Figure 1.

Cartoon illustrating the Calcigender paradigm as formulated by De Loof [2]. It says that it is a general principle in the Animal Kingdom that the Ca²⁺-homeostasis system displays substantial differences between males and females. Females extrude more Ca²⁺ than males do, a process in which sex steroids play an important role. Not only an 44+XX and 44+XY chromosomal configuration like in humans, but a variety of other sex-determining systems in other animals all yield such sex-related differential Ca²⁺-homeostasis, invariably with females extruding more Ca²⁺ through their reproduction-related activities than males. Because they are lipophilic, steroid sex hormones enter the membrane system of all cell types. They have effects on the Ca²⁺ system of all cells and tissues, the brain inclusive. The differences in green colour are only meant to indicate that there are differences in the complex whole Ca²⁺-homeostasis system, not to represent quantitative differences only. Indeed [Ca²⁺]i is very variable, e.g. due to short-lived Ca²⁺-puffs [3].