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Comparative distribution of somatostatin and somatostatin receptors in PTU-induced hypothyroidism

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Abstract

Purpose

Propylthiouracil (PTU)-induced hypothyroidism is a well-established model for assessing hormonal and morphological changes in thyroid as well as other central and peripheral tissues. Somatostatin (SST) is known to regulate hormonal secretion and synthesis in endocrine tissues; however, nothing is currently known about the distribution of SST and its receptor in hypothyroidism.

Method

In the present study, the comparative immunohistochemical distribution of SST and somatostatin receptors (SSTRs) were analyzed in PTU-induced hypothyroid rats. Rats were treated with PTU for 15 days followed by a co-administration of levothyroxine (LVT) for 15 days. After PTU and LVT treatments (day 30), rats were further administered LVT alone for 15 more days (day 45). The subcellular distribution of SST and SSTR subtypes was determined by peroxidase immunohistochemistry in the thyroid gland collected from control and treated rats.

Results

SST and SSTR subtypes were found to be moderately expressed in control thyroid tissues. SST and SSTR subtypes like immunoreactivity increased significantly in follicular and parafollicular epithelial cells in the thyroid of PTU-treated rats. The PTU-induced changes in the expression of SST and SSTR subtypes were suppressed by the administration of the LVT. In addition to thyroid tissues, SST and SSTRs expression was also changed in non-follicular tissues including blood vessels, smooth muscle cells, and connective tissue following treatments.

Conclusion

The present study revealed a distinct subcellular distribution of SST and SSTR subtypes in the thyroid and provides a new insight for the role of SST and SSTR subtypes in hypothyroidism in addition to its well-established role in negative regulation of hormonal secretion.

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Abbreviations

D2R:

Dopamine receptor 2

GH:

Growth hormones

LVT:

Levothyroxine

PTU:

Propylthiouracil

SST:

Somatostatin

SSTR:

Somatostatin receptor

SRIF:

Somatotropin-release inhibiting factor

T3:

Triiodothyronine

TSH:

Thyroid-stimulating hormone

TRH:

Thyroid-releasing hormone

T4:

Thyroxine

5′-DI:

5′-Iodothyroine monodeiodinse

References

  1. B.B. Mughal, J.B. Fini, B.A. Demeneix, Thyroid-disrupting chemicals and brain development: an update. Endocr. Connect. 7(4), R160–R186 (2018). https://doi.org/10.1530/EC-18-0029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. C. Chen, Z. Xie, Y. Shen, S.F. Xia, The roles of thyroid and thyroid hormone in pancreas: physiology and pathology. Int. J. Endocrinol. 2018, 2861034 (2018). https://doi.org/10.1155/2018/2861034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. O. Tarim, Thyroid hormones and growth in health and disease. J. Clin. Res. Pediatr. Endocrinol. 3(2), 51–55 (2011). https://doi.org/10.4274/jcrpe.v3i2.11

    Article  PubMed  PubMed Central  Google Scholar 

  4. M.P. Vanderpump, The epidemiology of thyroid disease. Br. Med. Bull. 99, 39–51 (2011). https://doi.org/10.1093/bmb/ldr030

    Article  PubMed  Google Scholar 

  5. H. Katakami, T.R. Downs, L.A. Frohman, Decreased hypothalamic growth hormone-releasing hormone content and pituitary responsiveness in hypothyroidism. J. Clin. Investig. 77(5), 1704–1711 (1986). https://doi.org/10.1172/JCI112490

    Article  CAS  PubMed  Google Scholar 

  6. M. Sato, J. Takahara, Y. Fujioka, M. Niimi, S. Irino, Physiological role of growth hormone (GH)-releasing factor and somatostatin in the dynamics of GH secretion in adult male rat. Endocrinology 123(4), 1928–1933 (1988). https://doi.org/10.1210/endo-123-4-1928

    Article  CAS  PubMed  Google Scholar 

  7. Y.C. Patel, Somatostatin and its receptor family. Front. Neuroendocrinol. 20(3), 157–198 (1999). https://doi.org/10.1006/frne.1999.0183

