17 beta-hydroxysteroid dehydrogenase 3 deficiency due to novel compound heterozygous variants of HSD17B3 gene in a sib pair / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a sib pair featuring 17beta-hydroxysteroid dehydrogenase type 3 deficiency.@*METHODS@#Genomic DNA was extracted from the proband, her sister, and their parents, and was subjected to sequencing analysis with a gene panel for sexual development. Suspected variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#Both the proband and her sister were found to harbor novel compound heterozygous missense variants of the HSD17B3 gene, namely c.839T>C (p.Leu280Pro) and c.239G>T (p.Arg80Leu), which were derived respectively from their mother and father. The variants were unreported previously and predicted to be deleterious by PolyPhen2, MutationTaster and other online software. Based on the American College of Medical Genetics and Genomics standards and guidelines, both c.839T>C(p.Leu280Pro) and c.239G>T (p.Arg80Leu) were predicted to be likely pathogenic (PM2+PP1+PP2+PP3+PP4, PM2+PM5+PP1+PP2+PP3+PP4).@*CONCLUSION@#The compound heterogeneous variants of the HSD17B3 gene probably underlay the disease in this sib pair. 17beta-hydroxysteroid dehydrogenase type 3 deficiency may lack specific clinical features and laboratory index, genetic testing can facilitate a definitive diagnosis.

Omic studies reveal the pathogenic lipid droplet proteins in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is an epidemic metabolic condition driven by an underlying lipid homeostasis disorder. The lipid droplet (LD), the main organelle involved in neutral lipid storage and hydrolysis, is a potential target for NAFLD therapeutic treatment. In this review, we summarize recent progress elucidating the connections between LD-associated proteins and NAFLD found by genome-wide association studies (GWAS), genomic and proteomic studies. Finally, we discuss a possible mechanism by which the protein 17β-hydroxysteroid dehydrogenase 13 (17β-HSD13) may promote the development of NAFLD.

Expression of 17 beta-hydroxysteroid dehydrogenase type 1 in the kidney of rats: the capacity of the kidney for synthesizing sex hormones / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of 17 beta-hydroxysteroid dehydrogenase type 1 (17β-HSD1) in the kidney of rats and explore the capacity of the kidney for synthesizing sex hormones.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>After cell culture for 24 h, the primary rat renal cells expressed a low level of 17β-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).</p><p><b>CONCLUSION</b>The rat renal cells express 17β-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.</p>

novel mutation causing 17-beta-hydroxysteroid dehydrogenase type 3 deficiency in an Omani child: first case report and review of literature

This is the first case report in Oman and the Gulf region of a 17-beta-hydroxysteroid dehydrogenase type 3 [17-beta-HSD3] deficiency with a novel mutation in the HSD17B3 gene that has not been previously described in the medical literature. An Omani child was diagnosed with 17-beta-HSD3 deficiency and was followed up for 11 years at the Pediatric Endocrinology Clinic, Royal Hospital, Oman. He presented at the age of six weeks with ambiguous genitalia, stretched penile and bilateral undescended testes. Ultrasound showed no evidence of any uterine or ovarian structures with oval shaped solid structures in both inguinal regions that were confirmed by histology to be testicular tissues with immature seminiferous tubules only. The diagnosis was made by demonstrating low serum testosterone and high androstenedione, estrone, and androstenedione:testosterone ratio. Karyotyping confirmed 46,XY and the infant was raised as male. Testosterone injections [25 mg once monthly] were given at two and six months and then three months before his surgeries at five and seven years of age when he underwent multiple operations for orchidopexy and hypospadias correction. At the age of 10 years he developed bilateral gynecomastia [stage 4]. Laboratory investigations showed raised follicle-stimulating hormone, luteinizing hormone, androstenedione, and estrone with low-normal testosterone and low androstendiol glucurunide. Testosterone injections [50 mg once monthly for six months] were given that resulted in significant reduction in his gynecomastia. Molecular analysis revealed a previously unreported homozygous variant in exon eight of the HSD17B3 gene [NM_000197.1:c.576G>A.Trp192*]. This variant creates a premature stop codon, which is very likely to result in a truncated protein or loss of protein production. This is the first report in the medical literature of this novel HSD17B3 gene mutation. A literature review was conducted to identify the previous studies related to this disorder

