Transgenic Male Mice Expressing Human Hydroxysteroid Dehydrogenase 2 Indicate a Role for the Enzyme Independent of Its Action on Sex Steroids

ABSTRACT The 17β-hydroxysteroid dehydrogenase activity in intact erythrocytes of Nigerian patients, in particular with regard to haemoglobin genotypes and G6PD* activity was studied. The G6PD activity of the erythrocyte did not affect the oxidative transformation of testosterone to androstenedione and of oestradiol to oestrone. The reduction (reverse transformation) was inhibited in G6PD-deficient erythrocytes but this inhibition was offset by the addition of 0.025 m glucose to the incubation medium. The per cent oxidation transformation of testosterone was higher in Hb-AA than in Hb-SS erythrocytes. It is suggested that the differences may be a result of either lower enzyme activity in the Hb-SS erythrocytes or of differences in the uptake and possibly binding of sex steroids by intact Hb-SS and Hb-AA erythrocytes.

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Sex steroids and leptin regulate 11β-hydroxysteroid dehydrogenase I and P450 aromatase expressions in human preadipocytes: Sex specificities

The Journal of Steroid Biochemistry and Molecular Biology ◽

10.1016/j.jsbmb.2006.01.007 ◽

2006 ◽

Vol 99 (4-5) ◽

pp. 189-196 ◽

Cited By ~ 53

Author(s):

Marie-Noëlle Dieudonné ◽

Anes Sammari ◽

Esther Dos Santos ◽

Marie-Christine Leneveu ◽

Yves Giudicelli ◽

...

Keyword(s):

Sex Steroids ◽

Hydroxysteroid Dehydrogenase ◽

P450 Aromatase ◽

Human Preadipocytes

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11 Structure, regulation and role of 3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase and aromatase enzymes in the formation of sex steroids in classical and peripheral intracrine tissues

Baillière s Clinical Endocrinology and Metabolism ◽

10.1016/s0950-351x(05)80261-7 ◽

1994 ◽

Vol 8 (2) ◽

pp. 451-474 ◽

Cited By ~ 51

Author(s):

Fernand Labrie ◽

Jacques Simard ◽

Van Luu-The ◽

Georges Pelletier ◽

Khalid Belghmi ◽

...

Keyword(s):

Sex Steroids ◽

Hydroxysteroid Dehydrogenase ◽

Structure Regulation

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Selective Vulnerability of Striatal D2 versus D1 Dopamine Receptor-Expressing Medium Spiny Neurons in HIV-1 Tat Transgenic Male Mice

Journal of Neuroscience ◽

10.1523/jneurosci.0622-17.2017 ◽

2017 ◽

Vol 37 (23) ◽

pp. 5758-5769 ◽

Cited By ~ 20

Author(s):

Christina J. Schier ◽

William D. Marks ◽

Jason J. Paris ◽

Aaron J. Barbour ◽

Virginia D. McLane ◽

...

Keyword(s):

Dopamine Receptor ◽

Selective Vulnerability ◽

Medium Spiny Neurons ◽

Male Mice ◽

Spiny Neurons ◽

D1 Dopamine Receptor ◽

Hiv 1 ◽

Transgenic Male

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ONTOGENETIC AND PHYLOGENETIC DISTRIBUTION OF HYDROXYSTEROID DEHYDROGENASES IN THE VERTEBRATE KIDNEY

Journal of Endocrinology ◽

10.1677/joe.0.0360029 ◽

1966 ◽

Vol 36 (1) ◽

pp. 29-NP ◽

Cited By ~ 7

Author(s):

A. H. BAILLIE ◽

M. M. FERGUSON ◽

D. McK. HART

Keyword(s):

