Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Steroidogenesis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1978

Regulatory role of guanosine 3',5'-monophosphate in adrenocorticotropin hormone-induced steroidogenesis.

The relation between steroidogenesis induced by adrenocorticotropic hormone and the concentrations of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) was studied at different time intervals in isolated adrenal cells. Submaximal and supramaximal steroidogenic concentrations of the hormone did not cause detectable changes in cyclic AMP during the first 30 minutes, whereas there was an increase in the concentration of cyclic GMP that was accompanied by phosphorylation and steroidogenesis. It is therefore suggested that cyclic GMP, rather than cyclic AMP, is the physiological mediator of adrenocorticotropic hormone-induced adrenal steroidogenesis.

Adrenal Glands↗
PubMed1977

Reevaluation of the role of cyclic adenosine 3',5'-monophosphate and protein kinase in the stimulation of steroidogenesis by luteinizing hormone in bovine corpus luteum slices.

Incubation of bovine corpus luteum slices at 37 C with luteinizing hormone showed that 10.0 microng LH/ml caused a maximum rise in tissue cyclic AMP content within 15 min. Slices incubated with 1.0 or 0.1 microng LH/ml showed a much more gradual accumulation of this nucleotide. In the absence of added LH, a marked decline in the amount of cyclic AMP was observed during the first 60 min. The possible role of cyclic AMP in the action of LH was reexamined by studying the dose-response effect of LH on the stimulation of progesterone synthesis, cyclic AMP-dependent protein kinase activation, and cyclic AMP accumulation. After a 2-h incubatin, the results showed that the dose required to elicit a minimal significant stimulation of steroidogenesis was 0.01 microng/ml LH. At this and higher concentrations of LH, a concomitant stimulation of protein kinase activity and progesterone synthesis was also consistently observed. However, significant accumulation of cyclic AMP became consistently detectable only at 0.1 microng/ml LH. This report is the first to show a positive correlation between the activation of cyclic AMP-dependent protein kinase and the stimulation of steroidogenesis in the corpus luteum at the same minimal effective level of LH. These results indicate that cyclic AMP and the cyclic AMP-dependent protein kinase probably play important intermediary roles in the stimulation of steroidogenesis by LH in the bovine corpus luteum.

Animals↗
PubMed1977

Danazol inhibits steroidogenesis in the rat testis in vitro.

The effects of danazol on steroidogenesis in vitro in the rat testis were examined by studying: 1) androgen synthesis in rat Leydig cells cultured with danazol, 2) danazol binding to rat testis microsomal cytochrome P-450, and 3) enzyme kinetics of danazol inhibition of the microsomal enzymes of testicular steroidogenesis. Concentrations of danazol as low as 1 micrometer suppressed LH-stimulated testosterone and androstenedione production in cultured Leydig cells. The addition of danazol to a preparation of testicular microsomes elicited a type I cytochrome P-450 binding spectrum, with an apparent spectral dissociation constant (Ks) of 4.8 micrometer. Danazol inhibited progesterone and 17alpha-hydroxy-progesterone binding to microsomal P-450 with apparent spectral inhibition constants of 2.4 micrometer and 2.8 micrometer, respectively. Danazol competitively inhibited 3beta-hydroxy-delta5-steroid dehydrogenase-isomerase (apparent enzymatic inhibition constant, KI = 5.8 micrometer), 17alpha-hydroxylase (KI = 2.4 micrometer), 17,20 lyase (KI = 1.9 micrometer), and 17beta-hydroxysteroid dehydrogenase (KI = 4.4 micrometer). These findings indicate that low concentrations of danazol directly inhibit steroidogenesis in the rat testis in vitro.

Androgens↗
PubMed1979

Inhibitory effects of corticosterone on cell proliferation and steroidogenesis in the mouse adrenal tumor cell line Y-1.

