Whether from endogenous or exogenous sources, 17β-estradiol (E2) exerts powerful influences over female reproductive processes. It is generally assumed that steroid hormones act within the body whose glands produce these hormones, but we demonstrated that E2 can also be shared between individuals. Male mice were given doses of tritiated estradiol (3H-E2) representing a small fraction of their endogenous E2, then housed with untreated females. After 48 hours of cohabitation, radioactivity was found in the uterus, ovaries, mesencephalon and diencephalon, and other peripheral and brain tissues of untreated female cohabitants1,2. We then tested species generality of male-to-female E2 transfer using big brown bats, which are phylogenetically very distant from mice. We found substantial radioactivity in the uterus, ovaries, hypothalamus, and other brain and peripheral tissues of untreated female bats after 48 hours with 3H-E2-treated male bats. In both species, 3H-E2 was readily absorbed into females’ circulation nasally and percutaneously, facilitated by low molecular mass and highly lipophilic nature. In mice, 3H-E2 transfers much more than does 3H-progesterone, due to poorer absorption of 3H-progesterone by untreated females. Pre-treating females with unlabelled E2 reduces the presence of radioactivity in the uterus and other tissues after cohabitation with a 3H-E2-treated mouse, suggesting that the transferred 3H-E2 remains bioactive2.
We have extensive data from mice linking transferred E2 to pheromonal phenomena. Male mice actively target nearby females with their urine, which contains substantial quantities of bioactive (unconjugated) E23,4. Very low doses of exogenous E2 mimic the Vandenbergh effect (male-induced promotion of female puberty) and the Bruce effect (novel-male-induced blastocyst implantation failure). There are established mechanisms by which reproductive maturation is promoted by E2 actions at the hypothalamus and reproductive tract, and by which excessive E2 causes blastocyst implantation failure. Transferred E2 could also explain male-induced estrus and ovulation in a number of mammals.