METABOLISM OF ANDROGENS IN VITRO BY HUMAN FACIAL AND AXILLARY SKIN

1973 ◽  
Vol 59 (3) ◽  
pp. 475-486 ◽  
Author(s):  
J. B. HAY ◽  
M. B. HODGINS
Keyword(s):  
Human Skin ◽  
Enzyme Activities ◽  
Hydroxysteroid Dehydrogenase ◽  
Facial Skin ◽  
Steroid Hydroxylase ◽  
Skin Formation

SUMMARY Human skin from forehead, cheek and axilla was incubated in vitro with [7α-3H]dehydroepiandrosterone (DHA), [7α-3H]DHA sulphate, [7α-3H]-androstenedione and [7α-3H]testosterone. The following enzyme activities were detected: 3β-hydroxysteroid dehydrogenase Δ4-5 isomerase, 17β-hydroxysteroid dehydrogenase, 3β-hydroxysteroid dehydrogenase, 3α-hydroxysteroid dehydrogenase, 5α-reductase, 5β-reductase, sulphotransferase, sulphatase, steroid hydroxylase. 5α-Reduced steroids were the major metabolites. All four substrates were converted to 5α-dihydrotestosterone and 5α-androstane-3α,17β-diol. In axillary skin, conversion of 17-oxosteroids to 17β-hydroxysteroids was favoured, 5α-dihydrotestosterone and 5α-androstane-3α,17β-diol being major metabolites. In facial skin, formation of 17-oxosteroids predominated with little accumulation of 5α-dihydrotestosterone or 5α-androstane-3α,17β-diol. 5α-Androstane-3β,17β-diol was a metabolite of DHA, androstenedione and testosterone but was found in lower amounts than 5α-androstane-3α,17β-diol. Similarly conversions to epiandrosterone were much lower than to androsterone in all the skin specimens. It was concluded that the differences in accumulation of 5α-dihydrotestosterone were determined by the differences in 17β-oxidoreduction rather than differences in 5α-reductase, the activity of which was high in all skin specimens.

scholarly journals Inactivation of glucocorticoids by 11β-hydroxysteroid dehydrogenase enzymes increases during the meiotic maturation of porcine oocytes

Reproduction ◽  
2008 ◽  
Vol 136 (6) ◽  
pp. 725-732 ◽  
Author(s):  
Rachel J Webb ◽  
Neera Sunak ◽  
Lisa Wren ◽  
Anthony E Michael
Keyword(s):  
Oocyte Maturation ◽  
Enzyme Activities ◽  
Germinal Vesicle ◽  
Hydroxysteroid Dehydrogenase ◽  
Target Cells ◽  
Cortisol Metabolism ◽  
Enzymatic Inactivation ◽  
Glucocorticoid Metabolism ◽  
Ovarian Cyst Fluid

Recent reports have shown that glucocorticoids can modulate oocyte maturation in both teleost fish and mammals. Within potential target cells, the actions of physiological glucocorticoids are modulated by 11β-hydroxysteroid dehydrogenase (HSD11B) isoenzymes that catalyse the interconversion of cortisol and cortisone. Hence, the objective of this study was to establish whether HSD11B enzymes mediate cortisol–cortisone metabolism in porcine oocytes and, if so, whether the rate of glucocorticoid metabolism changes during oocyte maturation. Enzyme activities were measured in cumulus–oocyte complexes (COCs) and denuded oocytes (DOs) using radiometric conversion assays. While COCs and DOs oxidised cortisol to inert cortisone, there was no detectable regeneration of cortisol from cortisone. The rate of cortisol oxidation was higher in expanded COCs than in compact COCs containing germinal vesicle (GV) stage oocytes (111±6 vs 2041±115 fmol cortisone/oocyte.24 h; P<0.001). Likewise, HSD11B activities were 17±1 fold higher in DOs from expanded COCs than in those from compact COCs (P<0.001). When GV stage oocytes were subject to a 48 h in vitro maturation protocol, the enzyme activities were significantly increased from 146±18 to 1857±276 fmol cortisone/oocyte.24 h in GV versus MII stage oocytes respectively (P<0.001). Cortisol metabolism was inhibited by established pharmacological inhibitors of HSD11B (glycyrrhetinic acid and carbenoxolone), and by porcine follicular and ovarian cyst fluid. We conclude that an HSD11B enzyme (or enzymes) functions within porcine oocytes to oxidise cortisol, and that this enzymatic inactivation of cortisol increases during oocyte maturation.

