The 3β-Hydroxysteroid Dehydrogenase/Isomerase Gene Family: Lessons from Type II 3β-HSD Congenital Deficiency

Labrie, Fernand; Simard, Jacques; Luu‐The, Van; Bélanger, Alain; Pelletier, Georges; Morel, Yves; Mébarki, Farida; Sánchez, Rocío; Durocher, Francine; Turgeon, Carl; Labrie, Yvan; Rhéaume, Éric; Labrie, Claude; Lachance, Yves

doi:10.1007/978-3-662-03230-5_10

Cited by 27 publications

(20 citation statements)

References 110 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While the present data demonstrate a completely different pattern of effect of EM-800 and tamoxifen on 17␤-HSD activity, the assay using tissue homogenate does not permit conclusions to be drawn about the situation in intact cells. In fact, the predominance of NAD ϩ and NADPH in the intact cells regulates individual isoenzymes having exclusive reductive or oxydative activities (Labrie et al, 1996;Luu-The et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Comparative effects of 28-day treatment with the new anti-estrogen EM-800 and tamoxifen on estrogen-sensitive parameters in intact mice

et al. 1997

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Comparative effects of 28-day treatment with the new anti-estrogen EM-800 and tamoxifen on estrogen-sensitive parameters in intact mice

et al. 1997

View full text Add to dashboard Cite

“…Since the molecular structure of the key non-P450-dependent enzymes involved in sex steroid formation had not been elucidated and knowing that local formation of sex steroids plays a major role in both normal and tumoral hormone-sensitive tissues (Labrie et al 1985a), an important proportion of the research program of many groups, including ours, has been devoted to this exciting and therapeutically promising area (for reviews see Labrie et al 1992bLabrie et al , 1993Labrie et al , 1996b. It is important to mention that 40% of all cancers, namely breast, prostate, ovarian and uterine cancers, are sex steroid-sensitive and are thus prime candidates for approaches based upon control of intracrine activity.…”

Section: The 17 -Hydroxysteroid Dehydrogenases Key Enzymes Acting Atmentioning

confidence: 99%

Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease

Labrie¹,

Luu‐The²,

Lin³

et al. 2000

Journal of Molecular Endocrinology

259

166

View full text Add to dashboard Cite

In women and men, an important proportion of estrogens and androgens are synthesized locally at their site of action in peripheral target tissues. This new field of endocrinology has been called intracrinology. In postmenopausal women, 100% of active sex steroids are synthesized in peripheral target tissues from inactive steroid precursors while, in adult men, approximately 50% of androgens are made locally in intracrine target tissues. The last and key step in the formation of all estrogens and androgens is catalyzed by members of the family of 17 -hydroxysteroid dehydrogenases (17 -HSDs) while different 17 -HSDs inactivate these steroids in the same cell where synthesis takes place. To date, seven human 17 -HSDs have been cloned, sequenced and characterized. The 17 -HSDs provide each cell with the means of precisely controlling the intracellular concentration of each sex steroid according to local needs.

show abstract

“…Humans, along with the other primates, are unique among animal species in having adrenals that secrete large amounts of the inactive precursor steroids dehydroepiandrosterone (DHEA) and especially DHEA-sulfate (DHEA-S), which are converted into potent androgens and/or estrogens in peripheral tissues (Labrie 1991, Labrie et al 1995a, 1996b, 1997d, 2000b, Luu-The 2001 (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Is dehydroepiandrosterone a hormone?

Labrie¹,

Luu‐The²,

Bélanger³

et al. 2005

Journal of Endocrinology

387

242

View full text Add to dashboard Cite

Dehydroepiandrosterone (DHEA) is not a hormone but it is a very important prohormone secreted in large amounts by the adrenals in humans and other primates, but not in lower species. It is secreted in larger quantities than cortisol and is present in the blood at concentrations only second to cholesterol. All the enzymes required to transform DHEA into androgens and/or estrogens are expressed in a cellspecific manner in a large series of peripheral target tissues, thus permitting all androgen-sensitive and estrogensensitive tissues to make locally and control the intracellular levels of sex steroids according to local needs. This new field of endocrinology has been called intracrinology. In women, after menopause, all estrogens and almost all androgens are made locally in peripheral tissues from DHEA which indirectly exerts effects, among others, on bone formation, adiposity, muscle, insulin and glucose metabolism, skin, libido and well-being. In men, where the secretion of androgens by the testicles continues for life, the contribution of DHEA to androgens has been best evaluated in the prostate where about 50% of androgens are made locally from DHEA. Such knowledge has led to the development of combined androgen blockade (CAB), a treatment which adds a pure anti-androgen to medical (GnRH agonist) or surgical castration in order to block the access of the androgens made locally to the androgen receptor. In fact, CAB has been the first treatment demonstrated to prolong life in advanced prostate cancer while recent data indicate that it can permit long-term control and probably cure in at least 90% of cases of localized prostate cancer. The new field of intracrinology or local formation of sex steroids from DHEA in target tissues has permitted major advances in the treatment of the two most frequent cancers, namely breast and prostate cancer, while its potential use as a physiological HRT could well provide a physiological balance of androgens and estrogens, thus offering exciting possibilities for women's health at menopause.

show abstract

The 3β-Hydroxysteroid Dehydrogenase/Isomerase Gene Family: Lessons from Type II 3β-HSD Congenital Deficiency

Cited by 27 publications

References 110 publications

Comparative effects of 28-day treatment with the new anti-estrogen EM-800 and tamoxifen on estrogen-sensitive parameters in intact mice

Comparative effects of 28-day treatment with the new anti-estrogen EM-800 and tamoxifen on estrogen-sensitive parameters in intact mice

Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease

Is dehydroepiandrosterone a hormone?

Contact Info

Product

Resources

About