    Article  CAS  PubMed  Google Scholar 

  8. P. Brazeau, W. Vale, R. Burgus, N. Ling, M. Butcher, J. Rivier, R. Guillemin, Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 179(4068), 77–79 (1973). https://doi.org/10.1126/science.179.4068.77

    Article  CAS  PubMed  Google Scholar 

  9. U. Kumar, R. Sasi, S. Suresh, A. Patel, M. Thangaraju, P. Metrakos, S.C. Patel, Y.C. Patel, Subtype-selective expression of the five somatostatin receptors (hSSTR1-5) in human pancreatic islet cells: a quantitative double-label immunohistochemical analysis. Diabetes 48(1), 77–85 (1999). https://doi.org/10.2337/diabetes.48.1.77

    Article  CAS  PubMed  Google Scholar 

  10. C. Bruns, G. Weckbecker, F. Raulf, K. Kaupmann, P. Schoeffter, D. Hoyer, H. Lubbert, Molecular pharmacology of somatostatin-receptor subtypes. Ann. N. Y. Acad. Sci. 733, 138–146 (1994). https://doi.org/10.1111/j.1749-6632.1994.tb17263.x

    Article  CAS  PubMed  Google Scholar 

  11. R. Danesi, C. Agen, U. Benelli, A.D. Paolo, D. Nardini, G. Bocci, F. Basolo, A. Campagni, M.D. Tacca, Inhibition of experimental angiogenesis by the somatostatin analogue octreotide acetate (SMS 201-995). Clin. Cancer Res. 3(2), 265–272 (1997)

    CAS  PubMed  Google Scholar 

  12. U. Kumar, M. Grant, Somatostatin and somatostatin receptors. Results Probl. Cell Differ. 50, 137–184 (2010). https://doi.org/10.1007/400_2009_29

    Article  CAS  PubMed  Google Scholar 

  13. A. Schonbrunn, H. Tashjian Jr, Characterization of functional receptors for somatostatin in rat pituitary cells in culture. J. Biol. Chem. 253(18), 6473–6483 (1978)

    CAS  PubMed  Google Scholar 

  14. M. Vanetti, M. Kouba, X. Wang, G. Vogt, V. Hollt, Cloning and expression of a novel mouse somatostatin receptor (SSTR2B). FEBS Lett. 311(3), 290–294 (1992). https://doi.org/10.1016/0014-5793(92)81122-3

    Article  CAS  PubMed  Google Scholar 

  15. K. Sharma, Y.C. Patel, C.B. Srikant, Subtype-selective induction of wild-type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3. Mol. Endocrinol. 10(12), 1688–1696 (1996). https://doi.org/10.1210/mend.10.12.8961277

    Article  CAS  PubMed  Google Scholar 

  16. Z. Helyes, E. Pinter, K. Sandor, K. Elekes, A. Banvolgyi, D. Keszthelyi, E. Szoke, D.M. Toth, Z. Sandor, L. Kereskai, G. Pozsgai, J.P. Allen, P.C. Emson, A. Markovics, J. Szolcsanyi, Impaired defense mechanism against inflammation, hyperalgesia, and airway hyperreactivity in somatostatin 4 receptor gene-deleted mice. Proc. Natl Acad. Sci. USA 106(31), 13088–13093 (2009). https://doi.org/10.1073/pnas.0900681106

    Article  PubMed  Google Scholar 

  17. J.L. Ramirez, M. Grant, M. Norman, X.P. Wang, S. Moldovan, F.J. de Mayo, C. Brunicardi, U. Kumar, Deficiency of somatostatin (SST) receptor type 5 (SSTR5) is associated with sexually dimorphic changes in the expression of SST and SST receptors in brain and pancreas. Mol. Cell. Endocrinol. 221(1-2), 105–119 (2004). https://doi.org/10.1016/j.mce.2004.02.001

