Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UNIPROT:P01189 (beta-endorphin)
21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of late onset 3 beta-hydroxy steroid dehydrogenase (3 beta-HSD) type of congenital adrenal hyperplasia was studied in 58 north Indian hirsute women. The age range of these patients was 15 to 42 yr. Fifty two per cent of these patients had body mass index > 25. Basal serum testosterone, luteinizing hormone, follicle stimulating hormone, dehydroepiandrosterone sulphate (DHEAS), and 17 hydroxy progesterone (17 OHP) were estimated. All the patients underwent adrenocorticotropin (ACTH) stimulation test after an overnight dexamethasone suppression for the estimation of DHEAS, 17 OHP, and 17 hydroxy pregnenolone (delta 5-17p). Five (8.6%) hirsute women showed an exaggerated 17 OHP response to ACTH indicating 21-hydroxylase deficiency. Eight (13.8%) hirsute women had elevated basal DHEAS and ACTH-stimulated DHEAS as well as delta 5-17P responses indicative of 3 beta-HSD deficiency. In one patient hirsutism was the presenting manifestation of tumoural hyperandrogenism. Our findings indicate the presence of both 21-hydroxylase and 3 beta-HSD deficiency in north Indian hirsute women, with, 3 beta-HSD deficiency being the major cause of hirsutism in this population.
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PMID:Late onset adrenal hyperplasia due to 3 beta-hydroxy-delta 5-steroid dehydrogenase deficiency in north Indian hirsute women. 902 32

In this review we analyze the morphologic changes, hypothalamic-pituitary-adrenal (HPA) axis functions, glucocorticoid (GC) receptors, and steroidogenic enzyme activities in both animals and humans during aging. In rodent studies, older animals tend to show: 1) hypertrophy of adrenal zona fasciculata (ZF) cells; 2) neuronal loss in the hypothalamic area; 3) loss of GC receptors in the hippocampus; 4) raised circulating adrenocorticotropic hormone (ACTH) and GC levels, and increased release of corticotropin-releasing hormone from the hypothalamus; 5) reduced suppression of endogenous GC secretion after administration of dexamethasone; 6) decreased attenuation of response to chronic stress; and 7) increased activity of P450scc and 21-hydroxylase. According to the GC cascade hypothesis, stress and GCs facilitate the aging process in rats. Stress induces downregulation of GC receptors in the hippocampus, then impairs GC feedback on stress-induced HPA axis activation. Finally, an increase in the basal level of corticosterone and extended GC secretion following stress occurs. Because activation of the hippocampus decreases HPA axis function, the unrestrained elevation of GC concentration and the reduction in the level of GC receptors in the hippocampus may gradually weaken the feedback mechanisms and halt the response to stress. In humans, there are conflicting reports of HPA axis function during aging, so it is difficult to make a final conclusion regarding the relationship between aging and HPA axis function.
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PMID:Glucocorticoids and aging. 934 78

The acute effects of thyroid hormones on glucocorticoid secretion were studied. Venous blood samples were collected from male rats after they received intravenous 3,5,3'-triiodothyronine (T3) or thyroxine (T4). Zona fasciculata-reticularis (ZFR) cells were treated with adrenocorticotropic hormone (ACTH), T3, T4, ACTH plus T3, or ACTH plus T4 at 37 degrees C for 2 h. Corticosterone concentrations in plasma and cell media, and also adenosine 3',5'-cyclic monophosphate (cAMP) production in ZFR cells in the presence of 3-isobutyl-1-methylxanthine, were determined. The effects of thyroid hormones on the activities of steroidogenic enzymes of ZFR cells were measured by the amounts of intermediate steroidal products separated by thin-layer chromatography. Administration of T3 and T4 suppressed the basal and the ACTH-stimulated levels of plasma corticosterone. In ZFR cells, both thyroid hormones inhibited ACTH-stimulated corticosterone secretion, but the basal corticosterone was inhibited only with T3 > 10(-10) M or T4 > 10(-8) M. Likewise, T3 or T4 at 10(-7) M inhibited the basal- and ACTH-stimulated levels of intracellular cAMP. Physiological doses of T3 and T4 decreased the activities of 3 beta-hydroxysteroid dehydrogenase, 21-hydroxylase, and 11 beta-hydroxylase. These results suggest that thyroid hormones counteract ACTH in adrenal steroidogenesis through their inhibition of cAMP production in ZFR cells.
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PMID:Acute effects of thyroid hormones on the production of adrenal cAMP and corticosterone in male rats. 948 53

