As far as anyone knows, Christine Jorgenson was the first transgender of note to gain mainstream media attention in the modern world.
There were others before that; Berlin, Germany in the 1920's had a very active gay, drag and transgender nightclub scene. Going back farther, to the Eighteenth Century, there was the Chevalier D'Eon, and going back to ancient times there was the Roman emperor Elagabalus (also called Heliogabalus) and there was also emperor Nero's transgender/eunuch girlfriend/wife, Sporus. In point of fact, Sporus' intrigues may be the reason later Christian writers interpreted the writings of the Apostle Paul to mean that effeminate men are to be denied the Kingdom of Heaven.
As others have stated, Dr. Renee Richards was the second modern day transgender to garner widespread mainstream media attention, some time in the late 1970's. Somewhere in the late 1980's or early 1990's, Joey Silvera and other producers started utilizing transgender actors in adult entertainment, and according to some, transgender videos are the most popular category among "straight" male viewers (who knew?) Either way, adult entertainment's historical contribution, to bringing transgender into the mainstream, for better or worse, cannot be denied.
Okay, history lesson over.