Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q7LGC8 (HSD)
 3,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The direct effect of prolactin on rat adrenal steroidogenic enzyme activity was evaluated by measuring plasma and adrenal cytosol steroid levels and adrenal microsomal 3B-hydroxysteroid dehydrogenase/isomerase (3B-HSD), 21 hydroxylase (21-OHase) and mitochondrial 11-hydroxylase (11-OHase) after in vivo administration of purified rat prolactin (rPRL) to adult, female Sprague-Dawley rats. Animals were ovariectomized, hypophysectomized and replaced with ACTH. Two days after surgery rPRL was administered i.p. at doses of 1.0, 10.0 and 100.0 micrograms (micrograms) every 4 hours for 5 days to experimental animals. Control rats received vehicle injections. All rats were sacrificed by decapitation and blood and adrenal glands collected. The adrenals were pooled into each rPRL dose group and mitochondria, microsomes and cytosol prepared from each pool. The activities of 3B-HSD, 21-OHase and 11-OHase were measured using as substrates 14C-dehydroepiandrosterone, 14C-progesterone and 14C-deoxycorticosterone, respectively. Plasma prolactin levels rose from 9.9 +/- 2.5 ng/ml in the control animals to 166.0 +/- 37.7 ng/ml (p less than 0.001) in the 100 micrograms rPRL dose group. Plasma corticosterone levels were not statistically different in the experimental groups when compared to controls. However, adrenal weight was increased in the high dose rPRL group (34.9 +/- 0.9 mg vs 41.9 +/- 1.2 mg, p less than 0.025). Hyperprolactinemia did not influence microsomal 3B-HSD or mitochondrial 11-OHase activities but was associated with a dose dependent decrease in microsomal 21-OHase activity when compared to controls (p less than 0.001). Adrenal cytosol progesterone levels increased with increasing rPRL dose consistent with a 21-OHase block during hyperprolactinemia. These data suggest that prolactin has a direct effect on rat adrenal 21-OHase in vivo.
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PMID:New evidence for a direct effect of prolactin on rat adrenal steroidogenesis. 342 48

Cortisol 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) deficiency was observed in four patients with apparent mineralocorticoid excess. The 11 beta-HSD deficiency was demonstrated by a markedly decreased urinary tetrahydrocortisone/tetrahydrocortisol (THE/THF) ratio (less than 1 in normal children) during infusion of ACTH and administration of hydrocortisone. We propose that in these patients the 11 beta-HSD deficiency impairs the metabolism of cortisol to cortisone, resulting in a prolonged cortisol half-life, suppression of ACTH, and normal serum cortisol. The 11 beta-HSD deficiency protects the patient from adrenal insufficiency despite the low cortisol secretion; the prolonged half-life of cortisol may contribute to the hypertension and hyporeninemia observed in this disorder. Continuous intravenous hydrocortisone administration resulted in increased blood pressure and decreased serum potassium. Addition of spironolactone during continued administration of 20 mg per day of hydrocortisone resulted in a decrease in blood pressure and a rise in serum potassium. These studies suggest that an abnormality in cortisol action or metabolism results in cortisol behaving as a potent mineralocorticoid. These findings may account for this syndrome of apparent mineralocorticoid excess.
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PMID:Apparent mineralocorticoid excess causing hypertension and hypokalemia in children. 346 39

An in vitro study has been made of the steroid metabolism in the abdominal skin in two hirsute women with adrenogenital syndrome, and the concentrations of the various steroids in the skin tissue have been determined. The urinary excretion of the total 17-Ks, and particularly P-triol, was pathologically high, while of the androgens examined in the serum, primarily the levels of delta 4-dione and Test, were found to be elevated. The 21-hydroxylase deficiency meant that the plasma ACTH level was likewise extremely high in both patients. In vitro incubation studies demonstrated that in one patient (with the higher androgen overproduction) more Test. than normal was formed from the precursors (DHA, delta 5-diol, delta 4-dione), i.e. the biosynthetic pathway (17 beta-HSD, delta 5-3 beta-HSD) leading towards the androgens was enhanced in the abdominal skin. In the other patient (where the androgen production was less high as a consequence of the earlier adrenalectomy) the metabolism in the abdominal skin was not enhanced; indeed, for many metabolites the extent of the transformation did not even attain the level for normal women. The activity of Test. 5 alpha-reductase was not increased in the skin of either patient. The results on the steroid contents of the skin tissue revealed that numerous free steroids (DHA, And., delta 4-dione, delta 5-diol, Test., DHT) and C19-steroid sulphates were present in higher concentrations than in the abdominal skin of healthy women. The extents of steroid accumulation compared to the serum level in the same patient were pathologically high in the case of delta 5-diol, DHT and DHA-S in the abdominal skin of the two hirsute women with adrenogenital syndrome. This confirmed that a state of hyperandrogenism does exist in the skin of these patients.
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PMID:Metabolism and concentration of androgenic steroids in abdominal skin of hirsute women with androgenital syndrome. 623 10

