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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)