    Article  CAS  PubMed  Google Scholar 

  18. U. Kumar, Colocalization of somatostatin receptor subtypes (SSTR1-5) with somatostatin, NADPH-diaphorase (NADPH-d), and tyrosine hydroxylase in the rat hypothalamus. J. Comp. Neurol. 504(2), 185–205 (2007). https://doi.org/10.1002/cne.21444

    Article  CAS  PubMed  Google Scholar 

  19. U. Kumar, S.I. Grigorakis, H.L. Watt, R. Sasi, L. Snell, P. Watson, S. Chaudhari, Somatostatin receptors in primary human breast cancer: quantitative analysis of mRNA for subtypes 1-5 and correlation with receptor protein expression and tumor pathology. Breast Cancer Res. Treat. 92(2), 175–186 (2005). https://doi.org/10.1007/s10549-005-2414-0

    Article  CAS  PubMed  Google Scholar 

  20. U. Kumar, D. Laird, C.B. Srikant, E. Escher, Y.C. Patel, Expression of the five somatostatin receptor (SSTR1-5) subtypes in rat pituitary somatotrophes: quantitative analysis by double-layer immunofluorescence confocal microscopy. Endocrinology 138(10), 4473–4476 (1997). https://doi.org/10.1210/endo.138.10.5566

    Article  CAS  PubMed  Google Scholar 

  21. S. Panda, A. Khar, Possible amelioration of hyperthyroidism by the leaf extract of Annona squamosa. Curr. Sci. 84, 1402–1404 (2003)

    Google Scholar 

  22. F. Varghese, A.B. Bukhari, R. Malhotra, A. De, IHC Profiler: an open source plugin for the quantitative evaluation and automated scoring of immunohistochemistry images of human tissue samples. PloS ONE. 9(5), e96801 (2014). https://doi.org/10.1371/journal.pone.0096801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. E. Cano-Europa, V. Blas-Valdivia, M. Franco-Colin, C.A. Gallardo-Casas, R. Ortiz-Butron, Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney. Acta. Histochem. 113(1), 1–5 (2011). https://doi.org/10.1016/j.acthis.2009.07.004

    Article  CAS  PubMed  Google Scholar 

  24. M. Mohibbullah, K.M.I. Bashir, S.K. Kim, Y.K. Hong, A. Kim, S.K. Ku, J.S. Choi. Protective effects of a mixed plant extracts derived from Astragalus membranaceus and Laminaria japonica on PTU-induced hypothyroidism and liver damages. J. Food Biochem. 43(7), e12853 (2019). https://doi.org/10.1111/jfbc.12853

  25. J.H. Hwang, H.W. Jung, S.Y. Kang, A.N. Kang, J.N. Ma, X.L. Meng, M.S. Hwang, Y.K. Park, Therapeutic effects of acupuncture with MOK, a polyherbal medicine, on PTU-induced hypothyroidism in rats. Exp. Ther. Med 16(1), 310–320 (2018). https://doi.org/10.3892/etm.2018.6190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. F. Asiaei, A. Fazel, A.A. Rajabzadeh, M. Hosseini, F. Beheshti, M. Seghatoleslam, Neuroprotective effects of Nigella sativa extract upon the hippocampus in PTU-induced hypothyroidism juvenile rats: a stereological study. Metab. Brain Dis. 32(5), 1755–1765 (2017). https://doi.org/10.1007/s11011-017-0025-1

    Article  CAS  PubMed  Google Scholar 

  27. S. Bhanja, G.B.N. Chainy, PTU-induced hypothyroidism modulates antioxidant defence status in the developing cerebellum. Int J. Dev. Neurosci. 28(3), 251–262 (2010). https://doi.org/10.1016/j.ijdevneu.2010.01.005

    Article  CAS  PubMed  Google Scholar 

  28. R. Wilen, C.H. Bastomsky, F. Naftolin, Control of puberty in female rats—the effect of Ptu-Induced hypothyroidism and systematic undernutrition. Pediatr. Res 15(2), 169–171 (1981). https://doi.org/10.1203/00006450-198102000-00019

