PNA Medical Corner: SSTR5 Inhibits ACTH
This month the PNA Medical Corner spotlights an article co-authored by Dr. Shlomo Melmed of Cedars-Sinai Medical Center in Los Angeles, a longtime member of the PNA. The study looks at somatostatin receptor subtype 5 and its effect on hypothalamic pituitary-adrenal axis stress function.
Read the abstract here:
Somatostatin receptor subtype 5 modifies hypothalamic-pituitary-adrenal axis stress function.Somatostatin receptor subtype 5 modifies hypothalamic-pituitary-adrenal axis stress function.
Yamamoto M1, Ben-Shlomo A1, Kameda H1, Fukuoka H1, Deng N2, Ding Y1, Melmed S1.
JCI Insight. 2018 Oct 4;3(19). pii: 122932. doi: 10.1172/jci.insight.122932. [Epub ahead of print]
1Pituitary Center, Department of Medicine, and.
2Biostatistics and Bioinformatics Research Center, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Pituitary corticotroph somatostatin receptor subtype 5 (SSTR5) signals to inhibit adrenocorticotrophin (ACTH) secretion. As ACTH deficiency results in attenuated adrenal cortisol production and an impaired stress response, we sought to clarify the role of SSTR5 in modifying the hypothalamic/pituitary/adrenal (HPA) axis. We generated Tg HP5 mice overexpressing SSTR5 in pituitary corticotrophs that produce the ACTH precursor proopiomelanocortin (POMC). Basal ACTH and corticosterone were similar in HP5 and WT mice, while HP5 mice showed attenuated ACTH and corticosterone responses to corticotrophin releasing hormone (CRH). HP5 mice exhibited attenuated corticosterone responses upon a restraint stress test and inflammatory stress following LPS injection, as well as increased anxiety-like and depressive-like behavior on open field and forced swim tests. Pituitary corticotroph CRH receptor subtype 1 (CRHR1) mRNA expression and ACTH responses to CRH were also attenuated in HP5 mice. In AtT20 cells stably overexpressing SSTR5, CRHR1 expression and cAMP response to CRH were reduced, whereas both were increased after SSTR5 KO. In elucidating mechanisms for these observations, we show that SSTR5-induced miR-449c suppresses both CRHR1 expression and function. We conclude that corticotroph SSTR5 attenuates HPA axis responses via CRHR1 downregulation, suggesting a role for SSTR5 in the pathogenesis of secondary adrenal insufficiency.
Endocrinology; Neuroendocrine regulation; growth factors