Somatostatin is required for masculinization of growth hormone-regulated hepatic gene expression but not of somatic growth

Pulsatile growth hormone (GH) secretion differs between males and females a nd regulates the sex-specific expression of cytochrome P450s in liver. Sex steroids influence the secretory dynamics of GH, but the neuroendocrine mec hanisms have not been conclusively established. Because periventricular hyp othalamic somatostatin (SST) expression is greater in males than in females , we generated knockout (Smst(-/-)) mice to investigate whether SST peptide s are necessary for sexually differentiated GH secretion and action. Despit e marked increases in nadir and median plasma GH levels in both sexes of Sm st(-/-) compared with Smst(+/+) mice, the mutant mice had growth curves ide ntical to their sibling controls and retained a normal sexual dimorphism in weight and length. In contrast, the liver of male Smst(-/-) mice was femin ized, resulting in an identical profile of GH-regulated hepatic mRNAs betwe en male and female mutants. Male Smst(-/-) mice show higher expression of t wo SST receptors in the hypothalamus and pituitary than do females. These d ata indicate that SST is required to masculinize the ultradian GH rhythm by suppressing interpulse GH levels. In the absence of SST, male and female m ice exhibit similarly altered plasma GH profiles that eliminate sexually di morphic liver function but do not affect dimorphic growth.