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Somatostatin is required for masculinization of growth hormone-regulated hepatic gene expression but not of somatic growth.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2001 Jun; Vol. 107 (12), pp. 1571-80. - Publication Year :
- 2001
-
Abstract
- Pulsatile growth hormone (GH) secretion differs between males and females and regulates the sex-specific expression of cytochrome P450s in liver. Sex steroids influence the secretory dynamics of GH, but the neuroendocrine mechanisms have not been conclusively established. Because periventricular hypothalamic somatostatin (SST) expression is greater in males than in females, we generated knockout (Smst(-/-)) mice to investigate whether SST peptides are necessary for sexually differentiated GH secretion and action. Despite marked increases in nadir and median plasma GH levels in both sexes of Smst(-/-) compared with Smst(+/+) mice, the mutant mice had growth curves identical to their sibling controls and retained a normal sexual dimorphism in weight and length. In contrast, the liver of male Smst(-/-) mice was feminized, resulting in an identical profile of GH-regulated hepatic mRNAs between male and female mutants. Male Smst(-/-) mice show higher expression of two SST receptors in the hypothalamus and pituitary than do females. These data indicate that SST is required to masculinize the ultradian GH rhythm by suppressing interpulse GH levels. In the absence of SST, male and female mice exhibit similarly altered plasma GH profiles that eliminate sexually dimorphic liver function but do not affect dimorphic growth.
- Subjects :
- Animals
Body Weight
Female
Genotype
Growth Hormone metabolism
Hypothalamus metabolism
Male
Mice
Mice, Knockout
Pituitary Gland metabolism
RNA, Messenger biosynthesis
Receptors, Somatostatin biosynthesis
Receptors, Somatostatin genetics
Recombination, Genetic
Somatostatin genetics
Transcription, Genetic
Growth Hormone physiology
Liver metabolism
Sex Characteristics
Somatostatin physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9738
- Volume :
- 107
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 11413165
- Full Text :
- https://doi.org/10.1172/JCI11941