The aim of the present study was to investigate the expression changes of three steroidogenic enzymes in the polycystic ovary syndrome (PCOS). Thirty Sprague-Dawley (SD) rats were randomly divided into normal control (NC) group and PCOS group. PCOS rat model was established by DHEA injection. The serum levels of progesterone, estrogen and testosterone were measured by immunoradioassay or enzyme immunoassay. The cellular distributions of 3β-hydroxy steroid dehydrogenase (3β-HSD), 17β-hydroxy steroid dehydrogenase (17β-HSD) and cytochrome P450 aromatase (P450arom) in ovaries were detected by immunohistochemistry. The expression levels of 3β-HSD, 17β-HSD and P450arom were detected by RT-PCR and Western blot. The results showed that the serum levels of estrogen and testosterone of PCOS group were significantly higher than those of the NC group. There was no significant difference of serum progesterone level between the PCOS and NC groups. Compared with the NC group, the PCOS group showed increased mRNA and protein expressions of both 3β-HSD and 17β-HSD, as well as reduced P450arom mRNA and protein expressions. These results suggest that 3β-HSD and 17β-HSD, but not P450arom, may participate in the ovarian hormonal regulation in the present rat model of PCOS.
17-Hydroxysteroid Dehydrogenases ; metabolism ; 3-Hydroxysteroid Dehydrogenases ; metabolism ; Animals ; Aromatase ; metabolism ; Disease Models, Animal ; Estrogens ; blood ; Female ; Polycystic Ovary Syndrome ; enzymology ; Progesterone ; blood ; Rats ; Rats, Sprague-Dawley ; Testosterone ; blood

Glycyrrhizic acid is a component of licorice. It can cause hypokalemia through the inhibition of 11beta-hydroxysteroid dehydrogenase. The severity of symptoms depends on the dose and duration of licorice intake, as well as the individual susceptibility. The safe dose of licorice is 10 mg per day. Even a small amount of licorice can cause side effects, including hypokalemia in patients taking diuretics, with diarrhea, or congestive heart failure. We experienced a 59-year-old male with muscle weakness. He had ingested losartan and indapamide due to hypertension. At presentation, he had ingested 8 mg of licorice daily for the previous 17 days. The patient presented with severe hypokalemia (1.8 mEq/L) and rhabdomyolysis. His renin activity was 0.44 ng/mL/h, and his aldosterone level was 6.0 pg/mL. After cessation of licorice and indapamide, his potassium level recovered. In conclusion, even a small amount of licorice can induce hypokalemia in patients who are taking diuretics.
11-beta-Hydroxysteroid Dehydrogenases ; Aldosterone ; Diarrhea ; Diuretics ; Glycyrrhiza ; Glycyrrhizic Acid ; Heart Failure ; Humans ; Hypertension ; Hypokalemia ; Indapamide ; Losartan ; Male ; Middle Aged ; Muscle Weakness ; Potassium ; Renin ; Rhabdomyolysis

Adipose tissue inflammation is considered a major contributing factor in the development of obesity-associated insulin resistance and cardiovascular diseases. However, the cause of adipose tissue inflammation is presently unclear. The role of mitochondria in white adipocytes has long been neglected because of their low abundance. However, recent evidence suggests that mitochondria are essential for maintaining metabolic homeostasis in white adipocytes. In a series of recent studies, we found that mitochondrial function in white adipocytes is essential to the synthesis of adiponectin, which is the most abundant adipokine synthesized from adipocytes, with many favorable effects on metabolism, including improvement of insulin sensitivity and reduction of atherosclerotic processes and systemic inflammation. From these results, we propose a new hypothesis that mitochondrial dysfunction in adipocytes is a primary cause of adipose tissue inflammation and compared this hypothesis with a prevailing concept that “adipose tissue hypoxia” may underlie adipose tissue dysfunction in obesity. Recent studies have emphasized the role of the mitochondrial quality control mechanism in maintaining mitochondrial function. Future studies are warranted to test whether an inadequate mitochondrial quality control mechanism is responsible for mitochondrial dysfunction in adipocytes and adipose tissue inflammation.
11-beta-Hydroxysteroid Dehydrogenases ; Adipocytes ; Adipocytes, White ; Adipokines ; Adiponectin ; Adipose Tissue ; Anoxia ; Cardiovascular Diseases ; Homeostasis ; Inflammation ; Insulin Resistance ; Metabolism ; Mitochondria ; Nitric Oxide ; Obesity ; Quality Control

<b>AIMb>To study the effects of L-tyrosine on 3beta-HSD activity of rat luteal cells in vitro.

<b>METHODSb>Luteal cells were isolated from ovary tissues of female rats pretreated with PMSG and hCG. Luteal cells were cultured with 95% oxygen and 5% carbon dioxide in 37 degrees C. 3beta-HSD activity was measured by radioimmunoassay (RIA).

<b>RESULTSb>(1) 0.2 mmol x L(-1) and 2.0 mmol x L(-1) L-tyrosine significantly inhibited 3beta-HSD activity. (2) 0.2 mmol x L(-1) L-tyrosine exerted different effects on 3beta-HSD activity at different concentrations of pregnenolone (Ph). It increased 3beta-HSD activity at 0.1 micromol x L(-1) and 1 micromol x L(-1) of Pn concentration. With further increase in the concentration of Pn to 100 micromol x L(-1), the stimulating effect of L-tyrosine was switched to suppression effect. (3) L-tyrosine and L-tyrosine hydrazide both inhibited 3beta-HSD activity induced by hCG.

<b>CONCLUSIONb>L-tyrosine affects 3beta-HSD activity of rat luteal cells in vitro. L-tyrosine and tyrosine hydrazide inhibits hCG induced 3beta-HSD activity.

3-Hydroxysteroid Dehydrogenases ; metabolism ; Animals ; Cells, Cultured ; Female ; Luteal Cells ; drug effects ; enzymology ; Rats ; Rats, Wistar ; Tyrosine ; pharmacology

<b>OBJECTIVEb>To investigate the expression of 17 beta-hydroxysteroid dehydrogenase type 1 (17&beta;-HSD1) in the kidney of rats and explore the capacity of the kidney for synthesizing sex hormones.

<b>METHODSb>The expressions of 17-HSD1 and sex hormones were detected by Western blotting and radioimmunoassay in rat renal cells in primary cultured for 24 and 48 h in the presence or absence of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

<b>RESULTSb>After cell culture for 24 h, the primary rat renal cells expressed a low level of 17&beta;-HSD1 (0.1843±0.076), which increased to 1.6651±0.044 (P<0.01) in response to co-stimulation by FSH and LH. Low levels of estradiol, progesterone and testosterone were also detected in rat renal cells (3.30±3.78, 62.60±12.33, and 22.12±3.36, respectively), and co-stimulation of FSH and LH significantly increased their levels to 8.50±2.64, 117.80±9.79, and 45.04±4.39, respectively (P<0.05). The levels of these hormones showed no significant differences between cells cultured for 24 h and 48 h (P>0.05).

<b>CONCLUSIONb>The rat renal cells express 17&beta;-HSD1 and are capable of stably secreting sex hormones in response to co-stimulation with FSH and LH, suggesting the capacity of the rat kidneys for synthesizing sex hormones. These findings enrich the understanding of the endocrine function of the kidney.

17-Hydroxysteroid Dehydrogenases ; metabolism ; Animals ; Cells, Cultured ; Estradiol ; biosynthesis ; Follicle Stimulating Hormone ; pharmacology ; Kidney ; enzymology ; Luteinizing Hormone ; pharmacology ; Progesterone ; biosynthesis ; Rats ; Testosterone ; biosynthesis

<b>OBJECTIVEb>This study was designed to examine the in vitro effects of fenvalerate on steroid production and steroidogenic enzymes mRNA expression level in rat granulosa cells.

<b>METHODSb>Using primary cultured rat granulosa cells (rGCs) as model, fenvalerate of various concentrations (0, 1, 5, 25, 125, 625 micromol/L) was added to the medium for 24 h. In some cases, optimal concentrations of 22(R)-hydroxycholesterol (25 micromol/L), Follicle stimulating hormone (FSH, 2 mg/L), or 8-Bromo-cAMP (1 mmol/L) were provided. Concentrations of 17 beta-estradiol(E2) and progesterone (P4) in the medium from the same culture wells were measured by RIA and the steroidogenic enzyme mRNA level was quantified by semi-quantitative RT-PCR.