A number of parallels can be drawn between the reported endocrine status of thiouracil-fed young rodents and that of aged animals, particularly with regard to the hypothalamus-pituitary-adrenal axis. Since the activity of the adrenal steroidogenic enzyme 3beta-hydroxy-delta5-steroid dehydrogenase (3beta-HSD) has been shown to be depressed in aged rats and mice, the present study was done to determine whether exposure of young mice to thiouracil had a similar effect on adrenal 3beta-HSD activity. Feeding the goitrogen thiouracil at 0.25% (w/w) of the maternal diet from conception, and keeping it 0.25% of the offsprings' diet after weaning, significantly elevated activity of 3beta-HSD per gram of adrenal gland above control levels in 4-month-old mice, perhaps to compensate for depressed adrenal mass. Daily subcutaneous injections of physiological saline (0.9%) for 4 days was sufficient to increase 3beta-HSD activity per gram of adrenal tissue in euthyroid (P less than 0.05) but not in thiouracil-fed mice. Subcutaneous administration of ACTH (2 IU daily for 4 days) significantly increased adrenal 3beta-HSD activity to comparable levels in thiouracil-fed and euthyroid animals. Thus, thiouracil enhances the activity of 3beta-HSD per gram of adrenal tissue and does not prevent response of enzyme activity to exogenous ACTH.
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PMID:Response of adrenal 3beta-hydroxy-delta5-steroid dehydrogenase to adrenocorticotropin treatment in thiouracil-fed male mice. 627 60

Acquired virilism in adult females amy be due to a number of primary disorder of the adrenal or the ovary, or both. In this review, HSD deficiency has been presented as one distinct cause. Its diagnosis as described in the report by Rosenfield and his co-workers depends upon several features. The urinary pattern of delta 5-3 beta-ol metabolites should be typical of that of congenital HSD deficiency. The excretion of pregnenetriol as compared with pregnanetriol (although the latter is usually high) should show a preponderance of the former. The elevation of 16-hydroxy compounds in the urine is also characteristic. The plasma steroids having the delta 5-3 beta-ol configuration should be elevated to an extent not seen in any other disorder except with an adrenal tumor. Specifically, plasma 17-hydroxypregnenolone levels will be extremely elevated, as will DHEA and the DHEAS levels. In the initial stage of diagnosis, one might initiate the work-up by determining the plasma DHEA and DHEAS concentrations so that, when these are distinctly elevated, one may proceed to further study. In the extremely mild forms it will probably be necessary to apply adrenal stimulation with ACTH in order to bring the abnormal pattern into perspective.
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PMID:Acquired adrenal hyperplasia: with special reference to 3 beta-hydroxysteroid dehydrogenase. 701 26

Two distinct isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) with respect to enzymatic activity were identified in the ovine liver and kidney. 11 beta-HSD1 (the hepatic isoform) was reversible and NADP(H)-dependent. By contrast, 11 beta-HSD2 (the renal isoform) was unidirectional and NAD-dependent. Ovine placenta contained both forms of 11 beta-HSD activities. The cDNA encoding ovine 11 beta-HSD1 was cloned, and used as a probe to study 11 beta-HSD1 gene expression in fetal sheep during development. It was found that fetal and adult liver was the major site of 11 beta-HSD1 biosynthesis, and that 11 beta-HSD1 gene expression was regulated in a tissue-specific and developmentally programmed manner. Two non-functional variants of 11 beta-HSD1 were also identified. In addition, sheep kidney was unique in that both 11 beta-HSD1 mRNA and activity were absent. Although the physiological significance of 11 beta-HSD in individual fetal organs during development remains largely speculative, 11 beta-HSD in the fetal pituitary may contribute, at least in part, to the proposed resetting of cortisol negative feedback on pituitary ACTH during the last few days of gestation. In the fetal liver, the action of 11 beta-HSD may lead to the formation of cortisol which could act locally as well as systematically to modulate developmental processes. Placental 11 beta-HSD may protect fetus from exposure to the growth-inhibiting effects of maternal glucocorticoids.
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PMID:Ovine 11 beta-hydroxysteroid dehydrogenase: from gene to function. 758

