Beyond the Pill

Searching for the switch that controls animal reproduction

On its most basic level, animal reproduction appears to be very simple. Eggs produced by females are fertilized by sperm produced by males. That's about where simplicity stops. Fully understanding the delicate and often mysterious workings of reproductive systems is a primary goal of many scientists, including Colorado Agricultural Experiment Station researcher Colin Clay, who seeks a better way to control fertility in mammals.

What causes the female to produce the egg? Or the male the sperm? Not to mention the eternal question of what could possibly cause males and females to put aside all the more pressing needs of survival — food, shelter, and avoiding enemies — for the single-minded pursuit of bringing those eggs and sperm together?

Clay, an assistant professor of physiology who works at Colorado State University's animal reproduction and biotechnology laboratory, is seeking clues to the most basic reproductive mystery. Clay is looking for a "switch" or a common factor that turns reproductive fertility in mammals on and off.

Mammal reproductive systems consist of a complicated interacting world of glands, cells, receptors, genes, hormones, and proteins. It begins in a small region inside the brain called the hypothalamus, which produces the hormone GnRH, or gonadotropin releasing hormone. Upon receiving GnRH through the bloodstream, the pituitary, another organ at the base of the brain, releases hormones called gonadotropins. Clay refers to the gonadotropin hormones as the systems' "accelerators" because they stimulate and maintain testicular or ovarian activity.

To keep the system in balance, the gonadotropin hormones also stimulate production of the two primary sex steroid hormones, testosterone in males and estrogen in females. Clay calls these sex steroids the moderators or "brakes." They act in a negative feedback role to inhibit further release of hormones from the hypothalamus and the pituitary. Clay says the sex steroids are such good brakes, in fact, that they are the primary active ingredients found in most oral contraceptives.

Clay wants to go one step better than regulating reproductive activity by using testosterone and estrogen to apply the brakes. These hormones have several well-documented side effects. He seeks to affect testicular or ovarian activity further upstream in the reproductive process by controlling production of the accelerators — the gonadotropin hormones.

"We and others have found that production of the gonadotropin hormones in response from GnRH requires "turning on" about four different genes in receptor cells of the pituitary gland," says Clay. "These genes carry the genetic code that allows receptor cells to make four different proteins that form the building blocks of gonadotropin hormones. What we don't know for certain is what signals the cell to make the proteins."

So Clay is looking for that signal, or "switch" that starts the production of gonadotropin hormones. Thus far, he and his colleagues have uncovered several clues that point to one master switch, another protein called steroidogenic factor-1, or SF-1.

The potential benefits of better, more efficient fertility control are enormous. Animal producers would no longer have to guess when to pair males with fertile females. Further, by controlling the time of year when females become fertile, ranchers could avoid newborns arriving in the dead of winter and could even plan to have the right kind of feed on hand for new mothers who may need more nutrition.