Explanation of Preterm and Reduced Growth and Development Copyright 2013, James Michael Howard, Fayetteville, Arkansas, U.S.A. It is my hypothesis that evolution selected dehydroepiandrosterone (DHEA) because it optimizes replication and transcription of DNA. Therefore DHEA levels affect all tissues and life span. It is also my hypothesis that evolution selected increased testosterone during evolution of primates and humans. ("Androgens in Human Evolution," Rivista di Biologia / Biology Forum 2001; 94: 345-362) This occurred because testosterone increases androgen receptor production which increases absorption and use of dehydroepiandrosterone (DHEA). (Mammals evolved because of selection for DHEA: "Hormones in Mammalian Evolution," Rivista di Biologia / Biology Forum 2001; 94: 177-184.) The effect of increased testosterone in primates / humans occurred because of increased maternal testosterone. This increased androgen receptors within fetal brains which increased growth and development, hence, bigger brains. This reached a maximum in humans with the selection by evolution of females of very high testosterone. (Human male and female testosterone is higher than chimpanzee male and females; human and chimpanzee estrogen are approximately equivalent.) The extra use of DHEA by our bigger brains changes the use of our DHEA by our bodies. Bigger brains produced the changes in our bodies that differentiate us from the other primates because of competition between the brain and other tissues for DHEA. Fetal and maternal testosterone, therefore, will affect growth and development of a fetus by affecting androgen receptor deposition within the brain and body. A woman of high testosterone, therefore, will produce more competition between herself and a fetus for DHEA for growth and development. Since preterm neonates exhibit reduced cerebral and body growth, I suggest this is caused by reduced availability of DHEA for the fetus as a result of the mother's androgen receptors. The midbrain of the fetus will develop more rapidly during this exposure to testosterone because of earlier formation of androgen receptors within the midbrain compared to the later development of the cerebrum. Therefore, the fetus will exhibit less growth and development in the cerebrum and the body as a result of reduced overall DHEA. The midbrain will benefit from a relative increase in its competition with the body and the cerebrum. From above, I suggest all tissues compete for DHEA and some tissues actually participate in stimulation of DHEA production, also, more than others. As I have suggested, above, the midbrain in these fetuses produce more androgen receptors than the cerebrum, therefore, the midbrain should participate more in the production of end-term, fetal DHEA production which initiates birth. This early stimulation of DHEA by the midbrain of these fetuses should stimulate birth, that is, maternal DHEA and fetal DHEA combine to stimulate birth as a signal of midbrain development necessary for life separate from the mother. This could explain why gestation is reduced in these neonates. (I recently responded to Sci Transl Med 2013: "Slower postnatal growth is associated with delayed cerebral cortical maturation in preterm newborns," Vinall, et al. This is derived from that response.}