<b>RESULTSb>Fenvalerate decreased both P4 and E2 production in a dose-dependent manner while it could significantly stimulate rGCs proliferation. This inhibition was stronger in the presence of FSH. Furthermore, it could not be reversed by 22(R)-hydroxycholesterol or 8-Bromo-cAMP. RT-PCR revealed that fenvalerate had no significant effect on 3 beta-HSD, but could increase the P450scc mRNA level. In addition, 17 beta-HSD mRNA level was dramatically reduced with the increase of fenvalerate dose after 24 h treatment.

<b>CONCLUSIONb>Fenvalerate inhibits both P4 and E2 production in rGCs. These results support the view that fenvalerate is considered as a kind of endocrine-disrupting chemicals. The mechanism of its disruption may involve the effects on steroidogenesis signaling cascades and/or steroidogenic enzyme's activity.

3-Hydroxysteroid Dehydrogenases ; analysis ; metabolism ; 8-Bromo Cyclic Adenosine Monophosphate ; pharmacology ; Animals ; Base Sequence ; Cells, Cultured ; Dose-Response Relationship, Drug ; Estradiol ; analysis ; metabolism ; Female ; Follicle Stimulating Hormone ; pharmacology ; Granulosa Cells ; cytology ; drug effects ; metabolism ; Hydroxycholesterols ; pharmacology ; Nitriles ; pharmacology ; Progesterone ; analysis ; metabolism ; Pyrethrins ; pharmacology ; RNA, Messenger ; analysis ; metabolism ; Rats ; Steroids ; metabolism

The present study was aimed at investigating the role of type II 11beta-hydroxysteroid dehydrogenase (IIbeta- HSD II) in the development of hypertension. Two-kidney, one-clip (2K1C), deoxycorticosterone acetate (DOCA)/salt, or NG-nitro-L-arginine methyl ester (L-NAME) hypertension was induced in male Sprague- Dawley rats. Four weeks later, the expression of 11beta-HSD II mRNA was determined in the kidney by Northern blot analysis. The plasma level of aldosterone was measured by radioimmunoassay. In 2K1C hypertension, the expression of 11beta-HSD II was decreased in the clipped kidney and increased in the non-clipped kidney. The expression was increased in the remnant kidney of DOCA/salt hypertension, while decreased in the kidneys of L-NAME hypertension. The plasma level of aldosterone was increased, decreased, and remained unchanged in 2K1C, DOCA/salt, and L-NAME hypertension, respectively. The down-regulation of 11beta-HSD II may contribute to the sodium retention, thereby increasing the blood pressure in 2K1C and L-NAME hypertension. On the contrary, the up-regulation in DOCA/salt hypertension may play a compensatory role to dissipate the sodium retention.
11-beta-Hydroxysteroid Dehydrogenases* ; Aldosterone ; Animals ; Blood Pressure ; Blotting, Northern ; Desoxycorticosterone ; Down-Regulation ; Humans ; Hypertension* ; Kidney* ; Male ; NG-Nitroarginine Methyl Ester ; Plasma ; Radioimmunoassay ; Rats* ; RNA, Messenger ; Sodium ; Up-Regulation