    Article  CAS  PubMed  Google Scholar 

  29. C. Lucke, B. Hoffken, A. von zur Muhlen, The effect of somatostatin on TSH levels in patients with primary hypothyroidism. J. Clin. Endocrinol. Metab. 41(06), 1082–1084 (1975). https://doi.org/10.1210/jcem-41-6-1082

    Article  CAS  PubMed  Google Scholar 

  30. S.W. Lamberts, J. Zuyderwijk, F. den Holder, P. van Koetsveld, L. Hofland, Studies on the conditions determining the inhibitory effect of somatostatin on adrenocorticotropin, prolactin and thyrotropin release by cultured rat pituitary cells. Neuroendocrinology 50(1), 44–50 (1989). https://doi.org/10.1159/000125200

    Article  CAS  PubMed  Google Scholar 

  31. J. Weeke, A.P. Hansen, K. Lundaek, Inhibition by somatostatin of basal levels of serum thyrotropin (TSH) in normal men. J. Clin. Endocrinol. Metab. 41(1), 168–171 (1975). https://doi.org/10.1210/jcem-41-1-168

    Article  CAS  PubMed  Google Scholar 

  32. S. Mariotti, P. Beck-Peccoz. Physiology of the hypothalamic-pituitary-thyroid axis. In: K.R. Feingold, B. Anawalt, A. Boyce, G. Chrousos, K. Dungan, A. Grossman, J.M. Hershman, G. Kaltsas, C. Koch, P. Kopp, M. Korbonits, R. McLachlan, J.E. Morley, M. New, L. Perreault, J. Purnell, R. Rebar, F. Singer, D.L. Trence, A. Vinik, D.P. Wilson. (eds.) Endotext. South Dartmouth (MA) (2000)

  33. A. Arimura, A.V. Schally, Increase in basal and thyrotropin-releasing hormone (TRH)-stimulated secretion of thyrotropin (TSH) by passive immunization with antiserum to somatostatin in rats. Endocrinology 98(4), 1069–1072 (1976). https://doi.org/10.1210/endo-98-4-1069

    Article  CAS  PubMed  Google Scholar 

  34. I. Yang, J. Woo, S. Kim, J. Kim, Y. Kim, Y. Choi, Suppression of TRH-stimulated TSH secretion by glucose-induced hypothalamic somatostatin release. Horm. Metab. Res. 28(10), 553–557 (1996). https://doi.org/10.1055/s-2007-979851

    Article  CAS  PubMed  Google Scholar 

  35. M. Berelowitz, K. Maeda, S. Harris, L.A. Frohman, The effect of alterations in the pituitary-thyroid axis on hypothalamic content and in vitro release of somatostatin-like immunoreactivity. Endocrinology 107(1), 24–29 (1980). https://doi.org/10.1210/endo-107-1-24

    Article  CAS  PubMed  Google Scholar 

  36. S. Skare, K.F. Hanssen, N. Norman, Plasma somatostatin is elevated in primary hypothyroidism compared with hyperthyroidism. Acta Endocrinol. Cop. 111(3), 331–335 (1986). https://doi.org/10.1530/acta.0.1110331

    Article  CAS  Google Scholar 

  37. K.B. Ain, K.D. Taylor, S. Tofiq, G. Venkataraman, Somatostatin receptor subtype expression in human thyroid and thyroid carcinoma cell lines. J. Clin. Endocrinol. Metab. 82(6), 1857–1862 (1997). https://doi.org/10.1210/jcem.82.6.4013

    Article  CAS  PubMed  Google Scholar 

  38. D. Hoyer, G.I. Bell, M. Berelowitz, J. Epelbaum, W. Feniuk, P.P. Humphrey, A.M. O’Carroll, Y.C. Patel, A. Schonbrunn, J.E. Taylor et al. Classification and nomenclature of somatostatin receptors. Trends Pharmacol. Sci. 16(3), 86–88 (1995)

    Article  CAS  Google Scholar 

  39. C. Scarpignato, I. Pelosini, Somatostatin analogs for cancer treatment and diagnosis: an overview. Chemotherapy 47(Suppl 2), 1–29 (2001). https://doi.org/10.1159/000049157

