PMC:3724972 / 4137-6802
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3724972","sourcedb":"PMC","sourceid":"3724972","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3724972","text":"Somatostatin receptors in the pituitary and pituitary adenomas\nSomatostatin often serves to inhibit secretory responses, but also exhibits antiproliferative effects in some tissues [14]. Somatostatin receptors are widespread throughout the central nervous system and in several peripheral tissues [15, 16]. To date, 5 somatostatin receptor subtypes (sstr) have been identified and cloned (sstr1–sstr5) [14]. Immunostaining indicates that normal human anterior pituitary expresses all 5 subtypes, and that most corticotroph adenomas express ≥1 sstr [17–19]. While expression levels are highly variable, sstr2 and sstr5 are most consistently expressed, and sstr4 is generally absent [17, 19]. A study using quantitative RT-PCR and immunohistochemistry found that human corticotroph adenomas expressed sstr1,2,4 and 5, and that sstr5 had the highest expression levels in 10/12 adenomas [20].\nDifferential sstr expression levels between somatotroph and corticotroph adenomas may partly explain why octreotide, which has relative selectivity for sstr2, inhibits growth hormone secretion from somatotroph adenomas but has little effect on ACTH secretion from corticotroph adenomas [19]. Somatostatin has also been shown to inhibit ACTH secretion from pituitary cells taken from adrenalectomized rats [21], and reduced serum ACTH levels in humans who had hypocortisolism [22–24], but did not affect ACTH secretion from pituitary cells taken from normal rats [25, 26] or ACTH levels in patients with CD [17, 19, 27–29]. These findings suggested that high corticosteroid levels were associated with low responsiveness to sstr2-specific analogs in corticotroph adenomas. This conclusion is supported by the observation that the ability of somatostatin or octreotide to inhibit ACTH secretion from cultured corticotroph adenoma cells was abolished by pretreatment with dexamethasone [30].\nThese findings have produced a working model of the regulation of ACTH secretion by corticotroph adenomas [31, 32], wherein high systemic cortisol downregulates sstr2 expression in the corticotroph adenoma cells, rendering sstr2 agonists ineffective at inhibiting ACTH secretion. In contrast, sstr5 expression appears to be relatively unaffected by high cortisol levels. Upon treatment with an sstr5 agonist, ACTH secretion is reduced, leading to declines in cortisol secretion from the adrenal glands. This model is supported by evidence from murine AtT20 cells, a corticotroph cell line. Treatment of AtT20 cells with dexamethasone reduced expression of sstr2 mRNA without significantly affecting sstr5 mRNA expression or the ability of an sstr5 agonist to inhibit ACTH secretion [33].","divisions":[{"label":"title","span":{"begin":0,"end":62}},{"label":"p","span":{"begin":63,"end":888}},{"label":"p","span":{"begin":889,"end":1877}}],"tracks":[{"project":"2_test","denotations":[{"id":"23673515-10433861-63233585","span":{"begin":182,"end":184},"obj":"10433861"},{"id":"23673515-8243278-63233586","span":{"begin":298,"end":300},"obj":"8243278"},{"id":"23673515-12502754-63233587","span":{"begin":302,"end":304},"obj":"12502754"},{"id":"23673515-10433861-63233588","span":{"begin":403,"end":405},"obj":"10433861"},{"id":"23673515-15281350-63233589","span":{"begin":549,"end":551},"obj":"15281350"},{"id":"23673515-22976314-63233589","span":{"begin":549,"end":551},"obj":"22976314"},{"id":"23673515-15817922-63233589","span":{"begin":549,"end":551},"obj":"15817922"},{"id":"23673515-15281350-63233590","span":{"begin":682,"end":684},"obj":"15281350"},{"id":"23673515-15817922-63233591","span":{"begin":686,"end":688},"obj":"15817922"},{"id":"23673515-16940446-63233592","span":{"begin":884,"end":886},"obj":"16940446"},{"id":"23673515-15817922-63233593","span":{"begin":1176,"end":1178},"obj":"15817922"},{"id":"23673515-20545-63233594","span":{"begin":1295,"end":1297},"obj":"20545"},{"id":"23673515-1256005-63233595","span":{"begin":1365,"end":1367},"obj":"1256005"},{"id":"23673515-2543178-63233595","span":{"begin":1365,"end":1367},"obj":"2543178"},{"id":"23673515-166089-63233595","span":{"begin":1365,"end":1367},"obj":"166089"},{"id":"23673515-6143656-63233596","span":{"begin":1452,"end":1454},"obj":"6143656"},{"id":"23673515-2865690-63233597","span":{"begin":1456,"end":1458},"obj":"2865690"},{"id":"23673515-15281350-63233598","span":{"begin":1496,"end":1498},"obj":"15281350"},{"id":"23673515-15817922-63233599","span":{"begin":1500,"end":1502},"obj":"15817922"},{"id":"23673515-1973178-63233600","span":{"begin":1504,"end":1506},"obj":"1973178"},{"id":"23673515-8935599-63233600","span":{"begin":1504,"end":1506},"obj":"8935599"},{"id":"23673515-2160871-63233600","span":{"begin":1504,"end":1506},"obj":"2160871"},{"id":"23673515-8130885-63233601","span":{"begin":1873,"end":1875},"obj":"8130885"},{"id":"23673515-18221833-63233602","span":{"begin":1985,"end":1987},"obj":"18221833"},{"id":"23673515-17413188-63233603","span":{"begin":1989,"end":1991},"obj":"17413188"},{"id":"23673515-15769796-63233604","span":{"begin":2661,"end":2663},"obj":"15769796"}],"attributes":[{"subj":"23673515-10433861-63233585","pred":"source","obj":"2_test"},{"subj":"23673515-8243278-63233586","pred":"source","obj":"2_test"},{"subj":"23673515-12502754-63233587","pred":"source","obj":"2_test"},{"subj":"23673515-10433861-63233588","pred":"source","obj":"2_test"},{"subj":"23673515-15281350-63233589","pred":"source","obj":"2_test"},{"subj":"23673515-22976314-63233589","pred":"source","obj":"2_test"},{"subj":"23673515-15817922-63233589","pred":"source","obj":"2_test"},{"subj":"23673515-15281350-63233590","pred":"source","obj":"2_test"},{"subj":"23673515-15817922-63233591","pred":"source","obj":"2_test"},{"subj":"23673515-16940446-63233592","pred":"source","obj":"2_test"},{"subj":"23673515-15817922-63233593","pred":"source","obj":"2_test"},{"subj":"23673515-20545-63233594","pred":"source","obj":"2_test"},{"subj":"23673515-1256005-63233595","pred":"source","obj":"2_test"},{"subj":"23673515-2543178-63233595","pred":"source","obj":"2_test"},{"subj":"23673515-166089-63233595","pred":"source","obj":"2_test"},{"subj":"23673515-6143656-63233596","pred":"source","obj":"2_test"},{"subj":"23673515-2865690-63233597","pred":"source","obj":"2_test"},{"subj":"23673515-15281350-63233598","pred":"source","obj":"2_test"},{"subj":"23673515-15817922-63233599","pred":"source","obj":"2_test"},{"subj":"23673515-1973178-63233600","pred":"source","obj":"2_test"},{"subj":"23673515-8935599-63233600","pred":"source","obj":"2_test"},{"subj":"23673515-2160871-63233600","pred":"source","obj":"2_test"},{"subj":"23673515-8130885-63233601","pred":"source","obj":"2_test"},{"subj":"23673515-18221833-63233602","pred":"source","obj":"2_test"},{"subj":"23673515-17413188-63233603","pred":"source","obj":"2_test"},{"subj":"23673515-15769796-63233604","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ece693","default":true}]}]}}