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a common autosomal-recessive disorder. To ascertain carrier status, adrenocorticotropin (ACTH) stimulation tests are often used. To determine the sensitivity of ACTH stimulation to detect heterozygotes and to correlate stimulated 17-hydroxyprogesterone responses with molecular genotype, we compared molecular genetic analysis of the 21-hydroxylase (CYP21) gene with 17-hydroxyprogesterone responses at 30 min in 51 individuals. Molecular genotype analysis and ACTH stimulation tests were performed in healthy volunteers (n = 20) and relatives of patients with congenital adrenal hyperplasia (n = 31). Polymerase chain reaction (PCR) amplification, single-strand conformational polymorphism (SSCP) analysis, allele-specific oligonucleotide hybridization (ASOH) analysis, and restriction fragment length polymorphism (RFLP) analysis were utilized to screen for 14 CYP21 mutations which account for >90% of the mutations associated with 21-hydroxylase deficiency. Molecular genotype analysis classified 28 individuals as heterozygotic carriers and 23 individuals as normal for all mutations tested. As a group, the heterozygotes had significantly greater stimulated 17-hydroxyprogesterone responses at 10 and 30 min (P < 0.0005). However, on an individual basis, 14/28 (50%) genotyped heterozygotic carriers had stimulated 17-hydroxyprogesterone concentrations, 17-hydroxyprogesterone/cortisol ratios, and 17-hydroxyprogesterone incremental elevations indistinguishable from the genotyped normal individuals. Thus, a normal 17-hydroxyprogesterone response to ACTH stimulation testing does not exclude carrier status for 21-hydroxylase deficiency. Molecular genotype analysis is a more reliable method to determine 21-hydroxylase heterozygotes.
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PMID:Identification of heterozygotic carriers of 21-hydroxylase deficiency: sensitivity of ACTH stimulation tests. 954 98

Stress susceptibility in pigs is inherited by a single recessive gene (Hal(n)), and homozygous individuals can be identified by exposure to halothane anesthesia. Previous studies have shown that in stress-susceptible pigs, exposure to a high ambient temperature resulted in a twofold increase in corticotropin (ACTH) and lower plasma cortisol. To determine whether there is a fundamental difference in adrenocortical function between halothane-sensitive (HAL-S) and halothane-resistant (HAL-R) pigs, independent of other factors influencing the hypothalamic-pituitary-adrenal (HPA) axis, we compared cortisol responses to ACTH and 8-bromo-cyclic AMP (8-Br-cAMP) in HAL-S and HAL-R pig adrenocortical cells in vitro. We also determined directly the accumulation of four different mRNAs encoding cholesterol side-chain cleavage cytochrome P450 (P450(scc)), 17alpha-hydroxylase cytochrome P450 (P450(17alpha)), 21-hydroxylase cytochrome P450 (P450(c21)) and 11beta-hydroxylase cytochrome P450 (P450(11beta)) in HAL-S pig adrenal cells and compared them to HAL-R pigs. A time- and dose-dependent increase in medium content of cortisol and cAMP was observed after ACTH treatment. 8-Br-cAMP also caused a time- and dose-dependent increase in cortisol production in the medium. Addition of ACTH or 8-Br-cAMP to HAL-S and HAL-R male Lanyu small-ear miniature pig adrenocortical cells increased cortisol production in a dose- and time-related manner. However, cells isolated from HAL-S pigs had a lower cortisol production in response to ACTH or 8-Br-cAMP compared to those from HAL-R pigs. Treatment of cultured cells with 8-Br-cAMP (0.5 mM) for 18 h resulted in a significant increase in P450(scc), P450(17alpha), P450(c21), and P450(11beta) mRNA levels. In the absence of 8-Br-cAMP, the four genes were expressed constitutively in both HAL-S and HAL-R pig adrenal cells. Densitometric scanning of the autoradiograph indicated that the relative amounts of P450(scc) and P450(17(alpha)) mRNAs in HAL-S pig adrenal cells were between 48% and 53% of those detected in HAL-R pig adrenal cells (P < 0.05). No difference in the amounts of P450(c21) and P450(11beta) was seen in HAL-S and HAL-R pig adrenal cells. Addition of 8-Br-cAMP (0.5 mM) resulted in a uniform increase in the levels of all four P450 mRNAs in both HAL-S and HAL-R pig adrenal cells. However, the amounts of P450(scc) mRNA in HAL-S pig adrenal cells were 67% (P < 0.05) of those measured in HAL-R pig adrenal cells, whereas the amounts of P450(17alpha ), P450(c21), and P450(11beta) mRNAs were similar in these cells. Our data suggest an HPA axis defect in HAL-S pigs at the adrenal level. This defect appears to be at the level of P450scc gene expression, which could be partially related to reduced cortisol production by ACTH stimulation.
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PMID:Expression of steroidogenic enzyme messenger ribonucleic acid and cortisol production in adrenocortical cells isolated from halothane-sensitive and halothane-resistant pigs. 1090 55

