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Query: UNIPROT:P06889 (Mol)
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Previous in vitro experiments showed that both, Taenia crassiceps and Taenia solium cysticerci have the ability to metabolize exogenous androstenedione to testosterone. Here we evaluate on the capacity of both cysticerci to synthesize several sex steroid hormones, using different hormonal precursors. Experiments using thin layer chromatography (TLC) showed that both cysticerci were able to produce (3)H-hydroxyprogesterone, (3)H-androstenedione and (3)H-testosterone when (3)H-progesterone was used as the precursor. They also synthesized (3)H-androstenediol and (3)H-testosterone when (3)H-dehydroepiandrosterone was the precursor. In addition, both cysticerci interconverted (3)H-estradiol and (3)H-estrone. These results, strongly suggest the presence and activity of the Delta4 and Delta5 steroid pathway enzymes, 3beta-hydroxysteroid dehydrogenase/Delta(5-4) isomerase-like enzyme (3beta-HSD), that converts androstenediol into testosterone; and the 17beta-hydroxysteroid dehydrogenase that interconverts estradiol and estrone, in both types of cysticerci.
J Steroid Biochem Mol Biol 2006 Jun
PMID:Metabolism of steroid hormones by Taenia solium and Taenia crassiceps cysticerci. 1664 9

The objective of this study was to investigate the levels of expression of steroid biosynthetic enzymes and steroidogenic acute regulatory protein (StAR) at different stages of ovarian follicular development in zebrafish (Danio rerio), and to investigate the sites within the steroid biosynthetic pathway that may be regulated by gonadotropins. Ovarian follicles of sexually mature fish were separated into primary, previtellogenic, vitellogenic, and mature stages and the expression of StAR, P450 side chain cleavage (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), P450 hydroxylase/lyase (P450c17), 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), 17beta-hydroxysteroid dehydrogenase type 3 (17beta-HSD3), and P450 aromatase (P450aromA) was determined by Real time RT-PCR. The expression of all genes changed significantly as follicles grew, with a decrease in the expression of StAR, P450scc, 3beta-HSD and P450c17 with maturation, and an increase in the expression of 17beta-HSD3 during vitellogenesis and 17beta-HSD1 and P450aromA during previtellogenesis. In vitro incubation of vitellogenic follicles demonstrated that the expression of StAR, 17beta-HSD3, and P450aromA increased in response to hCG, and decreased in the absence of hCG. In contrast, the expression of P450scc, 3beta-HSD, P450c17, and 17beta-HSD1 remained constant between treatments and over time. Testosterone and estradiol production in the culture medium was stimulated by human chorionic gonadotropin (hCG). These experiments aid in the characterization of the roles and regulation of steroids throughout ovarian development, and suggest that gonadotropins play a key role in the regulation of StAR, 17beta-HSD3, and P450aromA in zebrafish.
Mol Reprod Dev 2006 Aug
PMID:Characterization of the mRNA expression of StAR and steroidogenic enzymes in zebrafish ovarian follicles. 1670 73

Mammalian 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD) is a member of the short chain dehydrogenase/reductase. It is a key steroidogenic enzyme that catalyzes the first step of the multienzyme pathway conversion of circulating dehydroepiandrosterone and pregnenolone to active steroid hormones. A three dimensional model of a ternary complex of human 3beta-HSD type 1 (3beta-HSD_1) with an NAD cofactor and androstenedione product has been developed based upon X-ray structures of the ternary complex of E. coli UDP-galactose 4-epimerase (UDPGE) with an NAD cofactor and substrate (PDB_AC: 1NAH) and the ternary complex of human type 1 17beta-hydroxysteroid dehydrogenase (17beta-HSD_1) with an NADP cofactor and androstenedione (PDB_AC: 1QYX). The dimeric structure of the enzyme was built from two monomer models of 3beta-HSD_1 by respective 3D superposition with A and B subunits of the dimeric structure of Streptococcus suis DTDP-D-glucose 4,6-dehydratase (PDB_AC: 1KEP). The 3D model structure of 3beta-HSD_1 has been successfully used for the rational design of mutagenic experiments to further elucidate the key substrate binding residues in the active site as well as the basis for dual function of the 3beta-HSD_1 enzyme. The structure based mutant enzymes, Asn100Ser, Asn100Ala, Glu126Leu, His232Ala, Ser322Ala and Asn323Leu, have been constructed and functionally characterized. The mutagenic experiments have confirmed the predicted roles of the His232 and Asn323 residues in recognition of the 17-keto group of the substrate and identified Asn100 and Glu126 residues as key residues that participate for the dehydrogenase and isomerization reactions, respectively.
J Steroid Biochem Mol Biol 2006 Sep
PMID:Rational proteomics V: structure-based mutagenesis has revealed key residues responsible for substrate recognition and catalysis by the dehydrogenase and isomerase activities in human 3beta-hydroxysteroid dehydrogenase/isomerase type 1. 1688 58

