April 26, 2010

Follicle-stimulating Hormone May Affect Bone Loss In Menopausal Women

Diminished bone density is common among menopausal women and raises their risk of osteoporosis, bone fractures and subsequent complications. Research has traditionally focused on therapies that seek to maintain the level of estrogen in the body. This hormone seems to sustain bone health, but it drops to an extremely low level during and after menopause.

However, research conducted by a team at the Medical College of Georgia in Augusta, GA suggests that another hormone, follicle-stimulating hormone (FSH) may also be involved in decreasing bone mineral density during menopause. Dr. Joseph Cannon, Kellett Chair in Allied Health Sciences, presented his team's research at the American Physiological Society's Experimental Biology 2010 conference in Anaheim on April 24-28, 2010.

Increasing FSH Correlates to Decreasing Bone Density

The level of FSH gradually increases in the five years leading up to menopause, when it reaches its peak and estradiol bottoms out. Research has indicated that bone density begins to decrease over the same period of time. Also, data from animal studies indicated a link between FSH and bone density. This led Cannon and his colleagues to probe whether the increase of FSH has an effect on bone density in humans.

Bone mineral density is a balancing act between bone loss and bone growth involving two types of cells in the body: osteoclasts that break down bone, and osteoblasts that regenerate it. During menopausal bone loss, the osteoclasts' destructive activity outweighs the osteoblasts' rebuilding activity, resulting in an overall weakening of the bone.

Cytokines, which are secreted by white blood cells such as monocytes, are thought to play a role in this imbalance. One cytokine in particular, interleukin-1 beta (IL-1), is known to activate osteoclasts. "Our hypothesis was that [FSH] was decreasing bone mineral density by influencing the production or action of cytokines," said Dr. Cannon.

Data in Cells Confirms Hormone's Effect in Women

To test their hypothesis, the researchers conducted a study of 36 women from 20 to 50 years old. By measuring each woman's level of FSH and then using a low-energy x-ray to analyze her bone density, the researchers saw that higher levels of FSH among the women were indeed associated with lower bone density.

These results prompted Cannon and his team to determine the effects of FSH on a cellular level. They collected blood samples from the study participants and isolated the monocytes to investigate the effect of FSH on cells outside of the body.

They discovered that the monocytes that make IL-1 have receptors for FSH. Receptors act like a lock for a key: when the key (FSH) enters the lock (receptor), the cell performs the activity coded by that key. In this case, the researchers determined that FSH stimulates the production of IL-1 if the monocytes have a sufficient number of FSH receptors.

Through further analysis, the researchers were able to confirm that blood FSH levels corresponded to blood levels of IL-1. This suggests that both inside and outside the body, FSH stimulation of monocytes results in the production of IL-1.

The team also compared the amount of IL-1 in the participants' blood to their bone density and saw that the higher the level of IL-1, the lower the bone density, when other factors that control IL-1 activity were taken into account.

"Our current data suggest that if there was a way to modulate FSH receptors on cells, or some other way to modulate the ability of FSH to influence cells, the result might be a new way of treating or preventing osteoporosis," said Dr. Cannon. "These data support the possibility that controlling the actions of FSH may be a therapeutic way of dealing with osteoporosis that will work beyond the scope of treatments that have been used in the past."


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