Monolayer cultures of mouse adrenal tumor cell line Y-1 have been used to investigate the effects of glucocorticoid on cell replication, [3H]thymidine incorporation into the trichloroacetic acid-precipitated cell fraction, steroidogenesis, and the ACTH receptors of adrenocortical cells. Corticosterone at a concentration of 5.0--50 micrograms/ml inhibited cell replication and [3H]thymidine incorporation into trichloroacetic acid-precipitated cell fraction in a dose-related manner. Corticosterone at a concentration of 0.5--50 micrograms/ml inhibited ACTH-induced steroidogenesis in a dose-related manner. Steroids which do not possess glucocorticoid action did not show such inhibitory effects on cell replication and steroidogenesis of Y-1 cells. The characteristics of the ACTH receptors of these cells remained unaffected by corticosterone. Our findings suggest that synthesized or secreted glucocorticoid may play an important role in the direct regulation of proliferation and function of adrenocortical cells under physiological conditions.

Adrenal Gland Neoplasms↗
PubMed1975

Effect of luteinizing hormone and cyclic adenosine 3',5'-monophosphate on steroidogenesis in the ovarian follicle of the rabbit.

Mature ovarian follicles have been isolated from estrus rabbits and the effects of gonadotropin and cyclic AMP on steroidogenesis in this tissue determined. Gonadotropins used include LH, FSH, and prolactin; follicular levels of progesterone, 17-hydroxyprogesterone, testosterone and 17beta-estradiol in all experiments were quantitated by radioimmunoassay. Incubation of follicles with LH in concentrations ranging from 0.05 to 50 mug/ml medium yielded increases in the total ng steroid/follicle. Five mug LH/ml gave a maximal response with no further increase in steroid concentration when the LH was raised to 50 mug/ml. Prolactin had no effect on follicular steroidogenesis while the stimulatory action of a FSH preparation could only be partially attributed to LH contamination. Cyclic AMP also proved to be a potent stimulatory agent in follicular steroidogenesis with maximal increases at 20 mumoles/ml and a decline in the ng steroid/follicle when cyclic AMP was raised to 30 and 40 mumoles/ml. The effects of LH and cyclic AMP proved to be nonadditive; incubation of follicles simultaneously with 5 mug LH/ml and 20 mumoles cyclic AMP/ml yielded steroid concentrations which were no different than levels following incubation with either agent alone. Taken together, these results demonstrate that both LH and cyclic AMP cause increases in radioimmunoassayable steroid in the rabbit follicle in vitro and that LH probably acts by way of a cyclic AMP intermediate.

Animals↗
PubMed1976

Studies on oxidative phosphorylation and steroidogenesis by ovarian mitochondria after gonadotropic stimulation.

No differences in oxidative phosphorylation or in the per cent of [4-14C]progesterone were found in ovarian mitochondria of immature rats after treatment with 20 IU of pregnant mare serum gonadotropin (PMSG) iv 30 min before killing. However, treatment of immature rats with 20 IU of PMSG sc 54 h prior to killing decreased the ADP:O ratio and increased the per cent of [4-14C]cholesterol conversion. Electron microscopic studies showed that mitochondria with lamellar cristae were prominent in ovaries of untreated rats, while large pleomorphic mitochondria and mitochondria with tubulovesicular cristae dominated in ovaries of PMSG-treated rats. Ovarian homogenates separated by zonal centrifugation showed three peaks od cytochrome oxidase activity which shifted to the heavier end of the gradient after PMSG treatment. These studies suggest that PMSG treatment influences ovarian mitochondria, possibly by stimulating the synthesis of additional functional components and/or the biogenesis of new mitochondria. Aminoglutethimide addition to bovine luteal mitochondria decreased steroidogenesis by 60% when succinate was used as substrate. However, there was a 16% increase in the ADP:O ratio, apparently due to a decrease in oxygen utilization. When oligomycin was added to luteal mitochondria, there was a 30% decrease in the ACP:O ratio but a 300% increase in [4-14C]cholesterol conversion. Dinitrophenol also decreased mitochondrial steroidogenesis. These results suggest that energy obtained from succinate oxidation can be diverted from phosphorylation to support steroidogenesis.

