The Human Rights Campaign (HRC), the nation's largest gay rights advocate, has asked comedian David Letterman to apologize for a joke the group has labeled “transphobic.”

On Tuesday, during Letterman's opening Late Show monologue, the show's announcer, Alan Kalter, feigned “trans panic” when Letterman announced that President Obama's historic appointment to the U.S. Department of Commerce, Amanda Simpson, was a transgender woman.

“What? Amanda used to be a dude? Oh my God!,” Kalter screamed in disgust and then ran off the stage upon hearing the news.

In a letter address to David Letterman and carbon copied to Nina Tassler, president of CBS Entertainment, HRC called the skit “inappropriate.”

“The decision to ignore the fact that Ms. Simpson is incredibly well-qualified for this vital national security position and focus instead on her gender identity reflects transphobia.”

“You may not be aware that the punch line in your skit has been used as a defense in nearly every hate crime perpetrated against transgender people that has come to trial,” HRC said.

The Gay & Lesbian Alliance Against Defamation (GLAAD), a GLBT media watchdog group, also asked for an apology.

“Amanda Simpson and transgender people want the same things all Americans do: to earn a living and be recognized for their contributions to society,” Jarrett Barrios, president of GLAAD, said in a statement. “Instead of using humor to raise awareness about the lives of transgender people, the show ridiculed the first transgender presidential appointee and one of the most vulnerable minorities in this country.”

“By promoting unfair and cruel reactions to transgender people, the David Letterman Show is feeding an epidemic of discrimination and violence that currently faces transgender Americans,” he added.

Simpson, 48, began her job Tuesday as senior technical advisor to the Department of Commerce.