Somatostatin Is Essential for the Sexual Dimorphism of GH Secretion, Corticosteroid-Binding Globulin Production, and Corticosterone Levels in Mice

Distinct male and female patterns of pituitary GH secretion produce sexually differentiated hepatic gene expression profiles, thereby influencing steroid and xenobiotic metabolism. We used a fully automated system to obtain serial nocturnal blood samples every 15 minutes from cannulated wild-type (W...

Full description

Saved in:
Bibliographic Details
Published inEndocrinology (Philadelphia) Vol. 156; no. 3; pp. 1052 - 1065
Main Authors Adams, Jessica M, Otero-Corchon, Veronica, Hammond, Geoffrey L, Veldhuis, Johannes D, Qi, Nathan, Low, Malcolm J
Format Journal Article
LanguageEnglish
Published United States Endocrine Society 01.03.2015
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary:Distinct male and female patterns of pituitary GH secretion produce sexually differentiated hepatic gene expression profiles, thereby influencing steroid and xenobiotic metabolism. We used a fully automated system to obtain serial nocturnal blood samples every 15 minutes from cannulated wild-type (WT) and somatostatin knockout (Sst-KO) mice to determine the role of SST, the principal inhibitor of GH release, in the generation of sexually dimorphic GH pulsatility. WT males had lower mean and median GH values, less random GH secretory bursts, and longer trough periods between GH pulses than WT females. Each of these parameters was feminized in male Sst-KO mice, whereas female Sst-KO mice had higher GH levels than all other groups, but GH pulsatility was unaffected. We next performed hepatic mRNA profiling with high-density microarrays. Male Sst-KO mice exhibited a globally feminized pattern of GH-dependent mRNA levels, but female Sst-KO mice were largely unaffected. Among the differentially expressed female-predominant genes was Serpina6, which encodes corticosteroid-binding globulin (CBG). Increased CBG was associated with elevated diurnal peak plasma corticosterone in unstressed WT females and both sexes of Sst-KO mice compared with WT males. Sst-KO mice also had exaggerated ACTH and corticosterone responses to acute restraint stress. However, consistent with their lack of phenotypic signs of excess glucocorticoids, cerebrospinal fluid concentrations of free corticosterone in Sst-KO mice were not elevated. In summary, SST is necessary for the prolonged interpulse troughs that define masculinized pituitary GH secretion. SST also contributes to sexual dimorphism of the hypothalamic-pituitary-adrenal axis via GH-dependent regulation of hepatic CBG production.
Bibliography:This work was supported by the National Institutes of Health (NIH) Early Stage Training in the Neurosciences Training Grant T32-NS076401 (to J.M.A.). G.L.H. was supported by a Canada Research Chair in Reproductive Health and an operating grant from Canadian Institutes of Health Research (MOP-111102). M.J.L. was supported by a NIH Grant R01-DK066604. This work used core services provided by the University of Michigan Animal Phenotyping Core supported by the Michigan Nutrition and Obesity Research Center and the Michigan Diabetes Research Center (NIH Grants P30-DK089503 and P30-DK020572) and the Molecular Biology Core supported by the Michigan Gastrointestinal Peptide Research Center (NIH Grant P30-DK034933).
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Deceased, 18 February, 2013.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2014-1429