Age Factors↗
PubMed1976

[Preovulatory changes of steroidogenesis in isolated rabbit follicles (author's transl)].

In an attempt to investigate the effect of ovulating hormone on the steroidogenesis of mature follicles in the course of ovulation, transitory changes of steroidogenesis in isolated rabbit follicles have been studied at several intervals after injection of an ovulatory dose of human chorionic gonadotropin (hCG). Five to ten follicles of approximately 1-2 mm in diameter were isolated from ovaries of a mature rabbit (2.5-3.0 kg) under streomicroscope, before and at the 3rd, 6th, 9th and 12th hours after intravenous injection of of 100 IU/kg of hCG. Follicles were incubated with 100 muCi of acetate-1-14C in 2 ml of Krebs-Ringer bicarbonate buffer (pH 7.4) at 37 degrees C for 3 hours under 95% oxygen plus 5% carbon dioxide. Each incubation was terminated by quick freezing and stored forzen at -20 degrees C until eighty follicles had been collected for each time period before commencement of analysis. Incorporation of radioactive acetate into pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone., 20 alpha-dihydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone and estradiol-17beta were analysed by the reverse dilution technique and identified in radiochemically pure form by recrystallization to constant specific activities. The steroidogenic activity of the follicles was evaluated by overall as well as fractionated incorporations. A peak in the overall incorporation of 14C- acetate into the ten steroids at the 3rd hour after hCG injection, followed by gradual decrease up to the 9th hour was observed. The incorporation decreased markedly to a minimum level at the 12th hour after hCG injection, which was below the level of preinjection control. Comparable quantitative fluctuations were found with the fractionated incorporation of 14C-acetate into the C21 and C18 steroids in the time sequence following hCG injection. However, the fractionated incorporation into C19 steroids reached to a maximum at the 6th hour after hCG injection. 5istribution patterns of incorporation among the individual steroids were varied at each interval of time. In the non-injected control, mature follicles synthesized predominantly estradiol-17beta, testosterone and androstenedione. Divergent steroids were formed from radioactive acetate at the 3rd hour after hCG injection. These included porgestogen, androgen and estrogen, but pregnenolone and 17hydroxyprogesterone were the two principal steroids produced. There was no essential difference in the steroidogenic patterns between the 6th and 9th hour, the major products being C21 and C19 steroids such as pregnenolone, 17hydroxyprogesterone, dehydroipiandrosterone and testosterone. The three androgens were the major steroids formed at the 12th hour after hCG injection. Thus the chages in the steroidogenic profile of the follicle was obvious in the course of ovulation. The basis of qualitative changes in follicular steroidogenesis during the process of ovulation have been discussed in connection with an accompanying effect of an ovulatory dose of hCG.

Acetates↗
PubMed1975

Concerning the relationship between protein synthesis and adenosine-3',5'-cyclic phosphate-stimulated steroidogenesis in isolated rat adrenal cells.

Inhibitors of protein synthesis decrease protein synthesis in isolated rat adrenal cells to a greater extent than they decrease adenosine-3',5'-cyclic phosphate (cyclic AMP)-stimulated steroidogenesis. At low concentrations of the inhibitors, varying degrees of recovery of the rate of steroidogenesis occurs with increasing time of incubation. As the concentration is increased, the time required to achieve any recovery of the rate of steroidogenesis increases and the extent of recovery decreases. The recovery also depends on the amount of cyclic AMP present. During the process of recovery the inhibition of protein synthesis continues in a linear manner. An explanation consistent with these data involves a rapidly turningover protein, the concentration of which is independent of the level of cyclic AMP present. However, the extent of transformation of this protein to an active form depends on the concentration of cyclic AMP.

Adrenal Cortex↗
PubMed1976

Therapy of dimethylbenzanthracene-induced mammary carcinomas in the rat by selective inhibition of steroidogenesis.

