Testosterone makes male kidneys weaker

2023-09-05 17:03:07

Female kidneys are more resistant to disease and injury, but researchers aren’t quite sure why.

Now, a study that is published in «Developmental Cell» seems to provide a solution to ‘feminise’ male kidneys and make them as resistant as those of women.

Directed by USC Stem Cellthe paper describes how sex hormones drive differences in the kidneys of male and female mice, and also how reduced testosterone can “feminize» this organ and improve its recovery capacity.

“By exploring how differences in male and female kidneys arise during development, we can better understand how to address gender-related health disparities for patients with kidney disease,” said study author Andy McMahon, director of the Eli and Edythe Broad Center for Regenerative Medicine and Research at USC.

The researchers identified more than 1,000 genes with varying levels of activity in the kidneys of male and female mice. The differences were most apparent in the section of the kidney’s filtering unit known as the proximal tubule, responsible for reabsorbing most nutrients such as glucose and amino acids back into the bloodstream. Most of these sex discrepancies in gene activity appeared when the mice entered puberty and became more pronounced when they reached sexual maturity..

Since female kidneys tend to be more resistant to disease and injury, the researchers became interested in how gene activity in the kidneys becomes “feminized” or “masculinized,” and testosterone appeared to be primarily responsible.

To feminize the kidneys of male mice, two strategies were tried that worked equally well: castrating the males before puberty and thereby lowering their natural testosterone levels, or removing cellular sensors known as androgen receptors that respond to male sex hormones.

Interestingly, three months of caloric restriction—which is an indirect way of lowering testosterone—produced a similar effect. Consequently, caloric restriction has already been shown to mitigate certain types of kidney injury in mice.

To re-masculinize the castrated males’ kidneys, the researchers only needed to inject testosterone. Similarly, injection of testosterone masculinized the kidneys of females who had their ovaries removed before puberty.

The team performed similar experiments with mouse livers. Although this organ also shows sex-related differences, the hormones and underlying factors that drive these differences are very different from those involved in the kidney. This suggests that these sex differences between organs arose independently during evolution.

To test whether the same genes are involved in gender-related kidney differences in humans, the scientists analyzed a limited number of kidneys and biopsies from male and female donors. When it came to genes that differed in their activity between the sexes, there was modest overlap between human and mouse genes.

Although much remains to be done in the study of sex-related differences in normal human kidneyssays McMahon. “Given the divergent outcomes for male and female patients with kidney disease and injury, this line of research is important to move toward ultimately closing the gap in these sex-related health disparities.”