The adrenal production of the delta 5-androgens, dehydroepiandrosterone (DHEA) and its sulfate ester dehydroepiandrosterone sulfate (DHEAS), declines linearly with aging. The evidence that DHEA or DHEAS administration may alleviate some of the problems related to aging has opened new perspectives for clinical research. The present study aims to investigate the effects of a 6-month DHEA supplementation in early and late postmenopausal women, with normal or overweight body mass index (BMI), on the level of circulating steroids, sex hormone binding globulin (SHBG), beta-endorphin and gonadotropins, and on the adrenal gland response to dexamethasone suppression and adrenocorticotropic hormone (ACTH) stimulation. Early postmenopausal women (50-55 years) both normal weight (BMI 20-24, n = 9) and overweight (BMI 26-30, n = 9) and late postmenopausal women (60-65 years) both of normal weight and overweight, were treated with oral DHEA (50 mg/day). Circulating DHEA, DHEAS, 17-OH pregnenolone, progesterone, 17-OH progesterone, allopregnenolone, androstenedione, testosterone, dihydrotestosterone, estrone, estradiol, SHBG, cortisol, luteinizing hormone, follicle stimulating hormone and beta-endorphin levels were evaluated monthly and a Kupperman score was performed. The product/precursor ratios of adrenal steroid levels were used to assess the relative activities of the adrenal cortex enzymes. Before and after 3 and 6 months of therapy, each women underwent an ACTH stimulating test (10 micrograms i.v. in bolus) after dexamethasone administration (0.5 mg p.o.) to evaluate the response of cortisol, DHEA, DHEAS, androstenedione, 17-OH pregnenolone, allopregnanolone, progesterone and 17-OH progesterone. The between-group differences observed before treatment disappeared during DHEA administration. Levels of 17-OH pregnenolone remained constant during the 6 months. Levels of DHEA, DHEAS, androstenedione, testosterone and dihydrotestosterone increased progressively from the first month of treatment. Levels of estradiol and estrone significantly increased after the first/second month of treatment. Levels of SHBG significantly decreased from the second month of treatment only in overweight late postmenopausal women, while the other groups showed constant levels. Progesterone levels remained constant in all groups, while 17-OH progesterone levels showed a slight but significant increase in all groups. Allopregnanolone and plasma beta-endorphin levels increased progressively and significantly in the four groups, reaching values three times higher than baseline. Levels of cortisol and gonadotropins progressively decreased in all groups. The product/precursor ratios of adrenal steroid levels at the sixth month were used to assess the relative activities of the adrenal cortex enzymes and were compared to those found before therapy. The 17,20-desmolase, sulfatase and/or sulfotransferase, 17,20-lyase and 5 alpha-reductase activities significantly increased, while the 3 beta-hydroxysteroid-oxidoreductase activity did not vary. On the contrary, the 11-hydroxylase and/or 21-hydroxylase activities showed a significant decrease after 6 months of treatment. In basal conditions, dexamethasone significantly suppressed all the adrenal steroids and this suppression was greater after 3 and 6 months of treatment for DHEA, DHEAS and allopregnanolone, while it remained unchanged for other steroids. Before treatment, ACTH stimulus induced a significant response in all parameters; after the treatment, it prompted a greater response in delta 5- and delta 4-androgens, progesterone and 17-OH progesterone, while cortisol responded less in both younger and older normal-weight women. The endometrial thickness did not show significant modifications in any of the groups of postmenopausal women during the 6 months of treatment. Treatment with DHEA was associated with a progressive improvement of the Kupperman score in all groups, with major effects on the vasomotor symptoms in
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PMID:Six-month oral dehydroepiandrosterone supplementation in early and late postmenopause. 1110 74