The effects of cyanoketone, a specific inhibitor of steroidogenesis at the levels of 3beta-hydroxysteroid oxidoreductase-dealta54-3-ketosteroid isomerase, the combination of cyanoketone with corticosterone, and corticosterone alone on the growth of dimethylbenzanthracene-induced hormone-dependent breast cancers in rats were compared with that produced by ovariectomy. Cyanoketone produces about as many regresssions of these cancers as does ovariectomy. However, cyanoketone with corticosterone results in a significant regression of tumors in all animals tested. This therapy also causes regression of significantly more tumors that are large at the beginning of treatment than does ovariectomy. These findings suggest that this kind of reversible blockade of steroidogenesis may be useful as a diagnostic tool in assessing the hormone dependence of breast tumors and as a possible therapeutic approach in the treatment of such tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1975

Endotoxic lipopolysaccharides stimulate steroidogenesis and adenylate cyclase in adrenal tumor cells.

Lipopolysaccharides (endotoxins) from Escherichia coli, Serratia marcesens and Salmonella typhosa stimulated steroid production in Y-1 adrenal tumor cells in culture with a latent period of 3-4 h. Lipid A, derived from Escherichia coli lipopolysaccharide, also stimulated steroidogenesis. Lipopolysaccharides and lipid A also stimulate adenylate cyclase activity and cause rounding of the cells. In contrast, lipopolysaccharides do not stimulate steroidogenesis in receptor-deficient adrenal tumor cells (OS-3) or Leydig tumor cells (I-10). This tends to rule out contamination by enterotoxin to which these lines respond. Although both hormone and lipopolysaccharide responses are lost in these lines, there was no interaction between these sites as judged by the failure of lipopolysaccharides to block, during their latency, the response to corticotropin in Y-1 cells. The possibility that the lipopolysaccharide effect is one on membrane conformation is discussed.

Adenylyl Cyclases↗
PubMed1979

Angiotensin-induced steroidogenesis in rabbit adrenal: effects of pH and calcium.

The effect of variations in pH and Ca2+ on angiotensin II (A-II)-induced steroidogenesis was tested on isolated adrenal glomerulosa cell suspensions. The results show that a reduction in pH from 7.4 to 6.5 produces both a shift to the left of the A-II dose-response curve as well as an increase in maximum steroid production. In contrast, removal of Ca2+ from the incubation medium virtually abolished steroidogenesis to A-II (5 X 10(-9)M(, KCl(10mM) and ACTH (250 microU/ml). The Ca2+ antagonist D-600, however, was less effective than simple removal of Ca2+ as 10(-4) M was required to block the steroidogenic response to these same agonists. The results indicate that the response characteristics of this system to A-II resemble most closely those seen with isolated arterial smooth muscle - especially rabbit aortic strips.

Adrenal Cortex↗
PubMed1975

Dependence of gonadotropin-induced steroidogenesis upon RNA and protein synthesis in the interstitial cells of the rat testis.

The effects of inhibitors of RNA and protein synthesis upon gonadotropic stimulation of testosterone and cyclic AMP production by the Leydig cellwere investigated in vitro with enzyme-dispersed interstitial cells of the rat testis. The testosterone response to human chorionic gonadotropin was abolished by cycloheximide and puromycin, and was markedly reduced by actinomycin D and cordycepin. During 3-h time studies, cycloheximide caused complete inhibition of subsequent steroid production when added at times up to 90 min after the commencement of incubation with human chorionic gonadotropin. Actinomycin D did not completely abolish the testosterone response when added at zero time, and became progressively less effective when added at later times during the incubation period. The stimulation of steroidogenesis by dibutyryl cyclic AMP was also completely abolished by cycloheximide and puromycin, and was significantly reduced by acinomycin D and cordycepin. By contrast with the marked inhibition of steroid production by cycloheximide and actinomycin D, the formation of cyclic AMP during human chorionic gonadotropin stimulation was relatively unaffected by either inhibitor. These results indicate that the stimulation of testosterone production by the Leydig cell in response to gonadotropins and dibutyryl cyclic AMP is dependent upon the synthesis of new RNA and protein moleucles. Thus, effects of gonadotropin and cyclic AMP upon both transcriptional and translational processes appear to be essential intermediate steps in the activation of testicular steroidogenesis. The rapid and complete abolition of subsequent steroid synthesis following addition of cycloheximide or puromycin to human chorionic gonadotropin-stimulated interstitial cells suggests that a relatively labile protein is formed during gonadotropin action.

