Somatostatin is essential for the sexual dimorphism of gh secretion, corticosteroid-binding globulin production, and corticosterone levels in mice

Jessica M. Adams, Veronica Otero-Corchon, Geoffrey L. Hammond, Johannes D Veldhuis, Nathan Qi, Malcolm J. Low

Research output: Contribution to journalArticle

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Abstract

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 micro arrays. 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.

Original languageEnglish (US)
Pages (from-to)1052-1065
Number of pages14
JournalEndocrinology
Volume156
Issue number3
DOIs
StatePublished - Mar 1 2015

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Transcortin
Corticosterone
Somatostatin
Knockout Mice
Sex Characteristics
Liver
Messenger RNA
Xenobiotics
Transcriptome
Adrenocorticotropic Hormone
Glucocorticoids
Cerebrospinal Fluid
Steroids

ASJC Scopus subject areas

  • Endocrinology

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Somatostatin is essential for the sexual dimorphism of gh secretion, corticosteroid-binding globulin production, and corticosterone levels in mice. / Adams, Jessica M.; Otero-Corchon, Veronica; Hammond, Geoffrey L.; Veldhuis, Johannes D; Qi, Nathan; Low, Malcolm J.

In: Endocrinology, Vol. 156, No. 3, 01.03.2015, p. 1052-1065.

Research output: Contribution to journalArticle

Adams, Jessica M. ; Otero-Corchon, Veronica ; Hammond, Geoffrey L. ; Veldhuis, Johannes D ; Qi, Nathan ; Low, Malcolm J. / Somatostatin is essential for the sexual dimorphism of gh secretion, corticosteroid-binding globulin production, and corticosterone levels in mice. In: Endocrinology. 2015 ; Vol. 156, No. 3. pp. 1052-1065.
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