    Article  CAS  PubMed  Google Scholar 

  40. H. Pisarek, T. Stepien, R. Kubiak, E. Borkowska, M. Pawlikowski, Expression of somatostatin receptor subtypes in human thyroid tumors: the immunohistochemical and molecular biology (RT-PCR) investigation. Thyroid Res. 2(1), 1 (2009). https://doi.org/10.1186/1756-6614-2-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. H. Pisarek, M. Pawlikowski, M. Marchlewska, R. Minias, K. Winczyk, An immunohistochemical investigation of the expression of somatostatin receptor subtypes - should therapeutic trials be performed to determine the efficacy of somatostatin analogs in treating advanced thyroid malignances? Exp. Clin. Endocrinol. Diabetes. 123(6), 342–346 (2015). https://doi.org/10.1055/s-0035-1548825

    Article  CAS  PubMed  Google Scholar 

  42. F. Sundler, J. Alumets, R. Hakanson, L. Bjorklund, O. Ljungberg, Somatostatin-immunoreactive cells in medullary carcinoma of the thyroid. Am. J. Pathol. 88(2), 381–386 (1977)

    CAS  PubMed  PubMed Central  Google Scholar 

  43. T. Hokfelt, S. Efendic, C. Hellerstrom, O. Johansson, R. Luft, A. Arimura, Cellular localization of somatostatin in endocrine-like cells and neurons of the rat with special references to the A1-cells of the pancreatic islets and to the hypothalamus. Acta Endocrinologica. Supplementum 200, 5–41 (1975)

    Article  CAS  Google Scholar 

  44. J.A. Parsons, S.L. Erlandsen, O.D. Hegre, R.C. McEvoy, R.P. Elde, Central and peripheral localization of somatostatin. Immunoenzyme immunocytochemical studies. J. Histochem. Cytochem. 24(7), 872–882 (1976). https://doi.org/10.1177/24.7.60436

    Article  CAS  PubMed  Google Scholar 

  45. I. Shimon, J.E. Taylor, J.Z. Dong, R.A. Bitonte, S. Kim, B. Morgan, D.H. Coy, M.D. Culler, S. Melmed, Somatostatin receptor subtype specificity in human fetal pituitary cultures—differential role of SSTR2 and SSTR5 for growth hormone, thyroid-stimulating hormone, and prolactin regulation. J. Clin. Investig. 99(4), 789–798 (1997). https://doi.org/10.1172/Jci119225

    Article  CAS  PubMed  Google Scholar 

  46. B. De Groef, K.L. Geris, J. Manzano, J. Bernal, R.P. Millar, A.B. Abou-Samra, T.E. Porter, A. Iwasawa, E.R. Kuhn, V.M. Darras, Involvement of thyrotropin-releasing hormone receptor, somatostatin receptor subtype 2 and corticotropin-releasing hormone receptor type 1 in the control of chicken thyrotropin secretion. Mol. Cell. Endocrinol. 203(1–2), 33–39 (2003). https://doi.org/10.1016/S0303-7207(03)00120-5

    Article  CAS  PubMed  Google Scholar 

  47. M. Papotti, U. Kumar, M. Volante, C. Pecchioni, Y.C. Patel, Immunohistochemical detection of somatostatin receptor types 1-5 in medullary carcinoma of the thyroid. Clin. Endocrinol. 54(5), 641–649 (2001)

    Article  CAS  Google Scholar 

  48. R.C. Patel, U. Kumar, D.C. Lamb, J.S. Eid, M. Rocheville, M. Grant, A. Rani, T. Hazlett, S.C. Patel, E. Gratton, Y.C. Patel, Ligand binding to somatostatin receptors induces receptor-specific oligomer formation in live cells. Proc. Natl Acad. Sci. USA 99(5), 3294–3299 (2002). https://doi.org/10.1073/pnas.042705099