Animals↗
PubMed1978

Adenosine 3':5'-cyclic monophosphate production and steroidogenesis by isolated rat adrenal glomerulosa cells. Effects of angiotensin II and [Sar 1,Ala 8]angiotensin II.

Angiotensin II effects on cyclic AMP production and steroid output were studied in a sensitive preparation of isolated rat adrenal glomerulosa cells. With increasing concentrations of angiotensin II logarithmic dose-response curves for aldosterone and cyclic AMP production were similar. The minimum effective dose (0.2nm) for stimulation of aldosterone production also significantly (P<0.001) increased cyclic AMP output. For both aldosterone and cyclic AMP production, the peptide hormone concentration eliciting maximal response (0.2mum) and the ED(50) (median effective dose) values (1nm) were the same; this is consistent with cyclic AMP acting as an intracellular mediator for angiotensin II-stimulated aldosterone production by glomerulosa cells. The angiotensin II antagonist [Sar(1),Ala(8)]angiotensin II inhibited angiotensin II-stimulated corticosterone and aldosterone production in these cells. An equimolar concentration of antagonist halved the response to 20nm-angiotensin II, and complete inhibition was observed with 0.2mum-antagonist. In contrast, [Sar(1),Ala(8)]angiotensin II had no effect on maximally stimulated steroidogenesis induced by serotonin and a raised extracellular K(+) concentration. Increasing concentrations of [Sar(1),Ala(8)]angiotensin II alone decreased corticosterone and aldosterone outputs significantly (P<0.05) at concentrations of 20nm and 2nm of antagonist respectively. A significant (P<0.001) decrease in cyclic AMP production occurred with 2mum antagonist and this was comparable with the decrease in aldosterone production. It is concluded that [Sar(1),Ala(8)]angiotensin II can independently affect glomerulosa-cell steroidogenesis, possibly by modulating adenylate cyclase activity.

Adrenal Glands↗
PubMed1977

Intermediate role of adenosine 3':5'-cyclic monophosphate and protein kinase during gonadotropin-induced steroidogenesis in testicular interstitial cells.

Discrepancies between adenosine 3':5'-cyclic monophosphate (cAMP) and steroid production have been frequently observed in isolated target cells stimulated by low concentrations of trophic hormone. This dissociation is particularly marked in the interstitial cells of the testis, where testosterone production is elicited by gonadotropin concentrations in the picomolar range. Because of these observations, and a disparity between steroidogenesis and protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37) activation in Leydig cells, the role of cAMP as a mediator of the acute steroidogenic response has been questioned. This problem has been further analyzed by assay of free and occupied cAMP-binding sites of the regulatory subunit of protein kinase in basal and hormone-stimulated cells. Free sites were measured by a [(3)H]-cAMP-binding assay, and occupied sites were measured by radioimmunoassay of endogenous cAMP eluted from receptor protein. After stimulation of purified Leydig cells with 0.1-10 pM human chorionic gonadotropin, a dose-dependent decrease in available [(3)H]cAMP-binding sites was observed, with no change in binding affinity. The reduction in cAMP-binding sites was equivalent to the increase in occupancy of cAMP receptors by endogenous nucleotide formed during gonadotropin action. Fractional occupancy of cAMP receptors rose progressively from basal values of 0.2-0.40 to full saturation as intracellular cAMP rose 10- to 30-fold during hormone stimulation. The testosterone dose-response curve was coincident with the initial part of the cAMP-receptor occupancy curve. These changes in endogenous cAMP binding to the regulatory subunit were accompanied by a significant increase in protein kinase activity in gonadotropin-stimulated Leydig cells. These observations provide direct evidence for the role of cAMP and protein kinase during hormonal activation of steroidogenesis in the Leydig cell by low concentrations of gonadotropin.