Establishment of a rotary aerobic culture system for in vitro culture of mouse testis / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish an in vitro model of cultured mouse testis using rotary aerobic culture.</p><p><b>METHODS</b>Rotary aerobic incubation with optimized culture conditions was used for in vitro culture of mouse testis, and the morphology of the cultured testicular tissues was compared with that cultured in Transwell chambers. The changes in the testicular tissue structure were examined using HE staining, and the cell proliferation was assessed with BrdU staining. Testosterone concentrations in the culture medium were tested with radioimmunoassay and the expression of the functionally related proteins in the testis was detected using immunohistochemistry.</p><p><b>RESULTS</b>The testicular tissue cultured by optimized rotary aerobic culture presented with more intact histological structure with the size of the testis ranged from 0.3 to 0.8 mm(3). In the two culture systems, the prolifeation index of the spermatogonia increased and that of Sertoli cells decreased with time, and such changes in spermatogonia and Sertoli cell proliferation indices became statistically significant at 3 days (P<0.05) and 5 days (P<0.05) of culture, respectively, as compared with those at 1 day. The concentration of testoerone in the culture media decreased significantly with incubation time (P<0.05). At 3 days of culture, the protein expression of 3β-hydroxysteroid dehydrogenase, cytochrome P450 17α-hydroxylase and cholesterol side-chain cleavage enzyme was detected in Leydig cell cytoplasm and vimentin expression in Sertoli cell cytoplasm.</p><p><b>CONCLUSION</b>An in vitro model of cultured mouse testis has been successfully established using rotary aerobic incubation.</p>

Effect of genistein combined with anastrozole on mammary tumors in ovariectomized rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the inhibitory effect of genistin combined with anastrozole on the growth and apoptosis of breast tumor tissue, and to study their anti-cancer mechanism by using the model of 7,12-dimethylbenz [alpha] anthracene (DMBA)-induced mammary tumors following ovariectomy in Sprague-Dawley (SD) rats.</p><p><b>METHODS</b>The DMBA induced postmenopausal SD rats were randomly divided into the control group, the genistein group, the anastrozole group, and the genistein combined with anastrozole group. The growth of tumors was observed in each group. The proliferation index and apoptosis index of tumor cells were determined. Moreover, estradiol (E2) and 17beta-HSD1 mRNA levels were determined by ELISA and RT-PCR respectively.</p><p><b>RESULTS</b>The tumor growth was inhibited in the genistein group and the anastrozole group. The inhibitory ratio was significantly higher in the genistein combined with anastrozole group (P < 0.05). Compared with the control group, levels of E2 and 17beta-HSD1 mRNA decreased more significantly in the genistein combined with anastrozole group (P < 0.05).</p><p><b>CONCLUSIONS</b>Genistein could suppress the growth of mammary tumors in postmenopausal rats. It showed synergistic effect when combined with anastrozole, which resulted in reduced levels of E2 and 17beta-HSD1 mRNA. It had inhibitory effect on the growth of breast tumors.</p>

Expression of steroidogenic enzymes in the rat model of polycystic ovary syndrome / 生理学报

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.

Decreased Expression of Type 5 17beta-Hydroxysteroid Dehydrogenase (AKR1C3) Protein Identified in Human Diabetic Skin Tissue

BACKGROUND: Diabetes is characterized by chronic hyperglycemia, and hyperglycemia can increase reactive oxygen species (ROS) production from the mitochondrial electron transport chain. The formation of ROS in cells induces oxidative stress and activates oxidative damage-inducing genes. There is no research on the protein levels of oxidative damage-related genes AKR1C3 in human diabetic skin. We explored the expression of AKR1C3 in diabetic skin compared with normal skin tissue. OBJECTIVE: To compare the expression of AKR1C3 in normal skin versus diabetic skin. METHODS: AKR1C3 expression was evaluated by western blotting in 6 diabetic skin tissue samples and 6 normal skin samples. Immunohistochemical staining was carried out to analyze AKR1C3 expression in the 6 diabetic skin tissue samples (July 2009 to December 2011; Department of Plastic and Reconstructive Surgery at Soonchunhyang University Seoul Hospital, Seoul, Korea). RESULTS: The western blotting showed a significant reduction in AKR1C3 protein expression in diabetic skin tissue compared to normal tissue. Immunohistochemical examination of AKR1C3 showed that it was weakly expressed in all diabetic skin samples. CONCLUSION: We believe that AKR1C3 is related to diabetic skin in altered metabolic states which elevate ROS production.