ANDROGEN METABOLISM IN THE VENTRAL SEBACEOUS GLAND PATCH OF THE MONGOLIAN GERBIL

1973 ◽  
Vol 59 (3) ◽  
pp. 487-493 ◽  
Author(s):  
M. B. HODGINS ◽  
J. B. HAY
Keyword(s):  
Mongolian Gerbil ◽  
Enzyme Activities ◽  
Sebaceous Gland ◽  
Hydroxysteroid Dehydrogenase ◽  
Rat Skin ◽  
Androgen Metabolism

SUMMARY The metabolism of [7α-3H]dehydroepiandrosterone (DHA), [7α-3H]-androstenedione and [7α-3H]testosterone was studied in the ventral sebaceous gland patch of the Mongolian gerbil in vitro. The main enzyme activities found were 17β-hydroxysteroid dehydrogenase, 5α-reductase, 17α-hydroxysteroid dehydrogenase, 3α-hydroxysteroid dehydrogenase, sulphotransferase and hydroxylase. The active androgen 5α-dihydrotestosterone was formed in appreciable amounts from both testosterone and androstenedione. The 17β-hydroxysteroid dehydrogenase actively formed both 17-oxo and 17β-hydroxysteroids in this tissue. The conversion of DHA to C4–5 unsaturated steroids and 5α-steroids was not observed presumably due to a lack of 3β-hydroxysteroid dehydrogenase Δ4–5isomerase. The metabolism was compared with that in human and rat skin and its significance discussed.

METABOLISM OF ANDROGENS IN VITRO BY HUMAN FOETAL SKIN

1976 ◽  
Vol 70 (3) ◽  
pp. 491-499 ◽  
Author(s):  
F. SHARP ◽  
J. B. HAY ◽  
M. B. HODGINS
Keyword(s):  
Gestational Age ◽  
Enzyme Activities ◽  
Histochemical Study ◽  
Reductase Activity ◽  
Hydroxysteroid Dehydrogenase ◽  
Sebaceous Glands ◽  
Isomerase Activity ◽  
Human Foetuses

SUMMARY Fresh scalp, genital, chest and axillary skin from human foetuses of 12–41 weeks' maturity was incubated in Krebs' improved Ringer I medium with [7α-3H]dehydroepiandrosterone, [7α-3H]testosterone and [7α-3H]androstenedione. The metabolites identified were androstenedione, 5α-androstane-3,17-dione, androsterone, 3-epiandrosterone, 5α-dihydrotestosterone, 5α-androstane-3α,17β-diol, 5α-androstane-3β,17β-diol, 5-androstene-3β,17β-diol and testosterone. The results provide evidence for the presence of 3β-hydroxysteroid dehydrogenase, Δ4–5 isomerase, 17β-hydroxysteroid dehydrogenase, Δ4-3-oxosteroid-5α-reductase and 3α-hydroxysteroid dehydrogenase in human foetal skin. There were quantitative differences in the various enzyme activities between different body sites and skin specimens of different gestational age. 5α-Reductase activity was particularly high in genital skin. 3β-Hydroxysteroid dehydrogenase Δ4–5 isomerase activity was low in skin from a 12-week foetus, but high in skin specimens from 28-, 38- and 41-week foetuses. 17β-Hydroxysteroid dehydrogenase activity was already high in the skin of the 12-week foetus and remained so in the older foetuses. These results were correlated with the development of the foetal sebaceous glands, and were in general agreement with a parallel enzyme histochemical study. The role of androgen metabolism in human foetal skin is discussed.

