm. No circadian variation was found in the levels of the other sulphurylated steroids or of FSH and LH. The relative amplitudes of the variation were: 17-HO-Δ5P: 310%, C: 290%, DHA: 210%, A: 170%, 17-HO-P: 110%, DHT: 73%, T: 65%, Δ5P-S: 59%, and 20-HO-P: 21%. The individual peak values of 17-HO-P, 20-HO-P, T and DHT were more scattered than those of C and A, or of the Δ5-steroids. A significant correlation was found between the levels of C, on the one hand, and those of Δ5P, 17-HO-Δ5P and DHA, on the other hand, and also between the levels of A and those of 17-HO-Δ5P and DHA. Furthermore, the levels of T were significantly correlated to those of 17-HO-P; however, no correlation was found between the levels of these two steroids and those of any other hormonal parameter studied. The insertion of a short catheter at 18.00 h resulted in an extra peak in C levels in 5 subjects. This was associated with a simultaneous peak in Δ5P, 17-HO-Δ5P, DHA and A levels, but not in those of 17-HO-P, T and DHT. It is concluded that in men the circadian rhythm of the major gonadal steroids is independent of the rhythm of adrenal steroids.
TL;DR: As with adrenocorticotropin pretreatment in vivo, addition of cardiolipin in vitro enhances adrenal mitochondrial pregnenolone synthesis and apparent binding of cholesterol to cytochrome P-450scc.
TL;DR: It is established that from the onset of estrogen synthesis the fetal ovary possesses all of the enzymes necessary to form estrogens from pregnenolone, including sufficient 3β-hydroxysteroid dehydrogenase-Δ4,5-isomerase activity.
Abstract: Two aspects of the differentiation of the fetal rabbit gonad have been studied. First, the ability of the fetal ovary to synthesize 17β-estradiol from [7-3H]pregnenolone was measured. By day 18 of gestation, the fetal ovary was capable of synthesizing 17β-estradiol from radioactive pregnenolone (5 mol 2 h-1 mg protein-1), thus establishing that from the onset of estrogen synthesis the fetal ovary possesses all of the enzymes necessary to form estrogens from pregnenolone, including sufficient 3β-hydroxysteroid dehydrogenase-Δ4,5-isomerase activity. Second, a method was developed to estimate the rate of cholesterol side chain cleavage activity by measuring the total amount of six steroids [progesterone, pregnenolone, dehydroepiandrosterone, androstenedione, Δ5-androstenediol (5-androstene-3β,17β-diol), and testosterone] produced in 2-h incubations of fetal rabbit gonads. Cholesterol side chain cleavage activity in fetal testes was linear with time up to 2 h and with increasing concentrations of hCG up to a ...
TL;DR: In this paper, it was suggested that one function of the high steroid glucuronide production by the teleost testis is to limit free 11-oxygenated androgen production to the environmentally favorable temperature for reproduction for the species.
TL;DR: It is indicated that acute elevation of oestradiol production is a contributory factor in the steroidogenic lesions of LHRH- and hCG-desensitized Leydig cells in the rat testis.
TL;DR: The results indicate the presence of the following biosynthetic enzyme systems in ovaries and pyloric caeca of Asterias rubens: a side-chain-cleaving enzyme complex and a Δ 5 –Δ 4 - isomerase -3β- HSD complex.
Abstract: 1. 1. In vitro biosynthesis of steroids from cholesterol in ovaries and pyloric caeca of Asterias rubens has been investigated. 2. 2. The formation of pregnenolone and progesterone was demonstrated in both tissues by using 1,2-3H-cholesterol as a precursor. 3. 3. Pregnenolone and progesterone are produced in small quantities; the ovaries appear to be more active in the biosynthesis of these steroids than the pyloric caeca. 4. 4. The results indicate the presence of the following biosynthetic enzyme systems in ovaries and pyloric caeca of Asterias rubens: a side-chain-cleaving enzyme complex and a Δ 5 –Δ 4 - isomerase -3β- HSD complex. 5. 5. The importance of these enzymes and the function of cholesterol for the biosynthesis of steroids will be discussed.
TL;DR: Using mass spectrometric, radioisotopic, chromatographic and chemical techniques, five fatty acid esters of 3 beta-hydroxy-5-pregnancy-20-one (pregnenolone) have been identified as components of the lipoidal derivatives biosynthesized in vitro with bovine adrenal mitochondria.
TL;DR: 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.
Abstract: 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.
TL;DR: The Leydig cell tumour used in this study can be used to investigate certain aspects of lutropin action where large quantities of cells are required.
TL;DR: Addition of precursors of sex hormones, such as pregnenolone, DHA, and Δ4-androstenedione to the culture media increases significantly steroid production, but in patterns appropriate with respect to the sexual differences observed in control gonads.
TL;DR: Endogenous steroid secretion and the conversion of exogenous pregnenolone and progesterone were studied in tissue culture of human mid-term fetal adrenal cells indicating that human fetal adrenals in spite of the lack of 3β-HSD are capable of synthesizing efficiently cortisol.
TL;DR: Pregnenolone and progesterone were shown to be formed from cholesterol and β-sitosterol in mitochondria prepared from human adrenals, testes and term placentae.