Effects of soluble antigen-induced immune cell activation on steroidogenesis in murine lymphoid organ.

The effect of soluble antigenic (bovine serum albumin, BSA) stimulation to induce steroidogenesis in murine lymphoid organs with concomitant changes in proinflammatory or inflammatory cytokine levels and its implication in the alteration of T-cell response was studied in the mice. Male Swiss albino mice (6-8 weeks old) with average body weight (20 +/- 4 g) were randomly assigned to 3 groups and injected with BSA in presence and absence of Freund's complete or incomplete adjuvant, whereas the control group received only saline. After 3 weeks, animals were sacrificed, and serums as well as lymphoid organs were collected. From the lymphoid tissue homogenate, the activities of steroidogenic enzymes and corticosterone and cytokine levels of the serum were estimated. Steroidogenic enzyme activities in murine lymphoid organs, as well as the pro-inflammatory and inflammatory cytokines levels in serum increased after Freund's complete adjuvant-emulsified BSA administration, as compared to control. The serum corticosterone and serum cytokine profile were also elevated. Results suggested that soluble protein antigen (BSA) administration stimulated steroidogenesis in murine lymphoid tissues and rise in the pro-inflammatory or inflammatory cytokine levels might indicate monocyte recruitment as well as TH1 activation.

Ginkgo biloba extract enhances testosterone synthesis of Leydig cells in type 2 diabetic rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Ginkgo biloba extract (EGB) on the testosterone synthesis in the Leydig cells of type 2 diabetic rats.</p><p><b>METHODS</b>Thirty male SD rats were equally randomised into a normal control, a type 2 diabetic and an EGB group. Morphological changes of Leydig cells were observed by light microscopy (LM) and transmission electron microscopy (TEM), concentrations of serum luteinizing hormone (LH) and testosterone (T) were determined by enzyme linked immunosorbent assay (ELISA), and the mRNA levels in the steroidogenic acute regulatory protein (StAR), cytochrome P450 side chain cleavage (P450scc), cytochrome P450 17a-hydroxylase (P450c17), 17beta-hydroxysteroid dehydrogenase 3 (17beta-HSD3) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD1) from the Leydig cells were examined by RT-PCR.</p><p><b>RESULTS</b>Compared with the normal control, there was a significant decrease in the number and volume of Leydig cells, the levels of serum LH and T and the expression of mRNA in StAR, P450scc, 17beta-HSD3 and 3beta-HSD1 in the type 2 diabetes group. And the expression of the P450c17 gene showed a tendency of descending, but with no significance. Compared with the type 2 diabetes group, 12 weeks of EGB treatment caused very slight pathological changes in the Leydig cells, significantly increased the concentrations of blood LH and T, markedly elevated the levels of mRNA in StAR and P450scc and induced an ascending tendency of the expressions of P450c17, 17beta-HSD3 and 3beta-HSD1.</p><p><b>CONCLUSION</b>EGB enhances testosterone synthesis and secretion of Leydig cells by reducing the impairment of the testis in type 2 diabetic rats.</p>

