title: Gender-dependent role of endogenous somatostatin in regulating growth hormone-axis function in mice.
abstract: It has been previously reported that male and female somatostatin (SST) knockout mice (Sst-/-) release more GH, compared with Sst+/+ mice, due to enhanced GH-secretory vesicle release. Endogenous SST may also regulate GH secretion by directly inhibiting GHRH-stimulated GH gene expression and/or by modulating hypothalamic GHRH input. To begin to explore these possibilities and to learn more about the gender-dependent role of SST in modulating GH-axis function, hypothalamic, pituitary, and liver components of the GH-axis were compared in male and female Sst+/+ and Sst-/- mice. Pituitary mRNA levels for GH and receptors for GHRH and ghrelin were increased in female Sst-/- mice, compared with Sst+/+ controls, and these changes were reflected by an increase in circulating GH and IGF-I. Elevated levels of IGF-I in female Sst-/- mice were associated with elevated hepatic mRNA levels for IGF-I, as well as for GH and prolactin receptors. Consistent with the role of GH/IGF-I in negative feedback regulation of hypothalamic function, GHRH mRNA levels were reduced in female Sst-/- mice, whereas cortistatin (CST) mRNA levels were unaltered. In contrast to the widespread impact of SST loss on GH-axis function in females, only circulating GH, hypothalamic CST, and hepatic prolactin receptor expression were up-regulated in Sst-/- male mice, compared with Sst+/+ controls. These results confirm and extend the sexually dimorphic role of SST on GH-axis regulation, and suggest that CST, a neuropeptide that acts through SST receptors to inhibit GH secretion, may serve a compensatory role in maintaining GH-axis function in Sst-/- male mice.
authors.affiliation: Jesse Brown Veterans Affairs Medical Center, Research and Development Division, M.P 151, West Side, 820 South Damen Avenue, Chicago, IL 60612, USA.
authors.forename: Raul M
authors.initials: RM
authors.lastname: Luque
authors.forename: Rhonda D
authors.initials: RD
authors.lastname: Kineman
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017353:Gene Deletion; D013006:Growth Hormone / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism; D011863:Radioimmunoassay; D054440:Receptors, Ghrelin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000097:blood / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D013004:Somatostatin / Q000235:genetics / Q000502:physiology*
chemical_list: D054440:Receptors, Ghrelin; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone