DALLAS Nov. 20, 2003 Researchers at UT Southwestern Medical Center at Dallas have shown that insulin family signaling is important for male sex determination, a discovery that furthers the understanding of testes formation and eventually could lead to treatments for reproductive disorders.
Their findings appear in the current issue of Nature and are available online.
"We are excited by this research for two reasons," said Dr. Luis Parada, senior author of the Nature study and director of the Center for Developmental Biology. "First, the intracellular signaling pathways that mediate male sexual differentiation have remained elusive despite the fact that the controlling gene that unleashes the process was identified almost 15 years ago. Second, our experience with studying receptors and signaling in development provides us with the skills and tools to tackle this problem, which has tremendous implications in newborn disorders."
UT Southwestern researchers now want to determine if the insulin-signaling pathway is active in human gonad formation. It has been found only in mice, but there is a strong likelihood it exists in humans.
"If the insulin-signaling pathway turns out to be important in humans, we'll be able to activate the pathway because we know what proteins to manipulate," said Dr. Sunita Verma-Kurvari, postdoctoral researcher in the Center for Developmental Biology and co-first author of the study. "We someday may even be able to correct reproductive disorders by activating them with therapeutics."
In mice, the male sex-determining process begins in a region of the Y chromosome called Sry, Dr. Verma-Kurvari said. Sry triggers differentiation of the Sertoli cells, which act as organizing centers and direct formation of the testes.
Without Sry, XX or XY gonads failed to develop testes (male reproductive organs producing sperm and male sex hormones), and male to female sex reversal ensued in the mice
Contact: Scott Maier
UT Southwestern Medical Center