Study on inhibitory effect of medicated serum of SLW on estrogen production by human endometrial cells of endometriosis / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the mechanism of inhibitory effect of SLW on estrogen production by endometrial cells of endometriosis.</p><p><b>METHOD</b>After the model of eutopic primary cultured endometrial cells of endometiosis and hysteromyoma in vitro was successfully established, the changes of steroidgenic factor-1 (SF-1), chicken ovalbumin upstream-transcription factor (COUP-TF), 17-beta-hydroxysteroid dehydrogenase 1 (17-beta-HSD1) and 17-beta-hydroxysteroid dehydrogenase 2 (17-beta-HSD2) mRNA were detected by RT-PCR before and after treatment of medicated serum of SLW. The changes of SF-1 and COUP-TF protein were also observed by western blot synchronously according to the same treatment method mentioned-above. Meanwhile ,the data of hysteromyoma group was obtained from the above experiments.</p><p><b>RESULT</b>The expression of SF-1 mRNA and protein, 17-beta-HSD1 mRNA was weak, but COUP-TF mRNA and protein, 17-beta-HSD2 mRNA was remarkable in Hysteromyoma endometrium, as compared with those of endometiosis ,which was taken as control group (P<0.01). After the 48 hours' treatment of medicated serum of 5.0, 2.5 g kg(-1) d(-1) of SLW , the expression of COUP-TF mRNA and protein, 17beta-HSD2 mRNA was found significantly increased, but SF-1 mRNA and protein, 17-beta-HSD 1 mRNA was decreased in contrast to the control group (P <0.01 or P <0.05). Although the expresson of COUP-TF mRNA and protein was increased, SF-1 protein and 17-beta-HSD1 mRNA was decreased in 1.25 g kg(-1) d(-1) medicated serum group ,compared with those of the control group (P <0.01), the low dose group had no apparent inhibitory effect on the expression of SF-1, 17-beta-HSD2 mRNA.</p><p><b>CONCLUSION</b>The medicated serum of SLW could inhibit the secretion of estradiol in eutopic endometrial cells of endometiosis, and its mechanism might be associated with combined action of inhibiting expression of SF-1, 17-beta-HSD1 and up-regulating expression of COUP-TF, 17-beta-HSD2.</p>

Effects of infrasound on activities of 3beta hydroxysteroid dehydrogenase and acid phosphatase of polygonal cells in adrenal cortex zona fasciculate in mice / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the biological effects of infrasound on the polygonal cells in adrenal cortex zona fasciculation in mice.</p><p><b>METHODS</b>The biological effects of infrasound on the activities of 3beta hydroxysteroid dehydrogenase (3-betaHSDH) and acid phosphatase(ACP) of the polygonal cells in adrenal cortex zona fasciculate were observed when exposure to 8 and 16 Hz infrasound at 80, 90, 100, 110, 120 and 130 dB for 1 day, 7 days and 14 days or 14 days after the exposure.</p><p><b>RESULTS</b>When exposure to 8 Hz infrasound, the enzyme activities of 3-betaHSDH increase as the sound pressure levels increase. Only when the sound pressure levels reach 130 dB, the enzyme activities began to decrease exceptionally. When exposure to 16 Hz, 80 dB infrasound, no significant difference between the treatment and control group in the activities of 3-betaHSDH could be observed, but the injury of the polygonal cells had appeared. When exposure to 16 Hz, 100 dB infrasound, the activities of 3-betaHSDH started to increase. The cell injury still existed. When exposed to 16 Hz, 120 dB infrasound, the local tissue damage represented. Fourteen days after the mice exposure to 8 Hz, 90 dB and 130 dB infrasound for 14 days continuously, the local tissue injury of the adrenal cortex zona fasciculation began to recover at certain extent, but the higher the exposure sound pressure level, the poorer the tissue recovery.</p><p><b>CONCLUSION</b>The biological effects of infrasound on the polygonal cells in adrenal cortex zona fasciculation response to the frequency of the infrasound are found at certain action strength range, but this characteristic usually is covered by the severe tissue injury. When exposure to infrasound is stopped for a period of time, the local tissue injury of the adrenal cortex zona fasciculation could recovers at certain extent, but the higher the exposure sound pressure level, the more poorer the tissue recovery.</p>

Effect of exogenous selenium on the testicular toxicity induced by ethanol in rats.

