Production, purification, and functional analysis of recombinant human and mouse 17β-hydroxysteroid dehydrogenase type 7

Törn, Svea; Nokelainen, Pasi; Kurkela, Riitta; Pulkka, Anitta E.; Márta, Mészáros; Ghosh, Sikha; Coca‐Prados, Miguel; Peltoketo, Hellevi; Isomaa, Veli; Vihko, Pirkko

doi:10.1016/s0006-291x(03)00694-6

Cited by 104 publications

(66 citation statements)

References 17 publications

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“…Furthermore, hHSD17B1-dependent tumour growth was significantly reduced by HSD17B1 inhibitor treatment (Husen et al 2006). In addition to HSD17B1, several other hHSD17Bs are capable of converting E 1 to E 2 , including HSD17B7 (Torn et al 2003) and HSD17B12 (Luu-The et al 2006), but the role of these enzymes in the extra-gonadal E 2 formation still remains unclear. Although hHSD17B1 expression in various peripheral tissues is low, its catalytic efficacy is markedly higher than those measured for HSD17B7 and HSD17B12 (Luu-The et al 2006), suggesting an important role for HSD17B1 in peripheral E 2 formation.…”

Section: Hsd17b1mentioning

confidence: 99%

The diversity of sex steroid action: novel functions of hydroxysteroid (17β) dehydrogenases as revealed by genetically modified mouse models

Saloniemi

Jokela²,

Strauss³

et al. 2011

Journal of Endocrinology

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Disturbed action of sex steroid hormones, i.e. androgens and estrogens, is involved in the pathogenesis of various severe diseases in humans. Interestingly, recent studies have provided data further supporting the hypothesis that the circulating hormone concentrations do not explain all physiological and pathological processes observed in hormone-dependent tissues, while the intratissue sex steroid concentrations are determined by the expression of steroid metabolising enzymes in the neighbouring cells (paracrine action) and/or by target cells themselves (intracrine action). This local sex steroid production is also a valuable treatment option for developing novel therapies against hormonal diseases. Hydroxysteroid (17b) dehydrogenases (HSD17Bs) compose a family of 14 enzymes that catalyse the conversion between the low-active 17-keto steroids and the highly active 17b-hydroxy steroids. The enzymes frequently expressed in sex steroid target tissues are, thus, potential drug targets in order to lower the local sex steroid concentrations. The present review summarises the recent data obtained for the role of HSD17B1, HSD17B2, HSD17B7 and HSD17B12 enzymes in various metabolic pathways and their physiological and pathophysiological roles as revealed by the recently generated genetically modified mouse models. Our data, together with that provided by others, show that, in addition to having a role in sex steroid metabolism, several of these HSD17B enzymes possess key roles in other metabolic processes: for example, HD17B7 is essential for cholesterol biosynthesis and HSD17B12 is involved in elongation of fatty acids. Additional studies in vitro and in vivo are to be carried out in order to fully define the metabolic role of the HSD17B enzymes and to evaluate their value as drug targets.

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Section: Hsd17b1mentioning

confidence: 99%

The diversity of sex steroid action: novel functions of hydroxysteroid (17β) dehydrogenases as revealed by genetically modified mouse models

Saloniemi

Jokela²,

Strauss³

et al. 2011

Journal of Endocrinology

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“…For example, dihydrotestostoerne can be further metabolized to 5α -androstane-3α, 17β-diol (3α-Diol) or 5α-androstane-3β, 17β-diol (3β-Diol) by the actions of a number of p450 enzymes including 3α hydroxysteroid dehydrogenase (3α-HSD) , 3β hydroxysteroid dehydrogenase (3β-HSD), and 17β-hydroxysteroid dehydrogenase (Jin and Penning, 2001;Weihua et al, 2002;Gangloff et al 2003, Torn et al 2003, Steckelbroeck et al, 2004. Of these enzymes, 5 alpha reductase and 3β-HSD are also involved in the pathways for synthesis and metabolism of other steroids (see figure 2).…”

