Why nothing works under pressure
Why do men produce less sperm when they are under stress? - Because the production of testosterone in the testes depends on how the stress hormones affect the relevant enzymes. This is reported by a working group led by Population Council endocrinologist Matthew Hardy in the December issue of Endocrinology. They demonstrate for the first time that stress affects the Leydig cells locally within the testicles.
It has long been known that male reproduction is severely inhibited by stress; however, we don't yet know where or how this happens in the complex process of spermatogenesis, says Hardy. But his work not only offers insights into male reproduction; it may also contribute to the development of new male contraceptives. He explains: "Ultimately, I'm interested in controlling testosterone production. Testosterone biosynthesis may provide a pathway to regulation of sperm production.
Hardy discovered receptors in adult Leydig cells that mediate the activity of glucocorticoid hormones. In small amounts, glucocorticoid helps cells grow and thrive. However, when it is produced in large quantities during times of stress, it disrupts normal processes in the body. Too much glucocorticoid impairs the Leydig cell's defense mechanism, which is controlled by an enzyme called 11ßHSD-1. The cell produces only enough 11ßHSD-1 to handle normal levels of glucocorticoid. An excess of hormones overloads the 11ßHSD-1, it can no longer neutralize the glucocorticoid, so that testosterone production is suppressed. Without testosterone, however, the responsible cells do not even begin to produce sperm.
11ßHSD-1 has two opposing tasks, which it fulfills depending on the requirements. During development of Leydig cells, the amount of the enzyme increases in parallel with the amount of glucocorticoid receptors. In immature Leydig cells of young mammals, 11ßHSD-1 enhances the action of glucocorticoid; this helps the Leydig cells to divide. According to Hardy's data, glucocorticoid does for immature Leydig cells what it does for other cells in the body. Fully developed Leydig cells retain their glucocorticoid receptors. However, as soon as the hormone enters mature cells, it disrupts testosterone production. Therefore, the function of the enzyme changes. It now inactivates the glucocorticoid, allowing the cells to produce testosterone.
According to Hardy's data, in addition to the two known forms of 11ßHSD, of which only 11ßHSD-1 is active in the testicles, there is a third variant that was previously unknown. We don't know exactly what this enzyme is, although it is very similar to 11ßHSD-1. We can see what it does. And it's this very enzyme that keeps the Leydig cell producing testosterone, he explains. My theory now is that this stronger enzyme appears as the Leydig cells develop. It may be encoded by a gene closely related to the 11ßHSD gene that is expressed in younger Leydig cells," Hardy says. He believes the reason why no scientist has discovered the novel enzyme in 40 years of research on 11ßHSD is that it shares several characteristics of the known 11ßHSD-1.
Hardy has additional evidence that enzyme activity changes in response to stress. He and his colleagues discovered that dominant rats living under stress produce more testosterone and have higher enzyme activity that counteracts increased glucocorticoid levels. This ensures that they remain fertile.
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