Therapies designed to treat hypercortisolism have usually sought to reduce circulating glucocorticoid concentrations, however the local tissue endocrine environment could be an alternative target. The 3beta-hydroxysteroid dehydrogenase Delta5-4 isomerase (3beta-HSD) inhibitor trilostane is of interest, since, although it is only moderately and transiently effective in reducing circulating steroid, it is remarkably effective in alleviating Cushing's symptoms in veterinary applications. To seek alternative modes of action, male Wistar rats were treated with trilostane. Although final circulating corticosteroid concentrations were unaffected, liver 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) transcription and translation was significantly increased, whereas 3beta-HSD was not affected either in liver or adrenal. Glucocorticoid receptor (GR) mRNA was down-regulated, and mineralocorticoid receptor (MR) up-regulated by trilostane treatment: no changes in 11beta-HSD1 mRNA were observed. Trilostane also had no direct effect on GR response element-mediated gene transcription. The results show that the tissue endocrine environment is affected by trilostane treatment in the absence of sustained changes in circulating corticosteroid. The combination of increased 11beta-HSD2 and reduced GR expression in target organs could be expected to ameliorate the effects of excess glucocorticoid, suggesting new therapeutic approaches.
J Steroid Biochem Mol Biol 2006 Oct
PMID:Regulation of hepatic steroid receptors and enzymes by the 3beta-hydroxysteroid dehydrogenase inhibitor trilostane. 1689 43

In postmenopausal women, tibolone shows clear tissue differences in its stimulatory effects on the vagina and uterus. In rats, however, it has stimulatory effects on both tissues, with a different, more estrogenic, effect on the uterus than in humans. This may be due to differences in local metabolism. Therefore, in the present study, the metabolism of tibolone was analyzed in incubations of uterine and vaginal tissue from postmenopausal women and ovariectomized rats using radiolabeled tibolone in order to understand the tissue- and species-specific metabolism. In the rat, tibolone (50 nM) was mainly 3alpha-reduced to the estrogenic 3alpha-OH-tibolone in the uterus and vagina. The 3beta-OH tibolone can be isomerized to 3alpha-OH-tibolone with tibolone as intermediate. In contrast, in the same tissues from postmenopausal women, the progestagenic Delta4-isomer and estrogenic 3beta-OH-tibolone were the major metabolites of tibolone. The formation of the Delta4-isomer was higher in uterine tissue. The 3beta-hydroxysteroid dehydrogenase (HSD) inhibitor epostane had no effect on tibolone metabolism in human uterine and vaginal tissue microsomes and HEK293 cells expressing the human 3beta-HSD types 1 and 2 isoforms did not metabolize tibolone. Moreover, the 3beta-reduction of tibolone to 3beta-OH-tibolone was NADPH dependent, while the isomerization of tibolone to the Delta4-isomer did not require a cofactor. It was therefore concluded that human 3beta-HSD isoforms are not involved in the metabolism of tibolone, and that the 3beta-reduction and the Delta5-10 to Delta4 isomerization may be catalyzed by different enzymes. In conclusion, we showed that, in hormone therapy target tissues of the rat as compared with the human, different metabolic pathways for tibolone exist and therefore result in metabolites with different pharmacological properties. The rat is therefore a poor model to predict the effects of tibolone on the uterus in postmenopausal women.
J Steroid Biochem Mol Biol 2006 Sep
PMID:Metabolism of tibolone and its metabolites in uterine and vaginal tissue of rat and human origin. 1689 45