    Article  CAS  PubMed  Google Scholar 

  49. H. Atkinson, J.A. England, A. Rafferty, V. Jesudason, K. Bedford, L. Karsai, S.L. Atkin, Somatostatin receptor expression in thyroid disease. Int. J. Exp. Pathol. 94(3), 226–229 (2013). https://doi.org/10.1111/iep.12024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Y. Taniyama, T. Suzuki, Y. Mikami, T. Moriya, S. Satomi, H. Sasano, Systemic distribution of somatostatin receptor subtypes in human: an immunohistochemical study. Endocr. J. 52(5), 605–611 (2005). https://doi.org/10.1507/endocrj.52.605

    Article  CAS  PubMed  Google Scholar 

  51. Y. Fujii, T. Gonoi, Y. Yamada, K. Chihara, N. Inagaki, S. Seino, Somatostatin receptor subtype SSTR2 mediates the inhibition of high-voltage-activated calcium channels by somatostatin and its analogue SMS 201-995. FEBS Lett. 355(2), 117–120 (1994). https://doi.org/10.1016/0014-5793(94)01159-1

    Article  CAS  PubMed  Google Scholar 

  52. A.F. Abdel-Magid, Treating pain with somatostatin receptor subtype 4 agonists. ACS Med. Chem. Lett. 6(2), 110–111 (2015). https://doi.org/10.1021/ml500538a

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. R.K. Somvanshi, U. Kumar, delta-opioid receptor and somatostatin receptor-4 heterodimerization: possible implications in modulation of pain associated signaling. PloS ONE 9(1), e85193 (2014). https://doi.org/10.1371/journal.pone.0085193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Z. Varecza, K. Elekes, T. Laszlo, A. Perkecz, E. Pinter, Z. Sandor, J. Szolcsanyi, D. Keszthelyi, A. Szabo, K. Sandor, T.F. Molnar, Z. Szanto, J.E. Pongracz, Z. Helyes. Expression of the somatostatin receptor subtype 4 in intact and inflamed pulmonary tissues. J. Histochem. Cytochem. 57(12), 1127–1137 (2009). https://doi.org/10.1369/jhc.2009.953919.

  55. T. Endo, T. Saito, T. Uchida, T. Onaya, Effects of somatostatin and serotonin on calcitonin secretion from cultured rat parafollicular cells. Acta Endocrinol. (Copenh) 117(2), 214–218 (1988). https://doi.org/10.1530/acta.0.1170214

    Article  CAS  Google Scholar 

  56. E. Mato, X. Matias-Guiu, A. Chico, S.M. Webb, R. Cabezas, L. Berna, A. De Leiva, Somatostatin and somatostatin receptor subtype gene expression in medullary thyroid carcinoma. J. Clin. Endocrinol. Metab. 83(7), 2417–2420 (1998). https://doi.org/10.1210/jcem.83.7.4955

    Article  CAS  PubMed  Google Scholar 

  57. S. Reichlin, Somatostatin .1. N. Engl. J. Med 309(24), 1495–1501 (1983). https://doi.org/10.1056/Nejm198312153092406

    Article  CAS  PubMed  Google Scholar 

  58. S. Van Noorden, J.M. Polak, A.G. Pearse, Single cellular origin of somatostatin and calcitonin in the rat thyroid gland. Histochemistry 53(3), 243–247 (1977). https://doi.org/10.1007/bf00511079

    Article  PubMed  Google Scholar 

  59. B.R. Haugen, Drugs that suppress TSH or cause central hypothyroidism. Best practice & research. Clin. Endocrinol. Metab. 23(6), 793–800 (2009). https://doi.org/10.1016/j.beem.2009.08.003

    Article  CAS  Google Scholar 

  60. B.M. Lewis, C. Dieguez, M.D. Lewis, M.F. Scanlon, Dopamine stimulates release of thyrotrophin-releasing hormone from perfused intact rat hypothalamus via hypothalamic D2-receptors. J. Endocrinol. 115(3), 419–424 (1987). https://doi.org/10.1677/joe.0.1150419