TL;DR: It is concluded that stress has a marked inhibitory action on gonadal function both in male and female baboons and inhibition of steroidogenetic function is exerted both on the ovarian follicles and on the corpus luteum.
Abstract: Adult baboons (5 males and 5 females) were exposed to immobilization stress by being strapped to a table in a horizontal position for 2 h. In females the experiment was performed during both the follicular and luteal phase. Peripheral blood was withdrawn at frequent intervals, the first sample just before immobilization, and the last one 3 days later. A number of steroids were measured in blood plasma samples by radioimmunoassay (17-hydroxypregnenolone, 17-hydroxyprogesterone, pregnenolone, testosterone, dihydrotestosterone, progesterone, 20alpha-dihydroprogesterone, oestone, oestradiol) or competitive protein binding (cortisol) techniques. The cortisol levels exhibited a marked increase in both sexes. This increase was observed already during the immobilization and lasted for approximately 24 h. A similar, even more pronounced increase was seen in 17-hydroxypregnenolone, 17-hydroxyprogesterone and pregnenolone levels. A marked, long-lasting (72 h) decrease of testosterone and dihydrotestosterone levels was a consistent finding in male baboons. This was not observed in the females which, on the other hand, exhibited a marked decrease (duration 48 h) of progesterone and 20alpha-dihydroprogesterone levels during the luteal phase, and a significant decrease (duration greater than 24 h) of oestradiol and oestrone concentrations during the follicular phase. It is concluded that stress has a marked inhibitory action on gonadal function both in male and female baboons. In females and inhibition of steroidogenetic function is exerted both on the ovarian follicles and on the corpus luteum.
TL;DR: This is the first direct evidence that Sertoli cells have the capacity to synthesize steroids de novo from acetate, as shown in rats from 17 day old rats.
TL;DR: In vitro studies demonstrated the presence of the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD) in the dorsal body complex, ovotestis and buccal ganglia of Helix pomatia and the relative importance of the pathways in steroidogenesis followed in the organs studied is discussed.
Abstract: 1. 1. In vitro studies demonstrated the presence of the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD) in the dorsal body complex, ovotestis and buccal ganglia of Helix pomatia. 2. 2. Results of incubations with tritiated pregnenolone and tritiated dehydroepiandrosterone indicate substrate specificity of the 3β-hydroxysteroid dehydrogenase. 3. 3. The activity of the two 3β-hydroxysteroid dehydrogenases vary independently of each other during different physiological states of the animal. 4. 4. Before oviposition the conversion of dehydroepiandrosterone into androstenedione in all tissues investigated exceeds that of pregnenolone into progesterone. On the contrary, after oviposition this is reversed for the ovotestis. 5. 5. The relative importance of the pathways in steroidogenesis followed in the organs studied is discussed.
TL;DR: Log (P) and log (20P) concentration-time curves describe single segment linear curves of similar slope and are consistent with the hypothesis that 20P is a metabolite of P, sharing in a relatively stable interconversion with P as the major placental secretory pr...
Abstract: This report describes aggregate time trend effects of advancing gestational age on circulating maternal concentrations of progesterone (P), 16α-hydroxyprogesterone, 17α-hydroxyprogesterone (17P), 20α-dihydroprogesterone (20P), Δ5-pregnenolone sulfate, Δ5-pregnenolone (Δ5P), and 17-hydroxyΔ5-pregnenolone (17Δ5P) in a sequential series of 153 blood samples obtained from 19 normal pregnant women ranging from 26-40 weeks gestational age. After logarithmic transformations and curve-fitting procedures, significant differences in slopes were sought and tested by multivariate least squares methods. All steroids, except for 17Δ5P, were markedly elevated above previously reported nonpregnancy concentrations and plotted as positive sloping curves. Log (P) and log (20P) concentration-time curves describe single segment linear curves of similar slope (P > 0.05) and are consistent with the hypothesis that 20P is a metabolite of P, sharing in a relatively stable interconversion with P as the major placental secretory pr...
TL;DR: These results, noting also the low cholesterol content of the tumor cells, suggested that the lack of availability of cholesterol was the factor responsible for the poor steroidogenic response of the cells to ACTH.
Abstract: ACTH produced a 75% increase in pregnenolone biosynthesis from endogenous precursors in isolated cells prepared from the rat Snell adrenocortical carcinoma 494. On the addition of 24- and 25-hydroxycholesterol to the tumor cells, the rate of pregnenolone synthesis increased 10-fold but was insensitive to the presence of ACTH. Addition of lipoprotein cholesterol resulted in increased pregnenolone biosynthesis when ACTH was present. High density lipoprotein cholesterol appeared to be internalized and used for steroidogenesis preferentially to low density lipoprotein cholesterol. The cholesterol ester hydrolase activity of the cytosolic fraction of the tumor was found to be extremely low compared to that of the normal adrenal cell. These results, noting also the low cholesterol content of the tumor cells, suggested that the lack of availability of cholesterol was the factor responsible for the poor steroidogenic response of the cells to ACTH. The major steroid product of the tumor cells was determined to be ...