Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
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Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: EC:1.1.1.3 (
HSD
)
3,464
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
An increase in fetal adrenal cortisol output signals the onset of parturition in many animal species but, in the fetal horse, plasma concentrations of cortisol remain low for much of late pregnancy, with a rise occurring only very close to the time of birth (term 320-360 days). Immunohistochemistry was used to determine the localisation and changes in distribution of key steroidogenic enzymes for cortisol production; P450scc, P450C17 and 3 beta-hydroxysteroid dehydrogenase (3 beta
HSD
) in adrenal tissue from fetal and newborn horses and these findings were correlated with the appearance of immunoreactive (IR)-phenylethanolamine-N-methyl-transferase (PNMT), a cortisol-dependent enzyme. Five micron sections of adrenal tissue from fetuses at Day 100-156 (n = 5), Day 244-295 (n = 8), greater than Day 300 (n = 4) and from newborn foals (n = 6), were stained using specific antibodies and the avidin-biotin-peroxidase technique. All 3 steroidogenic enzymes were present by Day 150, but in less than 20% of the cortical cells. By late gestation the steroidogenic enzymes were present in approximately 30% of the cells, but the distribution varied.
P450SCC
and P450C17 predominated in cortical cells proximal to the medulla; 3 beta
HSD
was present throughout the cortex, but more in the zona fasciculata. In foals after birth, IR-3 beta
HSD
and IR-
P450SCC
had increased substantially throughout the adrenal cortex, and IR-P450C17 was present in most cells of the presumptive zonae fasciculata and reticularis. IR-PMNT was localised to nuclei of scattered medullary cells at the medullary-cortical interface by Day 150.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Immunohistochemical localisation of steroidogenic enzymes and phenylethanolamine-N-methyl-transferase (PNMT) in the adrenal gland of the fetal and newborn foal. 760 48
The physiological importance of adrenal 21-hydroxylase cytochrome P450 (CYP21) expression is clearly demonstrated by 21-hydroxylase deficiency, which results in adrenal hyperplasia and over-production of C19 steroids, leading to virilization. The mechanisms regulating normal expression of this key enzyme in human adrenocortical cells are ill defined. Herein we examine the role of the calcium, protein kinase C, and protein kinase A signaling pathways in the expression of CYP21 messenger ribonucleic acid (mRNA) using the H295R human adrenocortical cell model. Forskolin (10 mumol/L) treatment caused a progressive increase in CYP21 mRNA levels (maximum, 4-fold; P < 0.05) over 36 h of treatment, whereas angiotensin II (AII; 10 nmol/L) produced a smaller, biphasic rise (maximum, 1.8-fold at 12 h; P < 0.05). K+ (14 mmol/L) also induced a time-dependent (maximal, 1.5-fold at 12 h; P < 0.05) and dose-dependent (P < 0.05 12 mmol/L or above at 20 h) rise in CYP21 mRNA levels. The action of forskolin was reproduced by dibutyryl cAMP, confirming the involvement of cAMP in this response. The action of AII was greater than that of K+ or the calcium channel agonist BAYK8644, suggesting that AII action was not solely through the Ca2+ signaling pathway. The action of AII was reproduced and indeed exceeded by the protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA; 10 nmol/L; 5.5-fold increase; P < 0.05). The actions of forskolin alone were not significantly increased by combined treatment with AII, suggesting neither synergy nor attenuation of the effects of protein kinase A activation. This was further demonstrated at the level of mRNA and 21-hydroxylase activity by the observation that the effect of forskolin and TPA in combination did not exceed that of TPA alone. Inhibition of protein synthesis with cycloheximide blocked induction of CYP21 as well as type II 3 beta-hydroxysteroid dehydrogenase (3 beta HSDII) mRNA expression in response to AII, forskolin, and dibutyryl cAMP, but had no effect on 17 alpha-hydroxylase cytochrome P450 (CYP17) or cholesterol side-chain cleavage cytochrome P450 (
CYP11A
) mRNA. Together, these findings were remarkably similar to those of our previous studies regarding mechanisms regulating 3 beta HSDII expression and underline the existence of a subset of steroidogenic enzymes regulated positively (CYP21 and 3 beta HSDII) as opposed to negatively (CYP17 and
CYP11A
) by the protein kinase C signaling pathway. The additional finding of a small induction of CYP21 expression in response to increased Ca2+, as previously reported for CYP17, but not 3 beta HSDII, expression, also demonstrates that the mechanisms of control of CYP21 and 3 beta HSDII are not identical. This latter finding may also relate to how CYP21 as well as CYP17 expression continues in the zona reticularis after adrenarche, whereas 3 beta
HSD
expression declines.
...
