Why do men, and many other male mammals, have nipples, even though they lack the milk-producing equipment that goes with them? This question intrigued Charles Darwin?s grandfather Erasmus Darwin, and many others before and since. Erasmus speculated that male nipples were a relic of a time when mammals were hermaphrodite - male and female in one individual.

And in a way he had touched, at least partly, on the truth. For male and female mammalian embryos start out along a common developmental pathway which, for a short while, has the potential to produce either male or female anatomy.

As development proceeds, sex-specific hormones kick in and channel the embryo along either the male or female route. And the male nipple, so the general consensus goes, is simply a basic piece of mammalian anatomy that happens not to have been written out of the male developmental program.

Developmental biologist Maureen Dunbar from Yale University School of Medicine and her colleagues have been finding out what causes mammary glands to develop so differently in male and female embryos.

In mouse embryos, five rudimentary buds of mammary tissue are formed in both male and female embryos very early in gestation, but in male mice this tissue starts to degenerate within a few days. In fact, in male mouse embryos the mammary buds disappear completely, leaving not even a nipple as a relic of their evanescent existence. In some other male mammals, a small part of the bud is left and it is this that forms the nipple in adult males.

In female mouse embryos the mammary buds survive, and mammary development proceeds to form both the nipples and the internal structures that will develop into functional milk-producing tissue in adult female mice.

Dunbar and colleagues have identified a tongue-twistingly-named protein as one of the key players in establishing this sexual dichotomy. As described in the journal Development [August 1999], they have found that this protein, called PTHrP for short, has a dual role in male and female mammary fate.

In male embryos, it is responsible for preventing the further development of the mammary bud. PTHrP produced by the bud itself stimulates the bud cells to make receptors for the ?male? hormones circulating in male embryos. This feedback mechanism causes the mammary cells to stop developing and eventually to degenerate.

In female mouse embryos on the other hand, PTHrP acts slightly later as an essential stimulus for the mammary buds to grow and differentiate. In female embryos without PTHrP, milk ducts and nipples don?t develop, Dunbar?s group conclude, and the mammary buds break down.