Section: Androgen Metabolismmentioning

confidence: 99%

An alternate pathway for androgen regulation of brain function: Activation of estrogen receptor beta by the metabolite of dihydrotestosterone, 5α-androstane-3β,17β-diol

Handa

Pak

Kudwa

et al. 2008

Hormones and Behavior

183

122

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The complexity of gonadal steroid hormone actions is reflected in their broad and diverse effects on a host of integrated systems including reproductive physiology, sexual behavior, stress responses, immune function, cognition, and neural protection. Understanding the specific contributions of androgens and estrogens in neurons that mediate these important biological processes is central to the study of neuroendocrinology. Of particular interest in recent years has been the biological role of androgen metabolites. The goal of this review is to highlight recent data delineating the specific brain targets for the dihydrotestosterone metabolite, 5α-androstane, 3β, 17β-diol (3β-Diol). Studies using both in vitro and in vivo approaches provide compelling evidence that 3β-Diol is an important modulator of the stress response mediated by the hypothalmo-pituitary-adrenal axis. Further, the actions of 3β-Diol are mediated by estrogen receptors, and not androgen receptors, often through a canonical estrogen response element in the promoter of a given target gene. These novel findings compel us to re-evaluate the interpretation of past studies and the design of future experiments aimed at elucidating the specific effects of androgen receptor signaling pathways.

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“…The balance between ER-␣-and ER-␤-mediated signaling is critical for the induction of pathological processes. E 2 , 17␤-estradiol; 3␤Adiol, 5␣-androstane-3␤,17␤diol; HSD17␤7, 17␤-hydroxysteroid dehydrogenase type 7 48 ; HSD3␤, 3␤-hydroxysteroid dehydrogenase.…”

Section: Er-␤ Protects Againstmentioning

confidence: 99%

Delay of Postnatal Maturation Sensitizes the Mouse Prostate to Testosterone-Induced Pronounced Hyperplasia

Savolainen

Pakarainen

Huhtaniemi

et al. 2007

The American Journal of Pathology

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The role of estrogens in the etiology of prostate cancer is controversial. To demonstrate the specific effects of estrogens and androgens on the development of the prostatic epithelial hyperplasia, we used luteinizing hormone receptor knockout mice (LuRKO), which are resistant to pituitary regulation mediated by luteinizing hormone, lack postnatal androgen production, and have rudimentary accessory sex glands, the growth of which can be induced with exogenous androgen replacement. This model is thus ideal for the investigation of direct hormonal effects on the prostate. Testosterone, but not 5␣-dihydrotestosterone, replacement from 21 days of life for 8 weeks induced pronounced hyperplasia and inflammation in the prostates of LuRKO mice. Interestingly, 5␣-dihydrotestosterone combined with 17␤-estradiol did not induce hyperplasia or inflammation, and treatments with inhibitors of estrogen action, aromatase inhibitor, and ICI 182780 further exacerbated testosterone-induced hyperplastic growth. However, the activation of estrogen receptor (ER)-␤ with a specific agonist, DPN [2,3-bis(4-hydroxyphenol)-propionitrile], prevented the development of prostatic hyperplasia and inflammation in testosterone-treated LuRKO mice. Thus, it seems that in the presence of sufficient androgenic stimulation, it is the balance between ER-␣-and ER-␤-mediated signaling that determines whether estrogens promote hyperplasia or protect the prostate against hyperplastic changes.

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Production, purification, and functional analysis of recombinant human and mouse 17β-hydroxysteroid dehydrogenase type 7

Cited by 104 publications

References 17 publications

The diversity of sex steroid action: novel functions of hydroxysteroid (17β) dehydrogenases as revealed by genetically modified mouse models

The diversity of sex steroid action: novel functions of hydroxysteroid (17β) dehydrogenases as revealed by genetically modified mouse models

An alternate pathway for androgen regulation of brain function: Activation of estrogen receptor beta by the metabolite of dihydrotestosterone, 5α-androstane-3β,17β-diol

Delay of Postnatal Maturation Sensitizes the Mouse Prostate to Testosterone-Induced Pronounced Hyperplasia

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