Nephrotic syndrome and liver cirrhosis are common clinical manifestations, and are associated with avid sodium retention leading to the development of edema and ascites. However, the mechanism for the sodium retention is still incompletely understood and the molecular basis remains undefined. We examined the changes of sodium (co)transporters and epithelial sodium channels (ENaCs) in the kidneys of experimental nephrotic syndrome and liver cirrhosis. The results demonstrated that puromycin- or HgCl2?induced nephrotic syndrome was associated with 1) sodium retention, decreased urinary sodium excretion, development of ascites, and increased plasma aldosterone level; 2) increased apical targeting of ENaC subunits in connecting tubule and collecting duct segments; and 3) decreased protein abundance of type 2 11beta-hydroxysteroid dehydrogenase (11betaHSD2). Experimental liver cirrhosis was induced in rats by CCl4 treatment or common bile duct ligation. An increased apical targeting of alpha-, beta-, and gamma-ENaC subunits in connecting tubule, and cortical and medullary collecting duct segments in sodium retaining phase of liver cirhosis but not in escape phase of sodium retention. Immunolabeling intensity of 11betaHSD2 in the connecting tubule and cortical collecting duct was significantly reduced in sodium retaining phase of liver cirrhosis, and this was confirmed by immunoblotting. These observations therefore strongly support the view that the renal sodium retention associated with nephrotic syndrome and liver cirrhosis is caused by increased sodium reabsorption in the aldosterone sensitive distal nephron including the connecting tubule and collecting duct, and increased apical targeting of ENaC subunits plays a role in the development of sodium retention in nephrotic syndrome and liver cirrhosis.
11-beta-Hydroxysteroid Dehydrogenases ; Aldosterone ; Animals* ; Ascites ; Common Bile Duct ; Edema ; Epithelial Sodium Channels ; Immunoblotting ; Kidney ; Ligation ; Liver Cirrhosis* ; Liver Cirrhosis, Experimental ; Liver* ; Models, Animal* ; Nephrons ; Nephrotic Syndrome* ; Plasma ; Rats ; Sodium ; United Nations

A high intake of licorice can cause hypermineralocorticoidism with sodium retention and potassium loss, edema, increased blood pressure and depression of renin-angiotensin-aldosterone system. Glycyrrhizic acid, a component of licorice, produces hypermineralocorticoidism through the inhibition of 11beta-hydroxysteroid dehydrogenase. We report a 55-year-old woman with severe muscle weakness with hypokalemia(Serum K+ : 1.7 mEq/ L) due to raw licorice tea. She boiled the licorice 50 g in water and drunk intermittently for 4 months due to her foreign body sensation on her throat. In Korea there is a traditional recipe that licorice works out for the above symptom. Her serum renin activity and aldosterone level were far beyond normal range which was typical to licorice ingestion. She also had metabolic alkalosis with pH 7.55 and hypertension. After quitting the licorice, hypokalemia and muscle weakness gradually improved and her blood pressure returned to normal.
11-beta-Hydroxysteroid Dehydrogenases ; Aldosterone ; Alkalosis ; Blood Pressure ; Depression ; Eating ; Edema ; Female ; Foreign Bodies ; Glycyrrhiza* ; Glycyrrhizic Acid ; Humans ; Hydrogen-Ion Concentration ; Hypertension ; Hypokalemia* ; Korea ; Middle Aged ; Muscle Weakness ; Pharynx ; Potassium ; Reference Values ; Renin ; Renin-Angiotensin System ; Sensation ; Sodium ; Tea ; Water

This paper was designed to observe the colocalization of 11beta-HSD1 and GR, and its significance in the rat hippocampus. Immunocytochemical dual-staining showed that not only 11beta-HSD1 but also GR immunoreactive substances were present in the cultured rat hippocampal neurons. Moreover, they were colocalized in the same hippocampal neuron. Synthetic glucocorticoid dexamethasone (DEX) up-regulated the protein expression and activity of 11beta-HSD1 in the cultured hippocampal neurons, as determined by Western blot and thin layer chromatography (TLC) respectively. The transfection of PC12 cells with the plasmid containing promoter sequence of 11beta-HSD1 gene and the reporter gene of CAT enzyme was conducted. DEX up-regulated the reporter gene expression in the system described above. The up-regulation of 11beta-HSD1 and reporter gene expression induced by DEX were both blocked by GR antagonist RU38486. Our study suggests that the colocalization of 11beta-HSD1 and GR in the hippocampus may be implicated in the up-regulation of 11beta-HSD1 expression by glucocorticoids combining to its promoter region, which in turn produces more biologically active glucocorticoids necessary for the binding of low affinity of GR.
11-beta-Hydroxysteroid Dehydrogenases ; genetics ; metabolism ; Animals ; Animals, Newborn ; Dexamethasone ; pharmacology ; Gene Expression Regulation ; Hippocampus ; cytology ; metabolism ; Mifepristone ; pharmacology ; Neurons ; chemistry ; metabolism ; PC12 Cells ; Promoter Regions, Genetic ; Rats ; Receptors, Glucocorticoid ; genetics ; metabolism ; Transfection