Sıçanların Lakrimal Bezlerinde Östrojen ve Progesteron Reseptörlerinin İmmunohistokimyasal Ekspresyonu

Abstract

Seks steroid hormonları (östrojen ve progesteron) spesifik reseptörleri aracılığıyla lakrimal bez fonksiyonlarının önemli düzenleyicisidirler. Bu hormonların eksikliği göz kuruluğu ile karakterize keratokonjuktivitis sikka (KCS) hastalığına neden olmaktadır. Sunulan çalışma, erişkin erkek sıçanların intraorbital ve ekstraorbital lakrimal bezinde östrojen reseptör α (ERα), östrojen reseptör β (ERβ) ve progesteron reseptörlerinin (PR) immunohistokimyasal lokalizasyonlarını ortaya koymak amacıyla planlandı. Anastezi altında 8 adet erkek sıçandan elde edilen lakrimal doku örneklerine rutin histolojik prosedürü takiben Strep-ABC immunohistokimyasal boyama tekniği uygulandı. İntraorbital ve ekstraorbital bez epiteli, akıtıcı kanal epiteli, miyoepitel ve kan damarların endotel hücrelerinin hem sitoplazmasında hem de çekirdeğinde değişen derecelerde ERα, ERβ ve PR immunreaktivitesi saptandı. Her iki bezin bütün yapısal komponentlerinde ERα en yoğun olarak çekirdekte bulunurken, ERβ’nın en yoğun sitoplazmada lokalize olduğu tespit edildi. PR immunreaktivitesinin ise hem intraorbital hem de ekstraorbital bez epitelinin lateral membranlarında ve intraorbital bezin miyoepitel hücrelerinde kuvvetli olduğu gözlendi. Aynı zamanda intraorbital bezlerde kan damarlarının etrafında bulunan mast hücrelerinde pozitif ERβ immunreaksiyonu saptanırken, ekstraorbital bezin intersitisyel bağ dokusu içinde ERα, ERβ ve PR pozitif stromal hücrelere rastlandı. Sonuç olarak, erkek sıçanlarda intraorbital ve ekstraorbital bezin bütün yapısal komponentlerinde değişen derecelerde ERα, ERβ ve PR immunreaktivitesinin saptanması lakrimal bezin yapısal ve fonksiyonel bütünlüğünü sürdürmede östrojen ve progesteron hormonlarının reseptör bazlı etkisinin olduğu fikrini desteklemektedir.

Keywords

• Östrojen Reseptör,Lakrimal Bez,Progesteron Reseptör,Sıçan

Immunohistochemical Expression of Estrogen and Progesterone Receptors in the Lacrimal Glands of the Rats

Abstract

Sex steroid hormones (estrogen and progesterone) are important regulators in lacrimal gland functions with the help of its specific receptors. The deficiency of these hormones causes disease of keratoconjunctivitis sicca (KCS) which is characterized with eye dryness. This study was aimed to show the immunohistochemical localization of the ERα, ERβ and PR in intraorbital and extraorbital lacrimal glands of the rat. Following the routine histological procedure, the Strep-ABC immunohistochemical staining method was performed to the lacrimal gland samples obtained from 8 rats under anesthesia. Changing degrees of ERα, ERβ and PR immunoreactivity were determined in cytoplasm and nucleus of the secretory epithelium, duct epithelium, myoepithelial cells and endothelial cells of the intraorbital and extraorbital gland. It was determined that ERα was found intensely in the nucleus of the all structural components of the two glands, whereas ERβ was found intensely located in the cytoplasm. PR immunoreactivity was shown strongly in the lateral membranes of both gland epithelium and in the myoepithelial cells of the intraorbital glands. Also, positive ERβ immunoreaction was detected in the mast cells around the blood vessels in the intraorbital glands, whereas ERα, ERβ and PR positive stromal cells were detected in the interstitial connective tissue of the extraorbital gland. As a conclusion, changing degrees of ERα, ERβ and PR immunoreactivity found in all structural components of both glands supports the idea that the receptor based estrogen and progesterone hormones have an effect on the maintainance of the structural and functional integrity of the lacrimal gland.

