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At least 325 records · Page 18Linked to original sources
PubMed2002

Expression of key enzymes in bile acid biosynthesis during development: CYP7B1-mediated activities show tissue-specific differences.

The developmental variation of cytochrome P450 (CYP)7A1, CYP7B1, CYP27A1, and 3beta-hydroxy-Delta(5)-C(27)-steroid dehydrogenase, key enzymes in bile acid biosynthesis, were investigated in pigs of different ages. As part of these studies, peptide sequences from a purified pig liver oxysterol 7alpha-hydroxylase were analyzed. The sequences showed a high degree of identity with those of murine and human CYP7B1. Enzymatic activities and mRNA levels of CYP27A1 and 3beta-hydroxy-Delta(5)-C(27)-steroid dehydrogenase were similar in livers of newborn and 6-month-old pigs. Enzymatic activity mediated by CYP7A1 increased several-fold between infancy and adolescence. Hepatic CYP7A1 and CYP7B1 mRNA levels increased several-fold with age. Hepatic microsomal 7alpha-hydroxylation of 27-hydroxycholesterol and dehydroepiandrosterone, substrates typical for CYP7B1, increased about 5-fold between infancy and adolescence whereas the activities in kidney microsomes decreased at least 10-fold. In conclusion, the results indicate that the expression of CYP27A1 and 3beta-hydroxy-Delta(5)-C(27)-steroid dehydrogenase are similar in livers of newborn and 6-month-old pigs whereas the levels of CYP7A1 increase. The finding that the levels of CYP7B1 increase with age in the liver but decrease in the kidney suggest a tissue-specific developmental regulation of CYP7B1. The age-dependent variation in the liver and kidney suggests that hormonal factors are involved in the regulation of CYP7B1.

Aging↗
PubMed2002

[Enzyme inhibition in the drug therapy of benign prostatic hyperplasia].

Enzyme inhibition belongs to common mechanisms of drug action and enzymes of hormone metabolism belong to targets in the treatment of benign prostatic hyperplasia. Transformation of testosterone to 5 alpha-dihydrotestosterone is catalyzed by cholestenone-5 alpha-reductase (EC 1.3.1.22, 5 alpha-reductase). Different effects of dihydrotestosterone and testosterone represent a rational basis for pharmacotherapy by 5 alpha-reductase inhibition. The enzyme is active in the prostate and other organs and tissues, with different distribution of at least two 5 alpha-reductase isoenzymes. Beside this, progesterone-5 alpha-reductase (EC 1.3.1.30) as another enzyme with 5 alpha-reductase activity is present in human tissues including the prostate. The existence of several 5 alpha-reductase activities gives bright possibilities of 5 alpha-reductase inhibition. Basic 5 alpha-reductase inhibitors are synthetic steroid (e.g. finasteride--Proscar). Various mechanisms of their effect (classical reversible competitive inhibition, mechanism-based "suicide" inhibitors, tightly bound irreversible inhibitors...) represent different pharmacokinetic patterns, too. Non-steroidal 5 alpha-reductase inhibitors (e.g. polyunsaturated fatty acids) are effective components of several phytopharmaceuticals. They receive attention due to their complexity and low hazards. Extracts of Serenoa repens seeds (Permixon, Capistan in the Czech Republic), of Pygeum africanum, of Urtica radicis roots (Urtica, Urtiron) or catequine structures from the green tea belong to this group. Beside androgens, participation of estrogens in the origin and development of benign prostatic hyperplasia is probable. Inhibition of the "aromatase" complex, which catalyzes transformation of androgens to estrogens, may contribute to the complexity of phytotherapeutic effects.

Cholestenone 5 alpha-Reductase↗
PubMed1992

[The effect of chemical damage to the adrenal cortex on its ontogenetic development].

We studied adrenal gland of rats at the age of 1 month, which underwent injections of dioxin-preparations during a week. In 1, 6, 12 days; 1, 3, 5, 5, 7, 13 months adrenal gland mass, adrenal cortex size, adrenocorticocytes number, 3B-ol-steroid dehydrogenase and succinate dehydrogenase activities of the experimental animals differed greatly from that of the control. It was found that chemical damage of the gland at an early stage changes it greatly during the following ontogenic development.

Adrenal Cortex↗
PubMed1977

Enzyme histochemistry of ovarina lipoid cell hyperplasia in a masculinized patient.

