Pituitary Pathology and Gene Expression in Acromegalic Cats

Overview

Journal J Endocr Soc

Specialty Endocrinology

Date 2019 Jan 9

PMID 30620005

Citations 14

Authors

Christopher J Scudder

Samantha M Mirczuk

Karen M Richardson

Victoria J Crossley

Jacob T C Regan

Ruth Gostelow

Yaiza Forcada

Katarina Hazuchova

Norelene Harrington

Imelda M McGonnell

David B Church

Patrick J Kenny

Marta Korbonits

Robert C Fowkes

Stijn J M Niessen

Affiliations

Soon will be listed here.

Abstract

The prevalence of GH-secreting pituitary tumors in domestic cats () is 10-fold greater than in humans. The predominant inhibitory receptors of GH-secreting pituitary tumors are somatostatin receptors (SSTRs) and D dopamine receptor (DRD2). The expression of these receptors is associated with the response to somatostatin analog and dopamine agonist treatment in human patients with acromegaly. The aim of this study was to describe pathological features of pituitaries from domestic cats with acromegaly, pituitary receptor expression, and investigate correlates with clinical data, including pituitary volume, time since diagnosis of diabetes, insulin requirement, and serum IGF1 concentration. Loss of reticulin structure was identified in 15 of 21 pituitaries, of which 10 of 15 exhibited acinar hyperplasia. , , , and mRNA were identified in the feline pituitary whereas and were not. Expression of , , and was greater in acromegalic cats compared with controls. A negative correlation was identified between mRNA expression and pituitary volume. The loss of DRD2 expression should be investigated as a mechanism allowing the development of larger pituitary tumors.

Citing Articles

Expression of somatostatin receptors in canine and feline meningioma.

Immler M, Wolfram M, Oevermann A, Walter I, Wolfesberger B, Tichy A Vet Med Sci. 2024; 10(4):e1537.

PMID: 39011594 PMC: 11250153. DOI: 10.1002/vms3.1537.

Hepatic Gene Expression of Angiogenic and Regeneration Markers in Cats with Congenital Portosystemic Shunts (CPSS).

Tivers M, Mirczuk S, Charlesworth A, Wood L, Barker E, Lipscomb V Vet Sci. 2024; 11(3).

PMID: 38535834 PMC: 10974408. DOI: 10.3390/vetsci11030100.

Feline Comorbidities: Hypersomatotropism-induced diabetes in cats.

Scudder C, Church D J Feline Med Surg. 2024; 26(2):1098612X241226690.

PMID: 38323402 PMC: 10911310. DOI: 10.1177/1098612X241226690.

Transsphenoidal hypophysectomy for the treatment of hypersomatotropism secondary to a pituitary somatotroph adenoma in a dog.

Steele M, Lawson J, Scudder C, Watson A, Ho N, Yaffy D J Vet Intern Med. 2023; 38(1):351-357.

PMID: 37916616 PMC: 10800194. DOI: 10.1111/jvim.16929.

Quality of life and response to treatment in cats with hypersomatotropism: the owners' point of view.

Corsini A, Niessen S, Miceli D, Caney S, Zeugswetter F, Sieber-Ruckstuhl N J Feline Med Surg. 2022; 24(8):e175-e182.

PMID: 35616046 PMC: 10812257. DOI: 10.1177/1098612X221098718.

References

Corbetta S, Ballare E, Mantovani G, Lania A, Losa M, Di Blasio A . Somatostatin receptor subtype 2 and 5 in human GH-secreting pituitary adenomas: analysis of gene sequence and mRNA expression. Eur J Clin Invest. 2001; 31(3):208-14. DOI: 10.1046/j.1365-2362.2001.00786.x. View

Niessen S, Forcada Y, Mantis P, Lamb C, Harrington N, Fowkes R . Studying Cat (Felis catus) Diabetes: Beware of the Acromegalic Imposter. PLoS One. 2015; 10(5):e0127794. PMC: 4449218. DOI: 10.1371/journal.pone.0127794. View

Pisarek H, Pawlikowski M, Kunert-Radek J, Radek M . Expression of somatostatin receptor subtypes in human pituitary adenomas -- immunohistochemical studies. Endokrynol Pol. 2009; 60(4):240-51. View

Scudder C, Gostelow R, Forcada Y, Schmid H, Church D, Niessen S . Pasireotide for the Medical Management of Feline Hypersomatotropism. J Vet Intern Med. 2015; 29(4):1074-80. PMC: 4895359. DOI: 10.1111/jvim.12608. View

Scudder C, Mirczuk S, Richardson K, Crossley V, Regan J, Gostelow R . Pituitary Pathology and Gene Expression in Acromegalic Cats. J Endocr Soc. 2019; 3(1):181-200. PMC: 6316999. DOI: 10.1210/js.2018-00226. View