IN VITRO EFFECT OF 16α-HYDROXYPROGESTERONE ON THE ENZYME ACTIVITIES RELATED TO ANDROGEN PRODUCTION IN HUMAN TESTES

1978 ◽  
Vol 88 (4) ◽  
pp. 768-777 ◽  
Author(s):  
Hiroshi Inano ◽  
Bun-ichi Tamaoki
Keyword(s):  
Enzyme Activities ◽  
Incubation Medium ◽  
Prostatic Carcinoma ◽  
Microsomal Fraction ◽  
Hydroxysteroid Dehydrogenase ◽  
Steroid Metabolism ◽  
Side Chain ◽  
Cytosol Fraction ◽  
Vitro Effect

ABSTRACT Progesterone was converted in vitro to 16α- and 17α-hydroxyprogesterones in the presence of NADPH by the testicular microsomal fraction (precipitate at 10 000 × g−105 000 × g) obtained from patients with prostatic carcinoma. 16α-Hydroxyprogesterone was not metabolized by either the microsomal or the cytosol fractions, and accumulated in the incubation medium. 16α-Hydroxyprogesterone competitively inhibited the activity of the C-17−C-20 lyase in the testicular microsomal fraction with an estimated inhibitor constant of 72 μm. Moreover, the 16α-hydroxyprogesterone non-competitively inhibited the activity of the 20α-hydroxysteroid dehydrogenase in the testicular cytosol fraction and had an estimated inhibitor constant of 52.9 μm. Other testicular enzymes related to steroid metabolism, such as Δ5-3β-hydroxysteroid dehydrogenase coupled with the Δ4-Δ5 isomerase, 16α-hydroxylase, 17α-hydroxylase and 17β-hydroxysteroid dehydrogenase were not influenced in vitro by 16α-hydroxyprogesterone at the concentration of 0.1 mm. From these findings, it is concluded that 16α-hydroxyprogesterone inhibit specifically the cleavage of the side-chain of 17α-hydroxypregnenes in the course of androgen formation from pregnenolone in vitro.

Desmosomal distribution in the epidermis of a non-contracting human skin equivalent

1992 ◽  
Vol 50 (1) ◽  
pp. 896-897
Author(s):  
L.X. Oakford ◽  
S.D. Dimitrijevich ◽  
R. Gracy
Keyword(s):  
Human Skin ◽  
Basal Layer ◽  
Skin Equivalent ◽  
Tissue Component ◽  
Intact Skin ◽  
Similar Sequence ◽  
Sequence Of Events ◽  
Suprabasal Keratinocytes ◽  
Human Skin Equivalent

In intact skin the epidermal layer is a dynamic tissue component which is maintained by a basal layer of mitotically active cells. The protective upper epidermis, the stratum corneum, is generated by differentiation of the suprabasal keratinocytes which eventually desquamate as anuclear comeocytes. A similar sequence of events is observed in vitro in the non-contracting human skin equivalent (HSE) which was developed in this lab (1). As a part of the definition process for this model of living skin we are examining its ultrastructural features. Since desmosomes are important in maintaining cell-cell interactions in stratified epithelia their distribution in HSE was examined.

REGULATION OF THE ACTIVITIES OF THE ENZYMES INVOLVED IN THE METABOLISM OF STEROID HORMONES IN RAT LIVER: THE EFFECT OF 19-NORTESTOSTERONE AND THE INFLUENCE OF CYPROTERONE ACETATE ON THE ACTION OF TESTOSTERONE AND 5α-DIHYDROTESTOSTERONE

1974 ◽  
Vol 77 (2) ◽  
pp. 287-297 ◽  
Author(s):  
Rüdiger Ghraf ◽  
Edmund Rodney Lax ◽  
Hanns-Georg Hoff ◽  
Herbert Schriefers
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Rat Liver ◽  
Enzyme Activities ◽  
Cyproterone Acetate ◽  
Hydroxysteroid Dehydrogenase ◽  
Seminal Vesicles ◽  
Normal Male ◽  
Steroid Hydroxylases ◽  
Drug Leads