PMID:Protein kinase A, protein kinase C, and Ca(2+)-regulated expression of 21-hydroxylase cytochrome P450 in H295R human adrenocortical cells. 958 61
Testosterone secretion and the expression and relative contents of steroidogenic acute regulatory (StAR) protein and steroidogenic enzymes cholesterol side-chain cleavage cytochrome P450 (
P450SCC
), 3beta-hydroxysteroid dehydrogenase/delta(5)-->delta(4)-isomerase (3 beta-HSD), and (17)alpha-hydroxylase cytochrome P450/C17-20 lyase (P450(17)alpha) were determined in testicular tissues of bulls treated with a LHRH agonist. Testis morphology and spermatogenesis were also examined. In Experiment 1, bulls (30-mo-old) received no treatment (control, n = 7) or were implanted for 10 days with the LHRH agonist deslorelin (n = 7). Bulls were castrated on Day 10 and testis tissues prepared for Western and Northern blotting. At castration, bulls implanted with deslorelin had greater plasma testosterone (5-fold) and testis content of testosterone (10-fold) compared with control bulls. Relative content (per micrograms total testis protein or RNA) of StAR protein, 3beta-
HSD
,
P450SCC
, and mRNA for P450(17)alpha in bulls treated with deslorelin ranged from 3- to 6-fold that of control bulls. In Experiment 2, bulls (20-mo-old) were left untreated (control, n = 6) or implanted with deslorelin (n = 12) for 120 days. On Day 120, bulls were castrated and right testis tissues prepared for morphology. Testis volume and weight were increased (P < 0.01) in bulls treated with deslorelin compared with control bulls. Stereological analysis revealed that this increase occurred in all compartments (seminiferous epithelium, lumen and interstitium) studied, but was significant (P < 0.01) only for the seminiferous epithelium. Absolute numbers of round spermatids per testis were increased (P < 0.05) in bulls treated with deslorelin compared with control bulls. Increased testosterone secretion in bulls treated with deslorelin was associated with increased testicular StAR protein and steroidogenic enzymes. Bulls treated long-term with deslorelin had a faster rate of testis growth and increased daily sperm production at the end of the experiment.
...
PMID:Changes in testicular steroidogenic acute regulatory (STAR) protein, steroidogenic enzymes and testicular morphology associated with increased testosterone secretion in bulls receiving the luteinizing hormone releasing hormone agonist deslorelin. 967 55
The objectives of this study were to determine whether stress attenuates the pituitary LH response to excitatory amino acids by altering expression of glutamate receptor 1 (GluR1) and N-methyl-D-aspartic acid (NMDA) receptor mRNA levels in the hypothalamus or pituitary, and assess whether stress influences testicular levels of mRNA or protein for steroidogenic enzymes. Three hours (h) of immobilization stress was associated with a greater than 7-fold increase in serum corticosterone, and a marked reduction in serum testosterone (T) concentrations. Stress did not significantly alter hypothalamic or pituitary GluR1 and NMDA receptor mRNA levels. Although transcript levels for
P450SCC
and P45017alpha mRNA in the testis were unchanged in stressed rats, western blotting of testicular fractions revealed reduced amounts of
P450SCC
and 3beta-
HSD
, but not P45017alpha. The data suggest that immobilization stress reduces T production by suppressing the translation of transcripts for
P450SCC
and 3beta-
HSD
, but the attenuated LH response of stressed animals to NMDA is not mediated by altered hypothalamic or pituitary expression of GluR1 and NMDA receptor levels.
...
PMID:Expression of mRNA and proteins for testicular steroidogenic enzymes and brain and pituitary mRNA for glutamate receptors in rats exposed to immobilization stress. 1062 2
The signal initiating ovarian theca cell (TC) differentiation is gonadotropin independent because theca precursor cells do not contain LH receptors. Previously we demonstrated that preantral follicles produce paracrine TC differentiating factors that promote androgen production by an LH-independent mechanism. This study tested the effects of two granulosa cell-produced peptides, insulin-like growth factor-I (IGF-I) and stem cell factor (SCF), on TC differentiation and androgen production. Neutralizing antibodies to either IGF-I or SCF blocked the stimulatory effects of follicle-conditioned medium on TC precursor differentiation more than 90%. The TC isolated from the ovaries of hypophysectomized immature rats by percoll gradient centrifugation were cultured (48 h) with and without SCF (0-100 ng/ml) and IGF-I (0-100 ng/ml) to test their effects on TC differentiation. Androsterone in the medium was measured by RIA. Luteinizing hormone receptor, steroidogenesis acute regulatory protein (StAR),
CYP11A
, CYP17, and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) mRNAs were measured by specific reverse transcriptase polymerase chain reaction assays. Stem cell factor or IGF-I alone did not stimulate androsterone production but in combination caused a concentration-dependent increase in androsterone levels. Maximum androsterone levels were less than those stimulated by LH (0.1 ng/ml) alone. Although IGF-I synergistically augmented LH stimulation of androsterone production, SCF did not alter LH-stimulated androsterone production in the presence or absence of IGF-I. Stem cell factor alone had no effect on LH receptor, StAR,
CYP11A
, and 3beta-
HSD
mRNA expression but decreased CYP17 mRNA levels. Insulin-like growth factor-I alone had no effect on StAR or CYP17 mRNA expression but increased LH receptor,
CYP11A
, and 3beta-
HSD
mRNA levels. In combination, SCF plus IGF-I increased the expression of all five mRNAs. These data support the conclusion that IGF-I and SCF are important regulators of TC differentiation.