Keywords

• Estrogen Receptor,Lacrimal Gland,Progesterone Receptor,Rat

References

1. Abdo FK, EL-Gammal AA, Abdel Fattah EA, Abdel-Haleim MR. The role of hormone replacement therapy on structural integrity of lacrimal gland in ovariectomized albino rats (histological and immunohistochemical study). Egypt J Histol. 2009; 32: 66-80.
2. Azzarolo AM, Eihausen H, Schechter J. Estrogen prevention of lacrimal gland cell death and lymphocytic infiltration. Exp Eye Res. 2003; 77: 347-354.
3. Brann DW, Hendry LB, Mahesh VB. Emerging diversities in the mechanism of action of steroid hormones. J Steroid Biochem Mol Biol. 1995; 52: 113-133.
4. Brown NM, Lamartiniere CA. Genistein regulation of transforming growth factor-a, epidermal growth factor (EGF), and EGF Receptor expression in the rat uterus and vagina. Cell Growth Differ. 2000; 11: 255-260.
5. Camacho-Arroyo I, Cerbón MA, Gamboa-Domínguez A, González-Agüero G, González-Mariscal G. Immunohistochemical detection of estrogen and progesterone receptors in the rabbit submandibular gland. Comp Biochem Physiol A. 1999; 123: 179-186.
6. Cooke PS, Buchanan DL, Lubahn DB, Cunha GR. Mechanism of estrogen action: Lessons fron the estrogen receptor-alpha knockout mouse. Biol Reprod. 1998; 59: 470-475.
7. Esmaeli B, Harvey JT, Hewlett B. Immunohistochemical evidence for estrogen receptors in meibomian glands. Ophthalmology 2000; 107: 180-184.
8. Fuchsjäger-Mayrl G, Nepp J, Schneeberger C, Sator M, Dietrich W, Wedrich A, Huber J, Tschugguel W. Identification of estrogen and progesterone receptor mRNA expression in the conjunctiva of premenopausel woman. Invest Ophthalmol Vis Sci. 2002; 43: 2841-2844.

