The information encoded by the sex steroid hormones testosterone and estrogen: A hypothesis

It is suggested that the sex steroid hormones testosterone and estrogen (SSH) provide receptor cells with reliable information on protein synthesis and on the level of oxidative metabolism in the cells of the gonads. The SSH are derived from the oxidation of cholesterol. This oxidation is a side reaction of the oxidative processes in the mitochondria that generate most of the energy to the organism. The amount of SSH that is synthesized is correlated to the partial pressure of oxygen at the synthesizing cells. The amount of free SSH that a cell can hold is checked by the damage that free steroids may cause. This damage is prevented by proteins that bind with SSH. As a result, SSH levels are correlated also with the ability of the SSH synthesizing cell to produce proteins that bind with them. A cell can only synthesize SSH in relation to the oxidative processes within it and to its ability to produce the binding proteins necessary to prevent the damage caused by SSH. As a result, the information conveyed by SSH is reliable. We examine the specific damage caused by testosterone and estrogen, and suggest why each of them is best suited for its function. Although both SSH can provide similar information on the metabolism in the cells that synthesize them, there are secondary reasons why testosterone and estrogen were selected to serve particular functions. Testosterone improves the efficiency of the proton pump at the mitochondria in producing ATP, but increases oxidative damage. Estrogen on the other hand decreases oxygen damage but also decreases the efficiency of the proton pump. These differences between the two SSH may explain why females use estrogen to inform the body about the activity of the cells in their gonads while males do it by testosterone. The increased oxidative damage may also explain why in males the testosterone that reaches the brain is turned into estrogen. We also suggest why fish use 11-keto testosterone and why insects do not use these two steroids.

► Free sex steroids damage (handicap) DNA and gap junctions unless bound by proteins.
► Handicaps imposed by sex steroids test information on gonad metabolism.
► Testosterone raises the efficiency of ATP synthesis but increases oxidative damage.
► Estrogen can reduce oxidative damage but does not improve ATP synthesis.
► Ketotestosterone used by fish provide sensitive information on oxygen supply.