...
PMID:Stem cell factor and insulin-like growth factor-I stimulate luteinizing hormone-independent differentiation of rat ovarian theca cells. 1115 46
In this study, the expression of several genes involved in cortisol synthesis in head kidneys, the site of cortisol production, and in the rainbow trout (Oncorhynchus mykiss) was examined in response to two different acute stressors and an acute ACTH treatment. mRNAs levels of the "steroidogenic acute regulatory" (StAR) sterol transport protein, which transports cholesterol to the inner mitochondrial membrane as well as cytochrome P450 cholesterol side chain cleavage (
P450(SCC)
) were determined in head kidney (containing the interrenal tissue). In one experiment, we also quantified 3-beta-hydroxysteroid dehydrogenase (3B-HSD) and cytochrome P450(11beta) (11B-H) mRNAs. The presence of these four transcripts in the head kidney was confirmed by Northern blot analysis. For each stress condition, mRNA levels were quantified by quantitative or real-time RT-PCR. The results of these two methods were highly correlated. An acute stress induced by capture, short confinement (2min), and anesthesia (3min) resulted in significant elevation of plasma cortisol (30-fold higher than controls) and an increase in levels of StAR and
P450(SCC)
mRNAs 3h post-stress. When fish were submitted to an acute stress caused by 5min of chase with a net in a tank, plasma cortisol reached a peak within 1h, but after 3h, levels were only 5-fold higher in stressed trout than in controls and no variations in the expression of StAR,
P450(SCC)
, 3B-
HSD
, and 11B-H were observed whatever the time post-stress. One hour after acute ACTH stimulation (5IU/kg), plasma cortisol level was 4-fold higher than in control trout and no changes in StAR and
P450(SCC)
mRNAs levels were detected. The data suggest that the high levels of cortisol after stress need an activation of genes involved in cortisol synthesis, but lower levels do not. Futhermore, under these three test conditions, we always found a strong positive correlation between mRNA levels of StAR and
P450(SCC)
, in contrast to what has been described in mammals. Consequently, the absence of transcription activation with low increase in cortisol levels suggests that other levels of regulation, particularly activation of pre-existing proteins, govern cortisol production.
...
PMID:Relationship between changes in mRNAs of the genes encoding steroidogenic acute regulatory protein and P450 cholesterol side chain cleavage in head kidney and plasma levels of cortisol in response to different kinds of acute stress in the rainbow trout (Oncorhynchus mykiss). 1464 46
Follicular development and differentiation are closely associated with increasing steroidogenesis. During the present study transcript concentration of Cyp19, Cyp11A1, and 3beta-hydroxysteroid dehydrogenase delta (3beta-HSD) encoding the steroidogenic enzymes P450(arom),
P450(SCC)
, and 3beta-
HSD
were determined by real-time PCR in bovine granulosa cells (GC) as potential markers for follicular differentiation. Ovaries were collected from a local abattoir (experiment 1) and from synchronized animals at day 4 of estrus cycle (experiment 2). To study effects of luteinization, steroidogenic transcripts were also quantified in corpora lutea (CL) 4 and 20 days after fertilization. In most follicles, all three steroidogenic transcripts were detected, however, at very different concentration. Expression of 3beta-
HSD
and Cyp11A1 was highly significantly co-regulated and showed a significant correlation with follicular size. Contrary, Cyp19 expression was extremely variable even in follicles of similar size. Cyp19 transcripts were derived predominantly from promoter P2 and less abundant from promoters P1.1 and P1.5. After luteinization, the concentration of 3beta-
HSD
and Cyp11A1 transcripts increased (75-fold and fivefold, respectively) whereas the Cyp19 transcript level dropped (160-fold). Residual Cyp19 transcripts in CL were almost exclusively derived from P1.1. The data indicate that Cyp19 expression in GC is predominantly regulated by P2 and to a minor extend by P1.1, whereas P1.1 is almost exclusively responsible for residual Cyp19 expression in CL. Correlation analyses suggest that the expression of 3beta-
HSD
and Cyp11A1 primarily depend on the size of follicles whereas the concentration of P2 derived Cyp19 transcripts in GC is a marker for follicular differentiation towards selection and dominance.