In an effort to better identify the specific steroids produced by histologically similar cells of certain ovarian tumors, a battery of histochemical assays was performed on a masculinizing tumor removed from a 21-year-old patient. Certain reactions were distinguished that seemed to be specific for the histologically classic luteinized stromal cell, and these reactions can be correlated with those obtained with Leydig and hilar cells. The apparent precursors of the interstitial cells (ISC) of this tumor, and to a lesser extent the immature ISC, possess unusually high cholinesterase activity, especially with the butyryl ester. The importance of the perivascular and neural elements in the process of steroidogenesis is suggested by the findings in this case.

Adenosine Triphosphatases↗
PubMedDate not supplied

Evidence that testosterone regulates Leydig cell 3 beta-hydroxysteroid dehydrogenase-isomerase activity by a trans-acting factor distal to the androgen receptor.

Leydig cells are a target for their own steroid product, testosterone, and thus could be subject to short-loop feedback regulation by androgens. The authors previously reported that 3 beta-hydroxysteroid dehydrogenase-isomerase (3 beta HSD) activity was higher in freshly isolated Leydig cells from C57BL/6J than those from C3H/HeJ inbred mice. To determine whether this strain-related difference in 3 beta HSD activity could be mediated by differential sensitivity to feedback effects of testosterone, Leydig cells from the two strains were cultured in the presence or absence of testosterone, the synthetic androgen receptor agonist, mibolerone, or the nonaromatizable androgen, dihydrotestosterone. After 7 days of treatment, all three androgens significantly decreased 3 beta HSD activity in Leydig cells from C57BL/6J, but not from C3H/HeJ mice. When Leydig cells were cultured with hydroxyflutamide, an androgen receptor antagonist, the effect of testosterone was negated. To determine whether the strain-related difference in sensitivity to testosterone was mediated by a difference in the androgen receptor protein, Leydig cells from reciprocal F1 hybrid lines of mice were cultured in the presence or absence of testosterone. Testosterone treatment inhibited 3 beta HSD activity in both F1 lines to the same extent as observed for Leydig cells from C57BL/6J mice. Thus, there is a strain-related difference in the response to testosterone, but it cannot account for the strain-related difference in Leydig cell 3 beta HSD activity because the high 3 beta HSD strain (C57BL/6J) is the sensitive strain. Although the effect on C57BL/6J Leydig cells is androgen receptor-mediated, the dominant effect of testosterone on both F1 lines rules out a difference in the androgen receptor protein per se. However, the data are consistent with the difference being in a trans-acting factor distal to the androgen receptor.

Androgen Receptor Antagonists↗
PubMed1992

Effect of certain toxicants on gonadotropin-induced ovarian non-esterified cholesterol depletion and steroidogenic enzyme stimulation of the common carp Cyprinus carpio in vitro.

Isolated ovarian tissues from the common carp, Cyprinus carpio were incubated in vitro to obtain a discrete effect of four common toxicants of industrial origin, namely phenol, sulfide, mercuric chloride and cadmium chloride, on gonadotropin-induced alteration of nonesterified and esterified cholesterol and steroidogenic enzymes, delta 5-3 beta-HSD and 17 beta-HSD activity. Stage II ovarian tissue containing 30-40% mature oocytes were shown to be most responsive to gonadotropins in depleting only nonesterified cholesterol moiety and stimulating the activity of both. Safe doses of above mentioned toxicants when added separately to stage II ovarian tissue with oLH (1 microgram/incubation) gonadotropin-induced depletion of nonesterified cholesterol and gonadotropin-induced stimulation of the activity of both enzymes was significantly inhibited. Esterified cholesterol remained almost unaltered. Findings clearly indicate the impairment of gonadotropin induced fish ovarian steroidogenesis by the four toxicants separately.

17-Hydroxysteroid Dehydrogenases↗
PubMed1991

Characterization of the structure-activity relationships of rat types I and II 3 beta-hydroxysteroid dehydrogenase/delta 5 -delta 4 isomerase by site-directed mutagenesis and expression in HeLa cells.