A 60-year-old woman presented with a history of palpitations, headaches and severe hypertension, which was resistant to hypotensive agents. She had a 2-year history of obesity and a moon face. Her plasma adrenocorticotropic hormone level was below the limits of detection and did not respond to corticotropin-releasing hormone. Urinary-free cortisol was elevated and the circadian rhythm of serum cortisol level had completely disappeared. Imaging analysis demonstrated a unilaterally functioning mass in the left adrenal gland. Serum cortisol level in the left adrenal vein was elevated. The resected adrenal mass measured 4 x 3.5 x 2.5 cm, and ranged from yellow to tan in color. The adrenal cortex adjacent to the nodule did not demonstrate cortical atrophy. The mass was well circumscribed but not encapsulated, and consisted of multiple cortical nodules. These nodules were composed predominantly of clear cortical cells, and partly of compact cortical cells. Immunoreactivity of steroidogenic enzymes including cholesterol side-chain-cleavage P450, 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase cytochrome P450, 11beta-hydroxylase cytochrome P450 and 17alpha-hydroxylase cytochrome P450 was marked in cortical nodules, but minimal in non-nodular cortex. Ultrastructural examination of nodular cortical cells also demonstrated well-developed mitochondria and smooth endoplasmic reticulum, consistent with elevated steroidogenesis in these cells.
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PMID:Adrenocorticotropin-independent unilateral adrenocortical hyperplasia with Cushing's syndrome: Immunohistochemical studies of steroidogenic enzymes, ultrastructural examination and a review of the literature. 1116 51

Congenital adrenal hyperplasia describes a group of inherited autosomal recessive disorders characterized by an enzymatic defect in cortisol biosynthesis, compensatory increases in corticotropin secretion, and adrenocortical hyperplasia. 21-Hydroxylase deficiency is responsible for more than 95% of cases and is one of the most common known autosomal recessive disorders. The classic or severe type presents in the newborn period or early childhood with virilization and adrenal insufficiency, with or without salt loss; the mild or nonclassic form presents in late childhood or early adulthood with mild hyperandrogenism and is an important cause of masculinization and infertility in women. This wide range of phenotypic expression is mostly explained by genetic variation, although genotype-phenotype discrepancies have been described. Reproductive, metabolic, and other comorbid conditions, including risk for tumors, are currently under investigation in both forms of the disease. A high proportion of patients with adrenal incidentalomas may be homozygous or heterozygous for 21-hydroxylase deficiency. Women with congenital adrenal hyperplasia often develop the polycystic ovary syndrome. Ectopic adrenal rest tissue is often found in the testes of men with congenital adrenal hyperplasia; characteristic clinical and radiologic findings help differentiate this tissue from other tumors. Levels of corticotropin-releasing hormone are elevated in patients with depression and anxiety and are expected to be elevated in patients with congenital adrenal hyperplasia; it is unknown whether patients with 21-hydroxylase deficiency have an increased incidence of these psychiatric disorders. Abnormalities in both the structure and function of the adrenal medulla have been shown in patients with classic congenital adrenal hyperplasia, and the degree of adrenomedullary impairment may be a biomarker of disease severity. The 21-hydroxylase-deficient mouse has provided a useful model with which to examine disease mechanisms and test new therapeutic interventions in classic disease, including gene therapy. Treatment of this condition is intended to reduce excessive corticotropin secretion and replace both glucocorticoids and mineralocorticoids. However, clinical management is often complicated by inadequately treated hyperandrogenism, iatrogenic hypercortisolism, or both. New treatment approaches currently under investigation include combination therapy to block androgen action and inhibit estrogen production, and bilateral adrenalectomy in the most severely affected patients. Other approaches, which are in a preclinical stage of investigation, include treatment with a corticotropin-releasing hormone antagonist and gene therapy.
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PMID:NIH conference. Future directions in the study and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. 1184 30