Two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) have been described which catalyze the interconversion of cortisol (F) to cortisone (E). 11 beta HSD activity has previously been reported in placenta and fetal membranes, where its role may be to protect the developing fetus from glucocorticoid excess. Furthermore, in the rat, an association between placental 11 beta HSD activity and the subsequent development of hypertension in the offspring has been reported. We have characterized the isoforms of 11 beta HSD in human fetal membranes and dissected placental tissue at term and investigated the relationship between placental 11 beta HSD activity and fetal and placental weights. 11 beta HSD activity studies in the presence of 0.1 mumol/L F and NAD (indicative of type 2 isoform activity) revealed high levels of activity in trophoblast dissected free of vessels (561 +/- 87 pmol E/h.mg protein; n = 4) > undissected placenta > cotyledenous vessels dissected away from trophoblast > placental and reflected amnion. In contrast, in the presence of 2.5 mumol/L F and NADP (indicative of type 1 isoform activity), only decidua and chorion demonstrated significant levels of 11 beta HSD activity. Type 1 11 beta HSD activity in chorion was probably due to decidual contamination, in that it was absent in decidua-free fused chorion obtained from a twin pregnancy. In keeping with these data, type 1 11 beta HSD messenger ribonucleic acid (1.5 kilobases) was detected in decidua, but in no other tissue, and high levels of type 2 11 beta HSD messenger ribonucleic acid (1.9 kilobases) were found in undissected placenta and trophoblast. In 27 term placentas, 11 beta HSD activity varied from 194-448 pmol E/h.mg protein. There was a weak, but significant, positive correlation between term placental 11 beta HSD activity and fetal weight (r = 0.408; P = 0.034), but no correlation with placental weight. Thus, in man, the reported association of a small fetus and a large placenta predisposing to adult hypertension cannot be explained on the basis of defective 11 beta HSD activity. However, the placenta offers an immense reservoir for F clearance (1.73-7.95 mumol/min.placenta) and may be a principal factor driving fetal ACTH secretion and, hence, fetal adrenal steroidogenesis.
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PMID:Type 2 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid and activity in human placenta and fetal membranes: its relationship to birth weight and putative role in fetal adrenal steroidogenesis. 788 47

Nonclassical 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase deficiency (NC3 beta HSDD) has been diagnosed in hyperandrogenic women with an increasing frequency during the last 14 yr. Fifteen menarcheal women with androgen excess syndrome, diagnosed with NC3 beta HSDD previously were restudied, in 12 after discontinuation of glucocorticoid treatment, in 2 patients never treated with glucocorticoids, and in 1 both before and after glucocorticoid therapy. Each of the 15 patients underwent ACTH stimulation testing, in some cases on multiple occasions. Although some (very few) patients seem to have improved with time, others remained the same or got worse. Molecular DNA analysis was also performed in 6 of the patients, using the strategy successfully used to detect point mutations in the type II 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) gene, which are responsible for classical 3 beta HSD deficiency. This strategy consists of the direct sequencing of polymerase chain reaction-amplified DNA fragments corresponding to the complete coding sequence and all intron-exon junctions and to the 5'- and 3'-noncoding region of this gene. We were unable to demonstrate any mutation of the type II 3 beta HSD gene in these 6 patients. To gain additional information about potential mutations, direct sequencing of the type I 3 beta HSD gene was also performed using this same strategy, and no mutations were found. The present study strongly suggests that unlike the salt-losing and nonsalt-losing forms of classical 3 beta HSD deficiency, NC3 beta HSDD is not due to a mutant type II 3 beta HSD enzyme. However, the possibility remains of a mutation(s) in the unsequenced regions of the type II 3 beta HSD gene or elsewhere, such as in a gene for modulatory protein, playing a specific role in the expression of the type II 3 beta HSD gene. On the other hand, knowing the multiple hormonal controls to which 3 beta HSD activity is subject, it cannot be excluded that at least in some cases, NC3 beta HSDD may be an acquired defect, the result of endogenous or environmental factors.
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PMID:No evidence of mutations in the genes for type I and type II 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) in nonclassical 3 beta HSD deficiency. 798 89