The effects of supplementation of selenium at a dose of 10 microg/ kg body weight were investigated on ethanol induced testicular toxicity in rats. In the present study, four groups of male albino rats were maintained for 60 days, as follows: (1) Control group (normal diet) (2) Ethanol group (4g/kg body weight) (3) Selenium (10 microg/kg body weight) (4) Ethanol + Selenium (4g/kg body weight + 10 microg/kg body weight). Results revealed that ethanol intake caused drastic changes in the sperm count, sperm motility and sperm morphology. It also reduced the levels of testosterone and fructose. The activities of 3betaHSD, 17betaHSD in the testis and SDH in the seminal plasma were also reduced. Lipid peroxidation was also enhanced as the lipid peroxidation products were increased and the activities of the scavenging enzymes were reduced. But on coadministration of selenium along with alcohol all the biochemical parameters were altered to near normal levels indicating a protective effect of selenium. These results were reinforced by the histopathological studies.

Hormonal contraceptive like effect of estrogen in milk protein-fed male rats.

Adult male rats received daily injections (sc) of estradiol-17 beta (50 microg/100 g body wt per day) for 7 days. When they were sacrificed 14 days after the last injection, serum levels of gonadotropins and testosterone and weights of accessory sex organs were decreased significantly, testicular 17-hydroxysteroid dehydroganase activity was suppressed and spermatogenesis was inhibited in 5.0% casein-fed estrogen-treated rats. Feeding of 20.0% casein diet to estrogen-treated rats resulted in increased serum concentration of gonadotropins and testosterone. LH and testosterone appeared to be normal in 20.0% casein-fed estrogen-treated rats while serum FSH levels remained subnormal. The estrogen-treated rats fed on 20.0% casein diet showed decreased spermatogenesis in comparison with control rats fed on 20.0% casein diet. Together, these results indicate that high casein diet stimulates synthesis of testicular testosterone and increases serum LH levels more than FSH in estrogen-treated rats. It is concluded that estrogen in the presence of high milk protein diet may be considered to be a suitable steroid hormone in the development of a male contraceptive.

Dose-dependent effect of copper chloride on male reproductive function in immature rats.

BACKGROUND: Copper is essential as a trace element for metabolic processes. Exposure to copper in industries develops toxicity among the workers. Previous findings on adverse effects of copper on male reproductive function in adult albino rats led to investigate the effects of this metal on reproductive function of maturing male rats in the present experiment. METHODOLOGY: To study these effects, immature (30 to 35 days old) Wistar strain albino rats weighing about 50-60 g were treated intraperitoneally with copper chloride at doses of 1000, 2000 and 3000 microg/kg body weight/day for 26 days. RESULT: Significant fall in accessory sex organ weight and inhibition of testicular 17beta-hydroxysteroid dehydrogenase activity along with degeneration of testicular growing spermatogenic cells and reduction in serum testosterone, FSH and LH level were observed at the doses of 2000 and 3000microg/kg/day. On the other hand, at the dose of 1000 microg/kg/day significant increase in testicular steroidogenic enzyme activity and stimulation of testicular spermatogenesis along with rise in serum testosterone and LH level were observed, though no significant change was observed in serum FSH level. This suggests that copper has got a dose-dependent effect on testicular steroidogenesis and spermatogenesis and serum testosterone and LH level in maturing male rats.

Effect of chronic ethanol administration on testicular antioxidant system and steroidogenic enzyme activity in rats.

In order to find out the effect of chronic ethanol administration on testicular antioxidant system and steroidogenic enzyme activity, male rats fed with ethanol 1.6g/kg body weight per day for four weeks were studied. Besides a drastic reduction in body and testis weight, there was decrease in ascorbic acid, reduced glutathione and activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase in the testicular tissue of the treated animals. Simultaneously, there was increase in lipid peroxidation and glutathione S-transferase activity. Activities of 3 beta-hydroxy steroid dehydrogenase and 17 beta-hydroxy steroid dehydrogenase were also found decreased in the treated animals. The results indicate that chronic ethanol administration resulted in increase in oxidative stress and decrease in the activities of steroidogenic enzymes in the rat testes.

