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: EC:1.1.1.3 (HSD)
3,464 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of membrane phospholipids in testicular androgen biosynthesis was investigated by monitoring the effects of phospholipase treatments on the activities of the steroid transforming enzymes. Androgen biosynthesis in untreated rat testicular microsomes was examined by monitoring the temporal appearance of pregnenolone metabolites and was found to proceed through the 4-ene route. When phospholipase A2 was included, the 5-ene steroids 17-hydroxypregnenolone and dehydroepiandrosterone (DHEA) were formed in greater quantities, and the production of 4-ene steroids was reduced indicating that the conversion of 5-ene steroids to the 4-ene configuration was inhibited by phospholipase A2 treatment. Phospholipase C, in addition to inhibiting this step, also inhibited the conversion of C21 steroids to C19 steroids. When the enzymatic steps were measured individually, phospholipase A2 inhibited 3 beta-hydroxysteroid dehydrogenase-isomerase (3 beta-HSD-Isomerase) with an ED50 of 73 mU/ml but had no effect on the activities of 17-hydroxylase, C-17, 20 lyase, or 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD). However, though phospholipase C treatment inhibited 3 beta-HSD-Isomerase, it caused less inhibition (the ED50 value was 149 mU/ml). Furthermore, 17-hydroxylase and C-17, 20 lyase activities were also inhibited by phospholipase C treatment (ED50 values were 410 and 343 mU/ml, respectively), but no effect on 17 beta-HSD was observed. The differences in the apparent phospholipid requirements of the steroidogenic enzymes provides the possibility that the metabolic fate of pregnenolone may be regulated by changes in the phospholipid composition of the microenvironment.
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PMID:Phospholipases modulate the rat testicular androgen biosynthetic pathway in vitro. 284 83

Leydig cells from roe-deer collected according to Steinberger's (1975) technique were cultured as monolayers in Leighton tubes for 10 days. Cultures were grown in medium 199 supplemented with 10% calf serum. Androgen and oestrogen secretion by Leydig cells into the culture medium was measured using appropriate radio-immunoassays. Using histochemical tests the activity of the following oxydoreductive enzymes in cultured Leydig cells was shown: delta 5, 3 beta-hydroxysteroid dehydrogenase (delta 5, 3 beta-HSD), 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD), succinate and lactate dehydrogenases (SDH and LDH). Strong activity of the enzymes investigated during the first 4 days of culture was observed. The androgen level was high throughout the second and fourth day of culture. A decrease in hormone secretion after day 4 occurred, and this was closely correlated with enzyme activity. The oestrogen level was very low during culture. The direct effect of the luteinizing hormone (LH) added into the culture medium caused an increase in not only enzyme activity but also androgen and oestrogen levels.
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PMID:Hormonal secretion and enzyme activity of cultured roe-deer (Capreolus capreolus L.) Leydig cells, as measured by radio-immunological and histochemical assays. 300 Jul

Male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) deficiency has a high prevalence within the Arab population of the Gaza strip and is characterised by marked virilization at puberty, leading in many cases to the spontaneous adoption of a male gender role. As a result of this, parents of 7 affected male infants (aged 1-10 months) born with female phenotype requested early gender reassignment. Diagnosis was suspected in 5 on the basis of a positive family history, but confirmed in all cases by the finding of low to normal testosterone levels (30-184 ng/dl) with high delta 4-androstenedione levels (188-808 ng/dl), after hCG. Treatment with im testosterone oenanthate (25-50 mg/dose) was given in one to three 3-months courses and penile size was increased into the normal range without evoking a significant increase in height velocity or skeletal maturation. Five patients underwent the first stage of male genitoplasty between 2 and 3 years of age. This consisted of bilateral orchidopexy, chordee release and penile lengthening - yielding finally an anatomically normal-sized and shaped penis. Androgen responsive male pseudohermaphroditism due to 17 beta-HSD deficiency or a similar defect and diagnosed in infancy should be treated as soon as possible with systemic testosterone before considering any sex change, and in preparation for male genitoplasty. Early gender reassignment according to genetic and gonadal sex is probably the management of choice for these cases since this may result in a normal adjustment to the male gender role, particularly after puberty.
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PMID:Male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency: gender reassignment in early infancy. 301 38

Androgen and oestrogen receptors have been demonstrated in mammalian liver, but since it is generally accepted that they are probably non-functional at endogenous steroid concentrations, it is not apparent how they mediate physiological influences on this organ. Nor is it certain to what extent pharmacological actions of sex hormones reflect overstimulation of physiological routes or whether alternative mechanisms become available once threshold values have been reached. In this presentation an attempt has been made to answer some of these questions using data obtained from a study of the regulation of the activities of microsomal 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSDH) and 5 alpha-reductase in rat liver. Androgens exert their primary physiological and pharmacological influences at the level of the hypothalamus. Oestrogens can elicit three different types of effect-physiological, antiandrogenic and pharmacological--of which the first two involve primary effects on the pituitary. Hepatic oestrogen receptors only become activated when oestrogen concentrations reach pharmacological levels. Progestins probably have no physiological influence on the livers of non-pregnant rats. Their pharmacological actions may either be traced back to secondary androgenic (e.g. medroxyprogesterone acetate, levonorgestrel) or oestrogenic (e.g. norethynodrel, lynestrenol) properties, involving the routes described above, or to independent effects on the central nervous system (e.g. cyproterone acetate modulation of 5 alpha-reductase activity).
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PMID:Mechanisms of physiological and pharmacological sex hormone action on the mammalian liver. 332 May 49