The pregnane X receptor (PXR) was isolated as a xenobiotic receptor that regulates responses to various xenobiotic agents. In this study, we show that PXR plays an important endobiotic role in adrenal steroid homeostasis. Activation of PXR by genetic (transgene) or pharmacological (ligand, such as rifampicin) markedly increased plasma concentrations of corticosterone and aldosterone, the respective primary glucocorticoid and mineralocorticoid in rodents. The increased levels of corticosterone and aldosterone were associated with activation of adrenal steroidogenic enzymes, including cytochrome P450 (CYP)11a1, CYP11b1, CYP11b2, and 3beta-hydroxysteroid dehydrogenase. The PXR-activating transgenic mice also exhibited hypertrophy of the adrenal cortex, loss of glucocorticoid circadian rhythm, and lack of glucocorticoid responses to psychogenic stress. Interestingly, the transgenic mice had normal pituitary secretion of ACTH and the corticosterone-suppressing effect of dexamethasone was intact, suggesting a functional hypothalamus-pituitary-adrenal axis despite a severe disruption of adrenal steroid homeostasis. The ACTH-independent hypercortisolism in the PXR-activating transgenic mice is reminiscent of the pseudo-Cushing's syndrome in patients. The glucocorticoid effect appears to be PXR specific, as the activation of constitutive androstane receptor in transgenic mice had little effect. We propose that PXR is a potential endocrine disrupting factor that may have broad implications in steroid homeostasis and drug-hormone interactions.
Mol Endocrinol 2007 Jan
PMID:Activation of pregnane X receptor disrupts glucocorticoid and mineralocorticoid homeostasis. 1697 56

The interrenal gland (adrenocortical homolog) of elasmobranchs produces a unique steroid, 1alpha-hydroxycorticosterone (1alpha-B). The synthesis of this and most other steroids requires both cholesterol side chain cleavage (CYP11A) and 3beta-hydroxysteroid dehydrogenase (HSD3). To facilitate the study of elasmobranch steroidogenesis, we isolated complementary DNAs encoding CYP11A and HSD3 from the freshwater stingray Potamotrygon motoro. The P. motoro CYP11A (2182 bp total length) and HSD3 (2248 bp total length) cDNAs harbor open reading frames that encode proteins of 542 and 376 amino acids (respectively) that are similar (CYP11A: 39-61% identical; HSD3: 36-53% identical) to their homologs from other vertebrates. In molecular phylogenetic analysis, P. motoro CYP11A segregates with CYP11A proteins (and not with related CYP11B proteins) and P. motoro HSD3 segregates with steroidogenic HSD3 proteins from other fishes. CYP11A and HSD3 mRNA is found only in interrenal and gonadal tissues, indicating de novo steroidogenesis is restricted to these tissues. Because 1alpha-B is thought to act in the elasmobranch response to hydromineral disturbances, we examined the effect of adapting P. motoro to 10 ppt seawater on mRNAs encoding steroidogenic genes. The P. motoro response to this salinity challenge does not include interrenal hypertrophy or an increase in the levels of interrenal CYP11A, HSD3 or steroidogenic acute regulatory protein (StAR) mRNA. This study is the first to isolate full length cDNAs encoding elasmobranch CYP11A and HSD3 and the first to examine the regulation of steroidogenic genes in elasmobranch interrenal cells.
Comp Biochem Physiol B Biochem Mol Biol
PMID:Characterization of cDNAs encoding cholesterol side chain cleavage and 3beta-hydroxysteroid dehydrogenase in the freshwater stingray Potamotrygon motoro. 1697 95