Altered expression of the HSD17B4 gene in esophageal squamous cell carcinoma and loss of heterozygosity analysis / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the alteration of the gene HSD17B4 in esophageal squamous cell carcinoma and its potential significance.</p><p><b>METHODS</b>The mRNA expression and loss of heterozygosity (LOH) of HSD17B4 in 40 primary esophageal tumors were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and microsatellite analysis with the intragenic marker D5S1384 of the gene.</p><p><b>RESULTS</b>The frequencies of allelic loss of D5S1384 and the rate of down-regulation of gene HSD17B4 were 46.2% and 62.5%, respectively.</p><p><b>CONCLUSION</b>HSD17B4 may be a candidate tumor suppressor gene associated with esophageal squamous cell carcinoma.</p>

Relationship between the increase of hepatic D-bifunctional protein activity and bile acid biosynthesis in rats / 中国医学科学院学报

<p><b>OBJECTIVE</b>To determine the physiological role of D-bifunctional protein (DBP) in bile acid biosynthesis through investigating the effect of increasing activity of DBP on bile acid biosynthesis.</p><p><b>METHODS</b>Twenty male Wistar rats were divided into two groups: diethylhexyl phthalate (DEHP) group (n = 10) and control group (n = 10). Serum triglyceride, total cholesterol, hepatic DBP activity, and fecal bile acids were assayed. The mRNA levels of hepatic peroxisome proliferator-activated receptor alpha (PPARalpha), DBP, and cholesterol 7alpha-hydroxylase (CYP7A1) were detected by RT-PCR.</p><p><b>RESULTS</b>Compared with control group, serum triglyceride level was decreased significantly and PPARalphamRNA level was increased significantly in DEHP group (P < 0.01). Together with a sharp induction of DBP mRNA expression and DBP activity in DEHP group (P < 0.01), the levels of CYP7A1 mRNA and fecal bile acids were significantly increased by 1.9 times and 1.6 times respectively compared to control group (P < 0.01). There was a significantly positive correlation between DBP mRNA level or DBP activity and CYP7A1 mRNA level (r = 0.89, P < 0.01; r = 0.95, P < 0.01).</p><p><b>CONCLUSION</b>The up-regulation of DBP mRNA and activity in liver can result in the increase in CYP7A1 mRNA expression and bile acid biosynthesis, suggesting that DBP may be involved in bile acid biosynthesis together with CYP7A1.</p>

Moduladores seletivos de enzimas estrogênicas - ações na mama / Selective estrogen enzyme modulators - actions on breast

O Tecido mamário canceroso contém todas as enzimas (estrona sulfatase, 17beta-hidroxiesteróide desidrogenase, aromatase) envolvidas nos últimos passos da biossíntese do estradiol. Este tecido também contém sulfotransferase para a formação de sulfatos de estrogênio biologicamente inativos. Nos últimos anos, demonstrou-se que vários progestágenos (promegestona, acetato de nomegestrol, medrogestona), bem como a tibolona e seus metabólitos são potentes inibidores das atividades da sulfatase e da 17beta-hidroxiesteróide desidrogenase. Mostrou-se, também, que promegestona, acetato de nomegestrol, medrogestona ou tibolona podem estimular a atividade da sulfotransferase para a produção local de sulfatos de estrogênio. Todos estes dados, em adição a numerosos agentes que podem bloquear a ação da aromatase, levam ao novo conceito dos moduladores seletivos de enzimas estrogênicas (SEEM), o qual pode ser amplamente aplicado ao tecido mamário canceroso. A exploração de vários progestágenos e outros agentes ativos em trials com pacientes com câncer de mama, mostrando efeito inibidor na sulfatase e 17 beta-hidroxiesteróide desidrogenase, ou efeito estimulador na sulfotransferase, irá proporcionar nova possibilidade no tratamento desta doença

Effect of mercuric chloride on testicular activities in mice, Musculus albinus.

Impaired testicular function was observed after an exposure of Swiss albino mice (30 +/- 2 g) to mercuric chloride. A sublethal chronic exposure (0.5 ppm for 21 days) resulted in regressed histological and histochemical properties of the testis. The changes observed were degenerated tunica albuginea, abnormal configurations of seminiferous tubules, deformed primary and secondary spermatocytes, hypertrophy and vacuolization in interstitial cells and Sertoli cells. The 3 beta and 17 beta hydroxy steroid dehydrogenase enzyme and the level of testosterone hormone were significantly (p < 0.001) reduced. The diameter of different spermatogenic cells were significantly (p < 0.001) reduced.