ACTH independent bilateral macronodular adrenocortical hyperplasia (AIMAH) is associated with autonomous hypercortisolism. We report six cases of AIMAH, in which immunohistochemical studies on steroidogenic enzymes (P450scc, 3 beta HSD, P450c21, P450c17, P450c11) were performed on surgically resected adrenal glands. In situ hybridization studies of P450c17 were performed in two cases in order to localize the sites of steroidogenesis. Immunoreactivity to P450scc, P450c21, and P450c11 was observed in both clear and compact cortical cells, with compact cells displaying more intense staining, as reported in Cushing's adenoma and ACTH dependent bilateral adrenocortical hyperplasia. Immunoreactivity to P450c17 was observed predominantly in small compact cells, whereas that to 3 beta HSD occurred exclusively in clear cortical cells. In situ hybridization also demonstrated that P450c17 was localized in small compact cortical cells. This differential expression of 3 beta HSD and P450c17 in clear and compact cortical cells has been observed only in AIMAH among adrenocortical disorders. This ineffective corticosteroidogenesis may contribute to the relatively low production of cortisol. AIMAH should therefore be considered as a distinct subtype of primary adrenocortical Cushing's syndrome.
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PMID:ACTH-independent macronodular adrenocortical hyperplasia: immunohistochemical and in situ hybridization studies of steroidogenic enzymes. 800 46

We report pubertal maturation and dynamic studies of gonadotropin and gonadal hormone secretion in long term glucocorticoid-treated siblings with nonsalt-wasting classic adrenal and gonadal 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) deficiency. The 18-yr-old female siblings spontaneously developed thelarche and menarche at 10 and 12 yr, respectively, and manifested irregular menses, hirsutism, and polycystic ovaries at 17 yr. The 16-yr-old male sibling spontaneously developed secondary sex characteristics at age 11 yr and exhibited Tanner IV-V pubic hair, a 6.5 x 3.0-cm surgically repaired penis, and enlarged nonnodular testes. Overnight (2200-0700 h) plasma gonadotropin (every 20 min) and gonadal steroid levels (every 2 h) under ACTH adrenal suppression revealed the following. In the male sibling, there were overall normal Tanner V male LH (3-21 mIU/mL) and FSH (1.2-13 mIU/mL) levels, normal peak frequency and amplitude of LH (70 +/- 62 min and 15 +/- 3 mIU/mL, respectively) and FSH (65 +/- 28 min and 13 +/- 3 mIU/mL), and low normal Tanner V testosterone (T) levels (11.4-17.9 nmol/L). In the female sibling, there were normal follicular phase range LH (10-28 mIU/mL) and FSH (5.1-17.2 mIU/mL) levels, normal peak frequency and amplitude of LH (96 +/- 17 min and 22 +/- 4.5 mIU/mL, respectively) and FSH (62 +/- 27 min, 13 +/- 4 mIU/mL), and early follicular phase estradiol (E2) levels (100-170 pmol/L). The LH-releasing hormone-stimulated LH response was in the normal adult range in the male and normal for the early follicular phase in the female. In contrast, ACTH and adrenal delta 5-steroid responses to CRH administration were elevated in each sibling. Gonadal suppression via Norlutin administration (30 mg/day for 3 days) after prolonged adrenal suppression by dexamethasone resulted in suppression of dehydroepiandrosterone (DHEA) and E2 in the female and DHEA and T in the male. Gonadal stimulation via hCG administration (5000 IU/day for 3 days, im) during continuous adrenal suppression resulted in a low E2 response in the female (200 pmol/L; control, 295-660 pmol/L) and a low T response in the male (15.3 nmol/L; control, 17-39 nmol/L), whereas delta 5-17-hydroxypregnenolone and DHEA levels rose 2- to 4.7-fold in each sibling. In conclusion, despite partial gonadal 3 beta HSD deficiency, the dynamics of gonadotropin and gonadal hormone secretion in these siblings indicate the absence of increased LH secretion, in contrast to the markedly increased ACTH secretion resulting from adrenal 3 beta HSD deficiency.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hypothalamic-pituitary-gonadal axis function in pubertal male and female siblings with glucocorticoid-treated nonsalt-wasting 3 beta-hydroxysteroid dehydrogenase deficiency congenital adrenal hyperplasia. 807 18


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