Hormone therapy without the complications

Using synthetic molecules that mimic the sex hormones, it may be possible to promote the survival of osteoblasts without the complications associated with hormone replacement therapy.

By | March 9, 2001

One of the consequences of the decline in the levels of the female and male sex hormones with age is osteoporosis. Oestrogen replacement therapy can slow or prevent osteoporosis but can also have undesirable effects, for example, an increased risk of endometrial cancer.

In 9 March Cell, Stavros Manolagas and colleagues of the University of Arkansas for Medical Sciences report on the mechanism by which sex hormones protect osteoblasts from undergoing apoptosis.

Using a variety of osteoblast cell lines, they established that both oestrogens and androgens could block the effects of etoposide, dexamethasone or tumour necrosis factor-α, treatments that normally induce apoptosis (Cell 2001, 104:719-730). Furthermore, both oestrogen receptor-α and -β and the androgen receptor transmitted the anti-apoptotic signal with the same efficiency whether the ligand was an oestrogen or androgen. This finding helps explain why either class of sex hormone has been found to be equally effective in treating osteoporosis in both males and females.

Manolagas et al also found that the anti-apoptotic signal leads to phosphorylation of ERK (extracellular signal-regulated kinase), and is distinct from the normal transcriptional activities of the oestrogen and androgen receptors. Peptides that blocked transcriptional activity did not affect the anti-apoptotic signal. An estren, a synthetic ligand that mimics oestrogen, had a potent anti-apoptotic effect but did not elicit transcriptional activity.

It may therefore be possible to design treatments that activate only the anti-apoptosis pathway of oestrogen or androgen receptors in osteoblasts. By not triggering the other effects of sex hormones, the complications of hormone replacement therapy could be avoided.

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