Somatostatin in sexually dimorphic gene expression

Male and female mammals are distinguished not just by their primary sexual characteristics, but also by their different postpartum growth rates and by subtle differences in expression of metabolic genes. The best studied examples of such genes encode isoforms of cytochrome P450 that which are expressed in the liver under control of growth hormone (GH). In the rat, the species that has proved most tractable for these studies, it is not the level of GH that dictates whether these genes are expressed in males or females, but rather the timing of GH expression. Providing a continuous level of GH favors the female expression pattern, whereas "pulsatile" expression of GH, with peaks occurring six times per day, leads to the male pattern. Because the hypothalamic peptide somatostatin (SST) helps regulate secretion of GH, Low et al. have studied the effects of SST-deficiency on sexual development in the mouse. The authors show that, as in rats, wild-type male mice have more dramatic fluctuations in GH levels than do females. The absence of SST does not seem to alter the frequency of the fluctuation, but it raises the GH level at the low point in the cycle so the liver in males is presumably exposed to at least a moderate level of the hormone at all times. The SST mutation leads to a feminized pattern of gene expression in the livers of males, but it has no dramatic effect on the expression pattern in livers of females. Surprisingly, the males and females in this mutant strain maintain their sexually dimorphic sizes and growth rates, suggesting that not all genes that are regulated by pulsatile GH release are equally sensitive to the continued presence of the hormone during the interpulse portion of the cycle.