Calcitriol exerts a diverse range of biological actions including the control of growth and cell differentiation, modulation of hormone secretion, and regulation of reproductive function. The placenta synthesizes calcitriol through the expression of CYP27B1, but little is known about local actions of this hormone in the fetoplacental unit. The objective of this study was to investigate the effects of calcitriol upon progesterone (P(4)) and estradiol (E(2)) secretion in trophoblasts cultured from term human placenta. Cells were incubated in the presence of calcitriol for 18 h and pregnenolone or androstenedione were subsequently added as substrates for the 3beta-hydroxysteroid dehydrogenase (3beta-HSD) or P450-aromatase (CYP19), respectively. Calcitriol stimulated in a dose-dependent manner E(2) and P(4) secretion. The use of a selective inhibitor of PKA prevented the effects of calcitriol upon E(2) secretion, but not on P(4). These results show that calcitriol is a physiological regulator of placental E(2) and P(4) production and suggest a novel role for calcitriol upon placental steroidogenesis.
J Steroid Biochem Mol Biol 2007 Mar
PMID:Estradiol and progesterone synthesis in human placenta is stimulated by calcitriol. 1725 26

In this study, we examine the possible contribution of the seminal vesicles of the male round goby to the production of putative steroidal pheromones. A previous study showed that the testes of the round goby are rich in steroid-producing Leydig-like cells; and when incubated in vitro, convert tritiated androstenedione to at least six other steroids, including one not previously identified in fish--namely 3alpha-hydroxy-5beta-androstane-11,17-dione (11-oxo-etiocholanolone, 11-oxo-ETIO). The seminal vesicles of reproductively mature males were examined by conventional histology, transmission electron microscopy and immunocytochemistry (utilizing an antibody against 3beta-hydroxysteroid dehydrogenase--a key enzyme in vertebrate steroid synthesis). All three procedures identified Leydig cells in the proximal and medial regions of the seminal vesicles. In vitro incubation of seminal vesicles with tritiated androstenedione demonstrated biosynthesis of 11-oxo-androstenedione, 11-oxo-testosterone (more commonly known as 11-ketotestosterone) and 11 oxo-ETIO. These data indicate that the seminal vesicles, as well as the testes are involved in the synthesis of steroidal compounds that may function as pheromones.
Comp Biochem Physiol A Mol Integr Physiol 2007 Sep
PMID:The seminal vesicle synthesizes steroids in the round goby Neogobius melanostomus. 1751 68

Using polyclonal antibodies, we examined the localization of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) as markers of the site of steroidogenetic activity during the spermatogenesis of Torpedo marmorata. These enzymes play a central role in the biosynthesis of steroid hormones, including androgen and oestrogen production. We demonstrated that in the spotted ray testis, Sertoli and Leydig cells, as well as spermatogonia, show a positive reaction to anti 3beta-HSD and 17beta-HSD antibodies. In particular, we demonstrated that Sertoli cells show a positive reaction to anti 3beta-HSD and 17beta-HSD antibodies in cysts containing spermatogonia and spermatozoa, while Leydig cells present a positive reaction only when they are located between cysts containing meiotic cells. This study strongly suggests that, as hypothesised in our previous study [Prisco, M., Liguoro, A., D'Onghia, B., Ricchiari, L., Andreuccetti, P., Angelini, F., 2002. Fine structure of Leydig and Sertoli cells in the testis of immature and mature spotted ray Torpedo marmorata. Mol. Reprod. Dev. 63, 192-201.], Sertoli and Leydig cells are differently involved in the hormonal control of spermatogenesis: Sertoli cells before the beginning of meiosis and after spermiation, Leydig cells only during meiosis phase. Moreover, the present paper deals with the possibility that also spermatogonia are engaged in the production of androgen hormones, as they are characterized by the presence of 3beta-HSD and 17beta-HSD enzymes, and show the ultrastructural features of steroid hormone-producing cells.
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PMID:Immunolocalization of 3beta-HSD and 17beta-HSD in the testis of the spotted ray Torpedo marmorata. 1756 Oct 19


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