The membrane-bound enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5 -delta 4 isomerase (3 beta-HSD) catalyzes the conversion of delta 5 -3 beta-hydroxysteroid precursors into delta 4-ketosteroids, thus representing an essential step in the biosynthesis of all classes of hormonal steroids. We have recently characterized two types of cDNA clones encoding rat 3 beta-HSD proteins, the rat type I protein being much more active than type II. In order to characterize further the functional difference between these two 3 beta-HSD types, transient expression of type I and type II 3 beta-HSD cDNAs was performed in HeLa human cervical carcinoma cells. The present study demonstrates that the type I 3 beta-HSD protein has a relative specificity 64- and 46-fold higher than type II protein for pregnenolone (PREG) and dehydroepiandrosterone (DHEA) as substrates, respectively. The Km values of type I and type II enzymes were calculated at 0.74 and 14.3 microM, respectively, using PREG as substrate whereas the respective Km values were 0.68 and 12.9 microM when DHEA was used, thus showing that their different relative specificity results largely from a different affinity for substrates. Since the change of 4 amino acid residues in type II could prevent the formation of a putative membrane-spanning domain (MSD) predicted between amino acid residues 75 and 91, chimeric cDNAs containing either type I MSD in type II (II + MSD) or an absence of this MSD in type I (I-MSD) were constructed and transiently expressed. The addition of MSD intype II 3 beta-HSD markedly increased the affinity leading to Km values similar to those found in type I 3 beta-HSD, namely 0.36 and 0.40 microM for PREG and DHEA, respectively. II + MSD chimera thus encodes a protein having a relative specificity for PREG and DHEA of 58 and 73%, respectively, to that of native type I 3 beta-HSD. Moreover, removal of MSD in the type I protein (I-MSD chimera) decreased the relative specificity of type I 3 beta-HSD protein for PREG and DHEA to only 0.37 and 0.48%, with respective Km values of 11.7 and 11.0 microM, thus strongly indicating the functional importance of this putative MSD which is predicted in wild type rat type I as well as in macaque and human 3 beta-HSD proteins.

Amino Acid Sequence↗
PubMedDate not supplied

Ontogeny of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) in human testis as studied by immunocytochemistry.

The enzyme complex 3 beta-hydroxy-5-ene-steroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) is involved in the biosynthesis of all classes of active steroids, including androgens. To correlate possible changes in 3 beta-HSD with the well-known variations in testosterone secretion during development, the authors localized this enzyme by immunocytochemistry during fetal and postnatal periods of development in the human testis. In the fetal testis, 3 beta-HSD was detected in Leydig cells during the second and third trimester of gestation. In 8-month-old and 11-year-old boys, however, no immunoreaction could be detected in the testis. In pubertal boys, Leydig cells appeared well developed and immunopositive. Since the fluctuations in 3 beta-HSD immunoreactivity are similar to those already observed for androgen secretion, activation of 3 beta-HSD by trophic hormones may play an important role in androgen production during fetal and postnatal development.

Adolescent↗
PubMed1991

Characterization of rat 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase cDNAs and differential tissue-specific expression of the corresponding mRNAs in steroidogenic and peripheral tissues.

The conversion of 3 beta-hydroxy-5-ene steroids by the enzyme complex 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) is an essential step in the biosynthesis of all classes of hormonal steroids. We report the characterization of two types of cDNA clones encoding rat 3 beta-HSD isolated from a rat ovary lambda gt11 cDNA library with a human 3 beta-HSD cDNA probe. Both type I and type II cDNAs encode proteins of 372 amino acids having 94% homology. Transient expression of the type I and the type II 3 beta-HSD cDNAs in HeLa human cervical carcinoma cells reveals that both proteins possess 3 beta-hydroxysteroid dehydrogenase as well as delta 5-delta 4 isomerase activities for both delta 5-pregnene and delta 5-androstene precursors, although the type I 3 beta-HSD protein is more active than the type II. RNA blot analysis using type I 3 beta-HSD cDNA identifies major mRNA transcripts of 1.7 kilobase in rat ovary, testis, and adrenal poly(A)+ RNA. RNase protection assay using type I- and type II-specific cRNA probes revealed the existence of the two corresponding mRNAs in male and female rat adrenals and gonads as well as in female adipose tissue while only type I mRNA is present in male and female kidney. Moreover, in situ hybridization performed using type-specific labeled 24-mer oligonucleotides confirms that type I is the major mRNA species in the ovary and further indicates that both mRNA species have a similar cellular distribution in the ovarian tissue with the highest level of expression found in corpora lutea. Immunoblot analysis using polyclonal antibodies raised against purified human placental 3 beta-HSD identified a single 42-kDa band in rat ovary, testis, and adrenal, which agrees with the calculated molecular masses of 41,911 and 42,150 daltons for the type I and II proteins, respectively. Determination of 3 beta-HSD enzymatic activity using [14C]pregnenolone and [14C]dehydroepiandrosterone as substrates shows that 3 beta-HSD activity is present not only in the gonads and adrenals of animals of both sexes, but also in many peripheral tissues including adipose tissue, mammary gland, kidney, liver, prostate, seminal vesicle, uterus, skin, brain, heart, thymus, pancreas, lung, and spleen. The present data indicate the existence of two mRNAs encoding rat 3 beta-HSD and their differential tissular distribution in both steroidogenic and peripheral tissues.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