Dehydrogenase Activity ◽

Sex Steroids ◽

Hydroxysteroid Dehydrogenase ◽

Phylogenetic Distribution ◽

Hydroxysteroid Dehydrogenases ◽

Collecting Tubules ◽

Convoluted Tubules

SUMMARY The human pronephros showed no hydroxysteroid dehydrogenase activity. The human mesonephros, like piscine and amphibian mesonephroi had 16β- and 17β-hydroxysteroid dehydrogenase activity and a possible function of the human mesonephros is suggested. Metanephric kidneys had 3α-, Δ5-3β-, 3β-, 6β-, 16α-, 16β-, and 17β-hydroxysteroid dehydrogenases; 11β-hydroxysteroid dehydrogenase was present in all adult mammalian metanephric kidneys surveyed. 3α-Hydroxysteroid dehydrogenase was selectively present and very active in the proximal and distal convoluted tubules, particularly of the juxta-medullary glomeruli. This function is thought to be related to the excretion of 3α-ketosteroids. 11β-Hydroxysteroid dehydrogenase was confined to the collecting tubules and its possible involvement in the metabolism of cortisol, aldosterone or androgens in the kidney is noted. 17β-Hydroxysteroid dehydrogenase may be concerned in the excretion of the sex steroids; it occurs throughout the nephron. Δ5-3β-, 16α-, and 16β-hydroxysteroid dehydrogenases were not as active histochemically in the kidney as the 3α-, 3β-, 11β- and 17β-hydroxysteroid dehydrogenases.

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Altered Structure and Function of Reproductive Organs in Transgenic Male Mice Overexpressing Human Aromatase*

Endocrinology ◽

10.1210/endo.142.6.8211 ◽

2001 ◽

Vol 142 (6) ◽

pp. 2435-2442 ◽

Cited By ~ 78

Author(s):

Xiangdong Li ◽

Elina Nokkala ◽

Wei Yan ◽

Tomi Streng ◽

Niina Saarinen ◽

...

Keyword(s):

Reproductive Organs ◽

Structure And Function ◽

Male Mice ◽

Human Aromatase ◽

And Function ◽

Transgenic Male

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Osteoprotegerin-Deficient Male Mice as a Model for Severe Alveolar Bone Loss: Comparison With RANKL-Overexpressing Transgenic Male Mice

Endocrinology ◽

10.1210/en.2012-1928 ◽

2013 ◽

Vol 154 (2) ◽

pp. 773-782 ◽

Cited By ~ 33

Author(s):

Masanori Koide ◽

Yasuhiro Kobayashi ◽

Tadashi Ninomiya ◽

Midori Nakamura ◽

Hisataka Yasuda ◽

...

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Alveolar Bone ◽

Nuclear Factor Κb ◽

Alveolar Bone Loss ◽

Male Mice ◽

Periodontal Tissues ◽

Cortical Areas ◽

Immunohistochemical Analyses ◽

Transgenic Male

Periodontitis, an inflammatory disease of periodontal tissues, is characterized by excessive alveolar bone resorption. An increase in the receptor activator of nuclear factor-κB ligand (RANKL) to osteoprotegerin (OPG) ratio is thought to reflect the severity of periodontitis. Here, we examined alveolar bone loss in OPG-deficient (OPG−/−) mice and RANKL-overexpressing transgenic (RANKL-Tg) mice. Alveolar bone loss in OPG−/− mice at 12 weeks was significantly higher than that in RANKL-Tg mice. OPG−/− but not RANKL-Tg mice exhibited severe bone resorption especially in cortical areas of the alveolar bone. An increased number of osteoclasts was observed in the cortical areas in OPG−/− but not in RANKL-Tg mice. Immunohistochemical analyses showed many OPG-positive signals in osteocytes but not osteoblasts. OPG-positive osteocytes in the cortical area of alveolar bones and long bones were abundant in both wild-type and RANKL-Tg mice. This suggests the resorption in cortical bone areas to be prevented by OPG produced locally. To test the usefulness of OPG−/− mice as an animal model for screening drugs to prevent alveolar bone loss, we administered an antimouse RANKL antibody or risedronate, a bisphosphonate, to OPG−/− mice. They suppressed alveolar bone resorption effectively. OPG−/− mice are useful for screening therapeutic agents against alveolar bone loss.

