Bone protection by estrens occurs through non-tissue-selective activation of the androgen receptor.

Windahl, Sara H,1971Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine (författare)

The use of estrogens and androgens to prevent bone loss is limited by their unwanted side effects, especially in reproductive organs and breast. Selective estrogen receptor modulators (SERMs) partially avoid such unwanted effects, but their efficacy on bone is only moderate compared with that of estradiol or androgens. Estrens have been suggested to not only prevent bone loss but also exert anabolic effects on bone while avoiding unwanted effects on reproductive organs. In this study, we compared the effects of a SERM (PSK3471) and 2 estrens (estren-alpha and estren-beta) on bone and reproductive organs to determine whether estrens are safe and act via the estrogen receptors and/or the androgen receptor (AR). Estrens and PSK3471 prevented gonadectomy-induced bone loss in male and female mice, but none showed true anabolic effects. Unlike SERMs, the estrens induced reproductive organ hypertrophy in both male and female mice and enhanced MCF-7 cell proliferation in vitro. Estrens directly activated transcription in several cell lines, albeit at much higher concentrations than estradiol or the SERM, and acted for the most part through the AR. We conclude that the estrens act mostly through the AR and, in mice, do not fulfill the preclinical efficacy or safety criteria required for the treatment or prevention of osteoporosis.

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
Animals
Bone Diseases
Metabolic
prevention & control
Bone and Bones
drug effects
physiology
Breast Neoplasms
Cell Division
drug effects
Cell Line
Tumor
Estrenes
pharmacology
Estrogen Receptor alpha
deficiency
Female
Humans
Mice
Mice
Inbred C57BL
Mice
Knockout
Orchiectomy
Ovariectomy
Receptors
Androgen
physiology
Selective Estrogen Receptor Modulators
pharmacology

Galien, René (författare)
Chiusaroli, Riccardo (författare)
Clément-Lacroix, Philippe (författare)
Morvan, Frederic (författare)
Lepescheux, Liên (författare)
Nique, François (författare)
Horne, William C (författare)
Resche-Rigon, Michèle (författare)
Baron, Roland (författare)
Göteborgs universitetInstitutionen för medicin, avdelningen för invärtesmedicin (creator_code:org_t)

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