ABSTRACT The androgens testosterone and 5α-dihydrotestosterone, the anabolic drug 19-nortestosterone and the anti-androgen cyproterone acetate were investigated with regard to their modifying action on the sexual differentiation of the activities of rat liver enzymes involved in steroid hormone metabolism. The activities of the enzymes (Δ4-5α-hydrogenase, 20-ketoreductase, 3α-and 3β-hydroxysteroid dehydrogenase, NAD- and NADP-dependent Δ4-3β-hydroxysteroid dehydrogenase, total steroid hydroxylases, 7α- and 16α-hydroxylase) were determined in cell-free liver fractions of male animals castrated on day 25 of life and killed on day 90; and of castrated animals which, from day 75 to 89 received daily sc injections (0.3 mg/100 g body weight) of the anabolic drug or the androgen only or in combination with cyproterone acetate (3 mg/100 g body weight). With the exception of 7α-hydroxylase castration leads to a feminization of the enzyme activity pattern. However, the degree of feminization varies from enzyme to enzyme. The administration of testosterone or of 5α-dihydrotestosterone reverses the effect of castration. With 5α-dihydrotestosterone activity values were reached which in some cases were significantly higher than those obtained with testosterone. Although both androgens restored the enzyme activities to the normal male values, neither androgen was able to compensate for the weight loss of the seminal vesicles in the dose administered. The administration of 19-nortestosterone in the same dose as testosterone is only 30 % as effective in restoring the weight loss of the seminal vesicles, but leads to identical activities of Δ4-5α-hydrogenase and of hydroxysteroid dehydrogenases as are found for testosterone. 19-Nortestosterone is without influence on the activities of total steroid hydroxylases and of 16α-hydroxylase. 16α-Hydroxylase is the only enzyme in which the activity enhancing effects of testosterone or of 5α-dihydrotestosterone can be completely blocked by the simultaneous administration of the anti-androgen cyproterone acetate. In all other enzyme activities the anti-androgen does not interfere with the effect of the androgens although it blocks their action on the weight restitution of the seminal vesicles by 60–70 %. 7α-Hydroxylase does not exhibit any androgen dependency. Neither castration nor the subsequent administration of the two androgens, or of the anabolic drug leads to any alterations in activity. However, it is interesting to note that the administration of cyproterone acetate does cause an increase in activity.

Oxygenation of 18-hydroxycorticosterone as the final reaction for aldosterone biosynthesis

1984 ◽  
Vol 107 (3) ◽  
pp. 395-400 ◽  
Author(s):  
Itaru Kojima ◽  
Etsuro Ogata ◽  
Hiroshi Inano ◽  
Bun-ichi Tamaoki
Keyword(s):  
Carbon Monoxide ◽  
Hydroxysteroid Dehydrogenase ◽  
Dependent Manner ◽  
In Vitro Production ◽  
Mitochondrial Preparation ◽  
Final Reaction ◽  
Vitro Production ◽  
Dose Dependent ◽  
Cytochrome P 450

Abstract. Incubation of 18-hydroxycorticosterone with the sonicated mitochondrial preparation of bovine adrenal glomerulosa tissue leads to the production of aldosterone, as measured by radioimmunoassay. The in vitro production of aldosterone from 18-hydroxycorticosterone requires both molecular oxygen and NADPH, and is inhibited by carbon monoxide. Cytochrome P-450 inhibitors such as metyrapone, SU 8000. SU 10603, SKF 525A, amphenone B and spironolactone decrease the biosynthesis of aldosterone from 18-hydroxycorticosterone. These results support the conclusion that the final reaction in aldosterone synthesis from 18-hydroxycorticosterone is catalyzed by an oxygenase, but not by 18-hydroxysteroid dehydrogenase. By the same preparation, the production of [3H]aldosterone but not [3H]18-hydroxycorticosterone from [1,2-3H ]corticosterone is decreased in a dose-dependent manner by addition of non-radioactive 18-hydroxycorticosterone.

Human Skin-Derived Fibroblasts Acquire In Vitro Anti-Tumor Potential after Priming with Paclitaxel

2013 ◽  
Vol 13 (3) ◽  
pp. 523-530 ◽  
Author(s):  
Augusto Pessina ◽  
Valentina Cocce ◽  
Arianna Bonomi ◽  
Loredana Cavicchini ◽  
Francesca Sisto ◽  
...  
Keyword(s):  
Human Skin
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