The aim of the study was to compare the response between the standard and low dose adrenocorticotropin (ACTH) test for patients with congenital adrenal hyperplasia (CAH). The authors employed a 2-by-2 crossover design and enrolled 16 patients, 14 girls and 2 boys, aged between 1.4 months and 15 years. Steroid treatment was stopped 24 hours before each test was conducted. The standard ACTH (250 microg) test was performed followed by the low dose test (1 microg) in eight patients; the other eight underwent the low dose ACTH test first followed by the standard one. The cortisol and 17-hydroxyprogesterone (17-OHP) levels in each patient varied unpredictably between the two tests. The cortisol responses to the low dose ACTH at 30 and 60 minutes were lower than at time zero; in contrast to the 60-minute peak cortisol response to the standard dose. The serum 17-OHP in all specimens was more than 10,000 ng/dl (300 nmol/L), with the peak response at 60 minutes in both groups. Both the low dose and standard dose ACTH test indicated adrenal insufficiency and the high 17-OHP levels were diagnostic of 21- hydroxylase (21-OH) deficiency. If the low dose ACTH test becomes the "standard" ACTH test, the diagnosis of 21-OH deficiency would probably not be missed.
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PMID:Adrenocorticotropin stimulation test in congenital adrenal hyperplasia: comparison between standard and low dose test. 1294 58

Polycystic ovary syndrome (PCOS) affects about 4 to 6% of women of reproductive age and accounts for at least 75% of hyperandrogenic patients. PCOS is diagnosed by the presence of oligo-ovulation and hyperandrogenism after the exclusion of related disorders, such as 21-hydroxylase-deficient nonclassic adrenal hyperplasia (NCAH). In turn, NCAH is a homozygous recessive disorder, diagnosed by a corticotropin-stimulated 17-hydroxyprogesterone (17-HP) level greater than10 ng/mL (30.3 nmol/L) and confirmed by genotyping of the CYP21 gene. The prevalence of NCAH is approximately 50 times less than that of PCOS, affecting between 1 and 10% of hyperandrogenic women, depending on ethnicity. However, it is generally difficult to distinguish NCAH from PCOS solely on clinical grounds, as both demonstrate varying degrees of hyperandrogenism and ovulatory dysfunction. Most PCOS patients have insulin resistance, in contrast to those with NCAH. Likewise, polycystic ovaries are observed in up to 40% of NCAH patients. Both disorders have a strong familial component. The only method that allows the separation of NCAH from PCOS patients is the measurement of 17-HP levels. In conclusion, PCOS and NCAH have differences in prevalence and pathophysiology. However, because the disorders have significant clinical and hormonal similarities, the measurement of 17-HP, preferably basally as a screening method, should be incorporated into the evaluation of all hyperandrogenic patients.
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PMID:21-hydroxylase-deficient nonclassic adrenal hyperplasia: the great pretender. 1459 52


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