    Article  CAS  PubMed  Google Scholar 

  61. D. Mannavola, L. Persani, G. Vannucchi, M. Zanardelli, L. Fugazzola, U. Verga, M. Facchetti, P. Beck-Peccoz, Different responses to chronic somatostatin analogues in patients with central hyperthyroidism. Clin. Endocrinol. 62(2), 176–181 (2005). https://doi.org/10.1111/j.1365-2265.2004.02192.x

    Article  CAS  Google Scholar 

  62. M.H. Samuels, P. Henry, E.C. Ridgway, Effects of dopamine and somatostatin on pulsatile pituitary glycoprotein secretion. J. Clin. Endocrinol. Metab. 74(1), 217–222 (1992). https://doi.org/10.1210/jcem.74.1.1345783

    Article  CAS  PubMed  Google Scholar 

  63. A. Gruszka, M.D. Culler, S. Melmed, Somatostatin analogs and chimeric somatostatin-dopamine molecules differentially regulate human growth hormone and prolactin gene expression and secretion in vitro. Mol. Cell. Endocrinol. 362(1-2), 104–109 (2012). https://doi.org/10.1016/j.mce.2012.05.020

    Article  CAS  PubMed  Google Scholar 

  64. M. Boscaro, W.H. Ludlam, B. Atkinson, J.E. Glusman, S. Petersenn, M. Reincke, P. Snyder, A. Tabarin, B.M. Biller, J. Findling, S. Melmed, C.H. Darby, K. Hu, Y. Wang, P.U. Freda, A.B. Grossman, L.A. Frohman, J. Bertherat, Treatment of pituitary-dependent Cushing’s disease with the multireceptor ligand somatostatin analog pasireotide (SOM230): a multicenter, phase II trial. J. Clin. Endocrinol. Metab. 94(1), 115–122 (2009). https://doi.org/10.1210/jc.2008-1008

    Article  CAS  PubMed  Google Scholar 

  65. A. Ben-Shlomo, S. Melmed, Somatostatin agonists for treatment of acromegaly. Mol. Cell. Endocrinol. 286(1–2), 192–198 (2008). https://doi.org/10.1016/j.mce.2007.11.024

    Article  CAS  PubMed  Google Scholar 

  66. J. Yang, N. Yi, J. Zhang, W. He, D. He, W. Wu, S. Xu, F. Li, G. Fan, X. Zhu, Z. Xue, W. Zhou, Generation and characterization of a hypothyroidism rat model with truncated thyroid stimulating hormone receptor. Sci. Rep. 8(1), 4004 (2018). https://doi.org/10.1038/s41598-018-22405-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by grants from the CIHR (MOP 74465) and NSERC (402594-11) to U.K. S.S. was supported by a fellowship from Shastri Indo-Canadian Institute (SICI), India. Special thanks to Glenmark Pharmaceutical India, for providing rats for the study. PTU and LVT were kind gifts from Panchsheel Organics Ltd., Mumbai, India and Macleods Pharmaceuticals Ltd., Mumbai, India respectively. We also thank Dr Sudhamani for preparing paraffin-embedded thyroid tissue blocks.

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Rat experimental model of hypothyroid was made by S.S. and V.P. at Principal K. M. Kundnani college of Pharmacy, Mumbai. All paraffin blocks were sectioned and processed for H&E staining commercially at Wax-it Histology Services, Inc, Vancouver. Immunohistochemistry presented in this manuscript was performed at The University of British Columbia, Vancouver by S.S. and R.K.S. The manuscript was written by S.S. and R.K.S. and edited by V.P. and U.K.

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Correspondence to Ujendra Kumar.

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This article does not contain any studies with human participants. All animals-related experiments were conducted according to the guidelines approved and reviewed by the Institutional Animal Ethics Committee (Animal House Registration no. 25/PO/ReBi/S/99/CPCSEA).

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Singh, S., Somvanshi, R.K., Panda, V. et al. Comparative distribution of somatostatin and somatostatin receptors in PTU-induced hypothyroidism. Endocrine 70, 92–106 (2020). https://doi.org/10.1007/s12020-020-02309-1

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  • DOI: https://doi.org/10.1007/s12020-020-02309-1

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