Animals↗
PubMed1978

Gonadotropin binding and stimulation of steroidogenesis in Leydig tumor cells.

Testicular tumors are generally characterized by a loss of responsiveness to gonadotropins. The M5480 Leydig cell tumor is unusual, if not unique, in that it responds to human choriogonadotropin and to lutropin via increased steroidogenesis. This report describes the identification of two variants of the original M5480 tumor that have altered steroid output both in the basal state and in response to human choriogonadotropin. One of the tumors produces mainly progesterone, which is stimulated by the choriogonadotropin; the other tumor produces about equal amounts of progesterone and testosterone, and the secretion of both is stimulated by the choriogonadotropin. The dissociation constant describing the interaction between Leydig tumor cells and (125)I-labeled human choriogonadotropin is between 3 and 5x10(-11) M. This agrees with values reported for normal Leydig cells, although the tumor cells appear to have fewer receptors. The differences noted in the two tumors and normal Leydig cells may have arisen from alterations in gene regulation, or in mutations, involving one or more enzymes in the pathway in which progesterone is converted to testosterone. Under the experimental conditions used, all the tumors studied (seven generations) responded to the choriogonadotropin both in binding and in the resultant stimulation of steroidogenesis. This property, together with the characteristic that a homogeneous cell population can be obtained without enzymatic treatment, should qualify the M5480 Leydig cell tumor(s) as a model system for further studies on the mechanism of action of gonadotropin, on hormone receptors, and on hormonally responsive tumors.

Animals↗
PubMedDate not supplied

Andrenogonadal interactions in nicotine-induced alteration of steroidogenesis in male rat.

Chronic nicotine administration in larger doses inhibits steroidogenesis in testis. This inhibition is possibly secondary to increased adrenomedullary norepinephrine activity, since the anti-steroidogenic effect of nicotine can be prevented by alpha-adrenergic blocker like phentolamine. In vitro incubation of testicular slices with nicotine failed to elicit any appreciable effect on delta 5-3 beta-hydroxysteroid dehydrogenase activity indicating lack of direct action of nicotine on testicular steroidogenesis.

3-Hydroxysteroid Dehydrogenases↗
PubMed1975

Effect of steroidogenesis on ascorbic acid content and uptake in isolated adrenal cells.

Isolated adrenal cell preparation was used to investigate the relationship between ascorbic acid and steroidogenesis by two methods: (1) in vivo incorporation of exogenous [1-14C]ascorbic acid into endogenous ascorbic acid of adrenal by intraperitoneal injection of labeled ascorbic acid into rats and studying the depletion of labeled ascorbic acid under a variety of experimental conditions; and (2) study of the uptake of [14C]ascorbic acid by IAC in response to steroidogenic stimuli and various steroids. These studies demonstrate that: 1. IAC preparation by the trypsin digestion method results in almost total depletion of ascorbic acid from adrenal cells, i.e., ascorbic acid content of the cell preparation was less than 1% of the original ascorbic acid in quartered adrenal gland. 2. In spite of such a severe depletion of ascorbic acid, steroidogenesis in response to ACTH and dibutyryl cyclic AMP (dcAMP) is quite pronounced. 3. ACTH and dcAMP affect depletion of endogenously labeled ascorbic acid in IAC by a process that is both concentration- and time-dependent, but is independent of steroidogenic processes. 4. ACTH and dcAMP both inhibit the uptake of exogenous [1-14C]ascorbic acid, which is time-dependent but independent of the steroidogenic phenomenon. 5. The uptake of [14C]ascorbic acid by IAC is independent of extra-to-intracellular gradient of glucocorticoids or mineralocorticoids.

Adrenal Glands↗