Syro L, Rotondo F, Serna C, Ortiz L, Kovacs K . Pathology of GH-producing pituitary adenomas and GH cell hyperplasia of the pituitary. Pituitary. 2016; 20(1):84-92. DOI: 10.1007/s11102-016-0748-8. View

Zatelli M, Piccin D, Tagliati F, Bottoni A, Ambrosio M, Margutti A . Dopamine receptor subtype 2 and somatostatin receptor subtype 5 expression influences somatostatin analogs effects on human somatotroph pituitary adenomas in vitro. J Mol Endocrinol. 2005; 35(2):333-41. DOI: 10.1677/jme.1.01876. View

Kopchick J, Bellush L, Coschigano K . Transgenic models of growth hormone action. Annu Rev Nutr. 1999; 19:437-61. DOI: 10.1146/annurev.nutr.19.1.437. View

Scacchi M, Cavagnini F . Acromegaly. Pituitary. 2006; 9(4):297-303. DOI: 10.1007/s11102-006-0409-4. View

10.

Gadelha M, Wildemberg L, Bronstein M, Gatto F, Ferone D . Somatostatin receptor ligands in the treatment of acromegaly. Pituitary. 2017; 20(1):100-108. DOI: 10.1007/s11102-017-0791-0. View

11.

Lupp A, Nagel F, Doll C, Rocken C, Evert M, Mawrin C . Reassessment of sst3 somatostatin receptor expression in human normal and neoplastic tissues using the novel rabbit monoclonal antibody UMB-5. Neuroendocrinology. 2012; 96(4):301-10. DOI: 10.1159/000337659. View

12.

Wildemberg L, Vieira Neto L, Costa D, Nasciutti L, Takiya C, Alves L . Validation of immunohistochemistry for somatostatin receptor subtype 2A in human somatotropinomas: comparison between quantitative real time RT-PCR and immunohistochemistry. J Endocrinol Invest. 2011; 35(6):580-4. DOI: 10.3275/7906. View

13.

Schulz S, Schmitt J, Wiborny D, Schmidt H, Olbricht S, Weise W . Immunocytochemical detection of somatostatin receptors sst1, sst2A, sst2B, and sst3 in paraffin-embedded breast cancer tissue using subtype-specific antibodies. Clin Cancer Res. 1998; 4(9):2047-52. View

14.

Mercado M, Borges F, Bouterfa H, Chang T, Chervin A, Farrall A . A prospective, multicentre study to investigate the efficacy, safety and tolerability of octreotide LAR (long-acting repeatable octreotide) in the primary therapy of patients with acromegaly. Clin Endocrinol (Oxf). 2007; 66(6):859-68. PMC: 1974838. DOI: 10.1111/j.1365-2265.2007.02825.x. View

15.

Villa C, Lagonigro M, Magri F, Koziak M, Jaffrain-Rea M, Brauner R . Hyperplasia-adenoma sequence in pituitary tumorigenesis related to aryl hydrocarbon receptor interacting protein gene mutation. Endocr Relat Cancer. 2011; 18(3):347-56. DOI: 10.1530/ERC-11-0059. View

16.

Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A . Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002; 3(7):RESEARCH0034. PMC: 126239. DOI: 10.1186/gb-2002-3-7-research0034. View

17.

Katznelson L, Laws Jr E, Melmed S, Molitch M, Murad M, Utz A . Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014; 99(11):3933-51. DOI: 10.1210/jc.2014-2700. View

18.

Ferone D, de Herder W, Pivonello R, Kros J, Van Koetsveld P, de Jong T . Correlation of in vitro and in vivo somatotropic adenoma responsiveness to somatostatin analogs and dopamine agonists with immunohistochemical evaluation of somatostatin and dopamine receptors and electron microscopy. J Clin Endocrinol Metab. 2008; 93(4):1412-7. DOI: 10.1210/jc.2007-1358. View

19.

Casarini A, Jallad R, Pinto E, Soares I, Nonogaki S, Giannella-Neto D . Acromegaly: correlation between expression of somatostatin receptor subtypes and response to octreotide-lar treatment. Pituitary. 2009; 12(4):297-303. DOI: 10.1007/s11102-009-0175-1. View

20.

Raitila A, Lehtonen H, Arola J, Heliovaara E, Ahlsten M, Georgitsi M . Mice with inactivation of aryl hydrocarbon receptor-interacting protein (Aip) display complete penetrance of pituitary adenomas with aberrant ARNT expression. Am J Pathol. 2010; 177(4):1969-76. PMC: 2947291. DOI: 10.2353/ajpath.2010.100138. View