In order to investigate the mode of action of testosterone (T) on human hair follicles we studied the metabolism of T and localization of androgen receptors in outer root sheath cells (ORSC) and dermal papilla cells (DPC) from different body sites. T was principally metabolized to androstenedione (delta 4) even in beard ORSC as well as epidermal keratinocytes (EK), and the ratio of apparent 5 alpha-reductase (5 alpha-R) to 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) did not differ between these two kinds of cells. The 5 alpha-R activity in beard DPC was 3 times as high as that in occipital scalp and axillary DPC. The 5 alpha-R of beard DPC exhibited a narrow optimum pH of 5.5, which is characteristic of type 2 enzyme present in androgen target cells. In contrast, 5 alpha-R of DPC from axillary and occipital scalp hair showed a broad optimum pH range between 6.5-9.0 corresponding to type 1 5 alpha-R. Androgen receptors were detected in the DPC of beard and axillary hair follicles, but not in those of occipital scalp hair follicles using immunohistochemical staining with polyclonal anti-androgen receptor antibody. Epithelial cells of the hair bulb were not stained by the antibody. Androgen receptors were also detected in the nuclei of cultured beard and axillary DPC, but the DPC from occipital scalp hair follicles showed little staining with the antibody. We also examined the effects of T on the DNA synthesis and proliferation of cultured ORSC and DPC. T did not have a proliferative effect on either type of cell when cultured alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of action of androgen in hair follicles. 799 80

The presented overview gives clear evidence for steroids as local regulators of follicular and luteal activity. In the follicle, estrogen receptor-alpha (ERalpha) and ERbeta expression are demonstrated in cow, ewe and pig. Besides species specific effects in general, there is evidence that estradiol-17beta (E(2)) exerts a dose-dependent inhibition on the secretion of progesterone (P(4)) by both theca interna cells (TI) and granulosa cells (GC). GC enhance the ability of the TI to produce androstendione by supplying them with progestin precursor. Androgen produced by TI enhances the ability of the GC to make E(2), and high concentrations of E(2) in the preovulatory follicle inhibit 3beta-HSD in both TI and GC and thus, may promote the use of the pathway Delta(5) for TI androgen production. The authors suggest that E(2) acts within the follicle to exert positive feedback on androgen and E(2) production, and exerts mitotic and anti-atretic or anti-apoptotic effects on follicular cells. Parts of the E(2)-mediated local action are regulated by stimulating effects on hormone receptors (LH, FSH, oxytocin). Gap junctions permit transfer of nutrients and cytokines to and from the avascular GC and oocyte, and formation is stimulated by estrogens. In bovine corpus luteum (CL) there is evidence that P(4) may directly regulate the production of P(4), oxytocin and prostaglandins (PGs) in a cycle dependent fashion. In most of domestic animal species, there is clear evidence for CL production of E(2) with clear stimulatory and luteotropic effects on P(4), and an intraluteal circuit that involves paracrine effects of E(2), oxytocin and PGF(2alpha) (especially in pigs). In contrast, there are species (ruminants, mares) in which the evidence for important local effects of E(2) is less clear, although expression of ERalpha, ERbeta and progesterone receptor (PR) is documented. Progesterone is very important for the regulation of CL lifetime by effects on the endometrium and release of the luteolytic signal PGF(2alpha). In conclusion, steroids as local regulators of ovarian activity are now documented and may stimulate further research in this field.
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PMID:Steroids as local regulators of ovarian activity in domestic animals. 1214 26