...
PMID:Expression of the bovine aromatase cytochrome P450 gene (Cyp19) is primarily regulated by promoter 2 in bovine follicles and by promoter 1.1 in corpora lutea. 1499 31
Gestagens and oestrogens are important regulators of pregnancy and parturition. The aim of the present study was the comparative quantification of steroidogenic transcripts in placenta and corpus luteum of cattle and sheep during pregnancy and post partum. Cyp19 transcript variants, derived from different promoters, as well as transcripts of Hsd3b, Cyp11A1, and Cyp17, encoding the steroidogenic enzymes P450arom, 3beta-
HSD
,
P450SCC
, and P450C17, respectively, were quantified by newly developed real-time PCR assays. All steroidogenic transcripts were detected in ovine and bovine corpus luteum and placenta during pregnancy, however at a very different concentration. In both species Cyp11A1 and especially Hsd3b transcripts predominated in corpus luteum, outnumbering transcripts of Cyp17 and Cyp19 by more than two and three orders of magnitude, respectively. Cyp19 transcript were found at high concentration in the placenta and at a very low concentration in corpus luteum. Cyp17 transcripts had a relatively low concentration in both, placenta and corpus luteum, however showed a peak of expression in the ovine and bovine term placenta. Tissue- and species-specific Cyp19 transcripts derived from different promoters were detected. In order to map all promoters, the bovine Cyp19 locus was reconstructed by in silico analysis. In the placenta, transcripts were primarily derived from the proximal promoter P1.5 in sheep, but from the distally located P1.1 in cattle. Corpora lutea of both species predominantly expressed P1.1 derived transcripts. Contrary to the bovine, the sheep corpus luteum also showed considerable P1.5 derived expression. This demonstrates that cattle and sheep use different promoters to direct Cyp19 expression during pregnancy.
...
PMID:Cattle and sheep use different promoters to direct the expression of the aromatase cytochrome P450 encoding gene, Cyp19, during pregnancy. 1521 30
Mycotoxins are contaminants of animal feed that can impair fertility and cause abnormal fetal development in farm animals. The aim of the present study was to investigate the influence of Fusarium-toxin contaminated feed on cumulus morphology and maturation of pig oocytes. Naturally with the Fusarium-toxins deoxynivalenol (DON) and zearalenone (ZON) contaminated wheat was included in feed for gilts at increasing proportions which resulted in increasing dietary concentrations of both toxins (in mgtoxin/kg feed: Group 1 (control), 0.21 and 0.004; Group 2, 3.07 and 0.088; Group 3, 6.1 and 0.235; Group 4, 9.57 and 0.358, for DON and ZON, respectively). Oocytes were recovered from gilt ovaries by follicle aspiration after ovario-hysterectomy. Granulosa cells were analyzed for the expression of the
P450(SCC)
and 3beta-
HSD
mRNA by RT-PCR and additionally for
P450(SCC)
protein by Western blotting. Neither the expression of the
P450(SCC)
nor of the 3beta-
HSD
mRNA or the abundance of the
P450(SCC)
protein was significantly influenced by the mycotoxin application. The distribution of different cumulus cell morphologies was not influenced by group. At the time of recovery, oocytes with compact cumuli in Groups 3 and 4 showed a reduced proportion having immature chromatin in comparison to that for Groups 1 and 2. The proportion of oocytes having degenerated meiotic chromatin was significantly higher in Group 4 than in the other groups. The proportion of oocytes reaching metaphase II in culture was significantly lower in Groups 3 and 4 than in Group 1, and tended to be lower in Group 2 than in Group 1. We conclude that oocyte quality is significantly reduced by feeding of Fusarium-toxins to gilts.
...
PMID:Influence of Fusarium-toxin contaminated feed on initial quality and meiotic competence of gilt oocytes. 1643 Oct 77
Hypoxia is affecting thousands of square kilometers of water and has caused declines in fish populations and major changes in aquatic communities worldwide. For the first time, we report that hypoxia can affect sex differentiation and sex development of zebrafish (Danio rerio), leading to a male-biased population in the F1 generation (74.4% +/- 1.7% males in the hypoxic groups versus 61.9% +/- 1.6% males in the normoxic groups, n = 5; p < 0.05, chi2 test). The increase in males was associated with downregulations of various genes controlling the synthesis of sex hormones (i.e., 3beta-
HSD
,
CYP11A
, CYP19A, and CYP19B) as well as an increase in the testosterone/estradiol ratio. The male-dominated populations caused by hypoxia will have reduced reproductive success, thereby threatening the sustainability of natural fish populations.
...
PMID:Hypoxia affects sex differentiation and development, leading to a male-dominated population in zebrafish (Danio rerio). 1671 79
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