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Testosterone signaling through ZIP9 renders melanoma more aggressive in males than in females

10.1101/2020.03.12.989160 ◽

2020 ◽

Cited By ~ 2

Author(s):

Cristina Aguirre-Portolés ◽

Riley Payne ◽

Aspen Trautz ◽

J. Kevin Foskett ◽

Christopher A. Natale ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Estrogen Receptors ◽

Sex Steroids ◽

Nuclear Translocation ◽

Human Melanoma ◽

Zinc Transporter ◽

Male Mice ◽

Mapk Activation ◽

Worse Prognosis

AbstractMelanoma and most other cancers occur more frequently, and have worse prognosis, in males compared with females. Though sex steroids are thought to be involved, classical androgen and estrogen receptors are not detectable in most melanomas. Here we show that testosterone promotes melanoma proliferation by activating ZIP9 (SLC39A9), a zinc transporter that is not intentionally targeted by available therapeutics, but is widely expressed in human melanoma. This testosterone activity requires zinc influx, MAPK activation and YAP1 nuclear translocation. We demonstrate that FDA approved inhibitors of the classical androgen receptor also inhibit ZIP9, and thereby antagonize the pro-tumorigenic effects of testosterone in melanoma. In male mice, androgen receptor inhibitors suppressed growth of ZIP9-expressing melanomas, but had no effect on isogenic melanomas lacking ZIP9, nor on melanomas in females. These data suggest that ZIP9 might be effectively targeted in melanoma and other cancers by repurposing androgen receptor inhibitors that are currently approved only for prostate cancer.

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Immunoelectron microscopic localization of 3beta-hydroxysteroid dehydrogenase and type 5 17beta-hydroxysteroid dehydrogenase in the human prostate and mammary gland

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0260011 ◽

2001 ◽

Vol 26 (1) ◽

pp. 11-19 ◽

Cited By ~ 30

Author(s):

G Pelletier ◽

V Luu-The ◽

M El-Alfy ◽

S Li ◽

F Labrie

Keyword(s):

Endothelial Cells ◽

Mammary Gland ◽

Epithelial Cells ◽

Blood Vessels ◽

Sex Steroids ◽

Cell Types ◽

Hydroxysteroid Dehydrogenase ◽

Human Prostate ◽

Peripheral Tissues ◽

Gold Particles

The subcellular distribution of steroidogenic enzymes has so far been studied mostly in classical endocrine glands and in the placenta. In the peripheral intracrine organs which synthesize sex steroids there is no indication about the organelles which contain the enzymes involved in steroid biosynthesis. We have thus investigated the subcellular localization of two enzymes involved in the production of sex steroids, namely 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and type 5 17beta-hydroxysteroid dehydrogenase (17beta-HSD). Using specific antibodies to these enzymes, we conducted immunoelectron microscopic studies in two peripheral tissues, namely the human prostate and mammary gland. In the prostate, immunolabelling for both 3beta-HSD and type 5 17beta-HSD was detected in the basal cells of the tube-alveoli as well as in fibroblasts and endothelial cells lining the blood vessels. In all the labelled cell types, the gold particles were distributed throughout the cytoplasm. No obvious association with any specific organelle could be observed, although some concentration of gold particles was occasionally found over bundles of microfilaments. In mammary gland sections immunolabelled for 3beta-HSD or type 5 17beta-HSD localization, labelling was observed in the cytoplasm of the secretory epithelial cells in both the acini and terminal ducts. Immunolabelling was also found in the endothelial cells as well as in fibroblasts in stroma and blood vessels. The gold particles were not detected over any organelles, except with the occasional accumulation of gold particles over microfilaments. The present data on the localization of two steroidogenic enzymes leading to the synthesis of testosterone indicate that these enzymes are located not only in epithelial cells but also in stromal and endothelial cells in both tissues studied. The absence of any association of the enzymes with membrane-bound organelles appears as a common finding in the reactive cell types of two peripheral tissues.

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