Androgene und Androgenmangel bei Tiermodellen der Osteoporose

Zusammenfassung

Hypogonadismus ist einer der wichtigsten Risikofaktoren der Osteoporose des Mannes. Tiermodelle, insbesondere Ratten- und Mäusemodelle, sind dazu verwendet worden, das Wissen über die Skelettwirkungen von Androgenen zu vermehren. Androgenmangel während des Wachstums führt zu einem inad- äquaten Aufbau von insbesondere kortikaler Knochenmasse, während die Orchiektomie von alten, nicht mehr wachsenden Ratten einen ausgeprägten und lang anhaltenden Anstieg des Knochenturnovers induziert, der zum Verlust von trabekulärem und endokortikalem Knochen führt. Die letzteren Veränderungen spiegeln sehr gut die Veränderungen wider, die durch Androgenmangel bei adulten Männern induziert werden. Der Anstieg der Knochenresorption bei alten orchiektomierten Ratten ist verknüpft mit einem Anstieg der Konzentration an freiem löslichem RANKL im Knochenmark. Obwohl klar ist, dass der männliche Knochenstoffwechsel sowohl über den Androgenals auch über den Östrogenrezeptor-α (ER) beeinflusst werden kann, haben eine Reihe von klinischen Daten und Daten aus Tierexperimenten nahe gelegt, dass der Erhaltung der trabekulären und endokortikalen Skelettmasse unter physiologischen Bedingungen hauptsächlich ein ER-vermittelter Signalweg nach Aromatisierung von Androgenen zu Östrogenen zugrunde liegt.

Summary

Hypogonadism is considered to be one of the major risk factors for osteoporosis in men. Animal models, especially rats and mice, have been used to improve our understanding of the skeletal effects of androgens. Androgen deficiency during growth is associated with a failure to acquire normal peak bone mass, whereas orchiectomy of aged, nongrowing male rats is associated with a pronounced and sustained increase in bone turnover and with a concomitant loss of cancellous and endocortical bone, closely mimicking the conditions induced by androgen withdrawal in adult humans. The increase in bone resorption found in aged androgen deficient rats is associated with an upregulation of free soluble RANKL in bone marrow. Although there is firm evidence that male bone metabolism can be influenced via the androgen and the estrogen receptor-α (ER), a variety of clinical and animal experimental data have suggested that, under physiological conditions, the maintenance of cancellous and endocortical bone mass in males primarily involves the ER-α-mediated skeletal action of estrogen derived from the aromatization of androgens.

Schlüsselwörter

Androgene - Östrogene - Tiermodell - Osteoporose

Keywords

Androgens - estrogens - animal model - osteoporosis

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