The aim of the present study was to determine the effect of the composition of dietary fatty acids, the duration of feeding period and dietary fat level on androgen metabolism in male rats. One hundred and twelve Wistar rats were divided into 18 groups which were fed three diets containing different types of fat (rapeseed [R], palm [P] and fish [F] oil) at either normal fat level (w/w; 5%) or high fat level (20%) during one, three or six weeks. Blood plasma level of androgen (testosterone+dihydrotestosterone) and testicular activity of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) were investigated. In addition, androgen content in cytosol of the heart, the target organ, was measured. Androgen concentration in both blood plasma and heart cytosol extracts was measured by radioimmunoassay. The activity of 17Beta-HSD was expressed as a conversion of [3H]androstendione to [3H]testosterone in soluble fraction of gonadal homogenates. Plasma androgen concentration was influenced by a type of dietary fat (p<0.05). The highest plasma level of androgen was observed in animals fed R diets rich in unsaturated fatty acids. Significantly lower androgen concentration was demonstrated in rats fed P diets rich in saturated fatty acids. Only the feeding period factor significantly influenced androgen content in cytosol fraction of heart muscle cells (p<0.01). A positive correlation was found between plasma androgen concentration in plasma and cytosol fraction of the heart muscle cells (r=0.63, p<0.001). The feeding period (p<0.001) and dietary fat type (p<0.05) significantly affected the activity of 17beta-HSD. The least 17beta-HSD activity was observed in animals consuming the P-20% diet for six weeks. In summary, dietary fat type and feeding period, but not fat level, significantly affected both testosterone production and testosterone uptake by the target organ in male rats. It was found that a rapeseed diet rich in unsaturated fatty acids stimulated the testicular function in rats.
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PMID:Influence of dietary fatty acids composition, level of dietary fat and feeding period on some parameters of androgen metabolism in male rats. 1466 50

Androgen production in the testis is carried out by the Leydig cells, which convert cholesterol into androgens. Previously, isoflavones have been shown to affect serum androgen levels and steroidogenic enzyme activities. In this study, the effects of lifelong exposure to dietary soy isoflavones on testicular microsomal steroidogenic enzyme activities were examined in the rat. F1 male rats were obtained from a multi-generational study where the parental generation was fed diets containing alcohol-washed soy protein supplemented with increasing amounts of Novasoy, a commercially available isoflavone supplement. A control group was maintained on a soy-free casein protein-based diet (AIN93G). The diets were designed to approximate human consumption levels and ranged from 0 to 1046.6 mg isoflavones/kg pelleted feed, encompassing exposures representative of North American and Asian diets as well as infant fed soy-based formula. Activities of testicular 3beta-hydroxysteroid dehydrogenase (3beta-HSD), P450c17 (CYP17), 17beta-hydroxysteroid dehydrogenase (17beta-HSD) were assayed on post natal day (PND) 28, 70, 120, 240 and 360 while 5alpha-reducatase was assayed on PND 28. At PND 28, 3beta-HSD activity was elevated by approximately 50% in rats receiving 1046.6 mg total isoflavones/kg feed compared to those on the casein only diet. A similar increase in activity was observed for CYP17 in rats receiving 235.6 mg total isoflavones/kg feed, a level representative of infant exposure through formula, compared to those receiving 0mg isoflavones from the casein diet. These results demonstrate that rats fed a mixture of dietary soy isoflavones showed significantly altered enzyme activity profiles during development at PND 28 as a result of early exposure to isoflavones at levels obtainable by humans.
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PMID:Altered testicular microsomal steroidogenic enzyme activities in rats with lifetime exposure to soy isoflavones. 1569 48

The third annual meeting of the Androgen Excess Society, held in San Diego, California, June 3, 2005, reported on new developments in the field, including intrafollicular steroidogenesis, intrathecal biochemistry, mechanisms of insulin signal and resistance of polycystic ovary syndrome, and novel aspects of androgen signaling. The experience of the 21-OH-deficient Nonclassical Adrenal Hyperplasia (NCAH) Multicenter Study Group was also discussed, along with a keynote presentation on the molecular aspects of 3beta-HSD-deficient NCAH.
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PMID:Report on the Third Annual Meeting of the Androgen Excess Society, San Diego, California, June 3, 2005. 1707 Jan 90

Androgen deprivation is commonly used in the treatment of metastatic prostate cancer. The (-)-gossypol enantiomer has been demonstrated as an effective inhibitor of Bcl-2 in the treatment of prostate cancer. However, the mechanism of gossypol as an inhibitor of androgen biosynthesis is not clear. The present study compared (+)- and (-)-gossypols in the inhibition of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-HSD isoform 3 (17beta-HSD3) in human and rat testes. Gossypol enantiomers were more potent inhibitors of rat 3beta-HSD with IC(50)s of approximately 0.2microM compared to 3-5microM in human testes. However, human 17beta-HSD3 was more sensitive to inhibition by gossypol enantiomers, with IC(50)s of 0.36+/-0.09 and 1.13+/-0.12 for (-)- and (+)-gossypols, respectively, compared to 3.43+/-0.46 and 10.93+/-2.27 in rat testes. There were species- and enantiomer-specific differences in the sensitivity of the inhibition of 17beta-HSD3. Gossypol enantiomers competitively inhibited both 3beta-HSD and 17beta-HSD3 by competing for the cofactor binding sites of these enzymes. Gossypol enantiomers, fed orally to rats (20mg/kg), inhibited 3beta-HSD but not 17beta-HSD3. This finding was consistent with the in vitro data, in which rat 3beta-HSD was more sensitive to gossypol inhibition than rat 17beta-HSD3. As the reverse was true for the human enzymes, gossypol might be useful for treating metastatic prostate cancer.
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PMID:The (+)- and (-)-gossypols potently inhibit both 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase 3 in human and rat testes. 1942 56


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