9. Gans LA, Lee SF, Lemp MA, Pepose JS. Estrogen and progesterone receptors and human conjunctiva. Am J Ophthalmol. 1990; 109: 474-477.
10. Gligorijević J, Krstić M, Babić G. Imnunohistochemical detection of estrogen and progesterone receptors in the human lacrimal gland. Arch Biol Sci Belgrade. 2011; 63: 319-324.
11. Gupta PD, Johar K Sr, Nagpal K, Vasavada AR. Sex hormone receptors in the human eye. Surv Ophthalmol 2005; 50: 274-284.
12. Hadeyama T, Nakayasu K, Ha NT, Nakamura S. Expression of estrogen receptors alpha and beta, androgen receptors and progesterone receptors in human cornea. Nippon Ganka Gakkai Zasshi. 2002; 106: 557-564.
13. Heldring N, Pike A, Andersson S, Matthews J, Cheng G, Hartman J, Tujague M, Strom A, Treuter E, Warner M, Gustafsson JA. Estrogen receptors: how do they signal and what are their targets. Physiol Rev. 2007; 87: 905-931.
14. Herynk MH, Fuqua SA. Estrogen receptor mutations in human disease. Endocr Rev. 2004; 25: 869-898.
15. Hewitt SC, Deroo BJ, Korach KS. Signal transduction: a new mediator for an old hormone? Science 2005; 307: 1572-1573.
16. Huang ZM, Azzarolo AM, Mircheff AK, Esrail R, Grayson G, Heller K, et al. Does estrogen directly affect lacrimal gland function? ARVO Abstract, Invest Ophthalmol Vis Sci. 1995; 36: S2979
17. Iwamoto T, Jakobiec FA. Lacrimal glands. In: Duane TD, Jaeger EA, eds. Biomedical foundation of ophthalmology. Vol 1. Revised ed. Philadelphia, Harper & Row, 1985; 30, 1.
18. Krawczuk-Hermanowiczowa O. Effects of sexual glands on the lacrimal gland. II. Changes in rat lacrimal galnds after castration. Klin Oczna 1983; 85: 15-17.
19. Lauria A, Porcelli F. Leucine aminopeptidase (LAP) activity and sexual dimorphism in rat exorbital gland. Basic Appl Histochem 1979; 23: 171-177.
20. Luetjens CM, Didolkar A, Kliesch S, Paulus W, Jeibmann A, Böcker W, Nieschlag E, Simoni M. Tissue expression of the nuclear progesterone receptor in male non-human primates and men. J Endocrinol. 2006; 189: 529-539.
21. Munaut C, Lambert V, Noël A, Frankenne F, Deprez M, Foidart JM, Rakic JM. Presence of oestrogen receptor type β in human retina. Br J Ophthalmol. 2001; 85: 877-882.
22. Ogueta SB, Schwartz SD, Yamashita CK, Farber DB. Estrogen receptor in the human eye: influence of gender and age on gene expression. Invest Ophthalmol Vis Sci. 1999; 40: 1906-1911.
23. Pavao M, Traish AM. Estrogen receptor antibodies: specificity and utility in detection, localization and analyses of estrogen receptor α and β. Review article. Steroids. 2001; 66: 1-16.
24. Ranganathan V, De PK. Androgens and estrogens markedly inhibit expression of a 20 kDa major protein in hamster exorbital lacrimal gland. Biochem Biophys Res Commun 1995; 208: 412-417.
25. Schaumberg DA, Buring JE, Sullivan DA, Dana MR. Hormone replacement therapy and dry eye syndrome. JAMA. 2001; 286: 2114-2119.
26. Singh S, Shaul PW, Gupta PD. Conventional estrogen receptors are found in the plasma membrane of vaginal epithelial cells oft he rat. Steroids. 2002; 67: 757-764.
27. Spelsberg H, Klueppel M, Reinhard T, Glaeser M, Niederacher D, Beckmann MW, Sundmacher R. Detection of Oestrogen receptors (ER) α and β in conjunctiva, lacrimal gland, and tarsal plates. Eye. 2004; 18: 729-733.
28. Stefano GB, Prevot V, Beauvillain JC, Cadet P, Fimiani C, Welters I, Fricchione GL, Breton C, Lassalle P, Salzet M, Bilfinger TV. Cell-surface estrogen receptors mediate calcium-dependent nitric oxide release in human endothelia. Circulation 2000; 101: 1594-1597.
29. Sullivan DA, Bloch KJ, Allansmith MR. Hormonal influence on the secretory immune system of the eye: androgen regulation of secretory component levels in rat tears. J Immunol. 1984; 132: 1130-1135.
30. Sullivan DA, Edwards JA, Wickham LA, Pena JD, Gao J, Ono M, Kelleher RS. Identification and endocrine control of sex steroid binding sites in the lacrimal gland. Curr Eye Res. 1996; 15: 279-291
31. Suzuki T, Kinoshita Y, Tachibana M, Matsushima Y, Kobayashi Y, Adachi W, Sotozono C, Kinoshita S. Expression of sex steroid hormone receptors in human cornea. Curr Eye Res. 2001; 22: 28-33.
32. Suzuki T, Schirra F, Richards SM, Trister NS, Lombardi MJ, Rowley P, Jensen RV, Sullivan DA. Estrogen’s and progesterone’s impact on gene expression in the mouse lacrimal gland. Invest Ophthalmol Vis Sci. 2006; 47: 158-168.
33. Tachibana M, Kasukabe T, Kobayashi Y, Suzuki T, Kinoshita S, matsushima Y. Expression of estrogen receptor alpha and beta in the mouse cornea. Invest Ophthalmol Vis Sci. 2000; 41: 668-670.
34. Tisinti M, Kassi E, Korkolopoulou P, Kapsogeorgou E, Moutsatsou P, Patsouris E, Manoussakis MN. Function estrogen receptors alpha and beta are expressed in normal human salivary gland epithelium and apparently mediate immunomodulatory effects. Eur J Oral Sci. 2009; 117: 498-505.
35. Tsai M-J, O’Malley BW. Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Ann Rev Biochem. 1994; 63: 451-486.
36. Valimaa H, Savolainen S, Soukka T, Silvoniemi P, Makela S, Kujari H, Gustafsson JA, Laine M. Estrogen receptor-beta is the predominant estrogen receptor subtype in human oral epithelium and salivary glands. J Endocrinol. 2004; 180: 55-62.
37. Vegeto E, Shanbaz MM, Wen DX, Golman ME, O’Malley BW, McDonnel DP. Human progesterone receptor A form is a cell and promoter specific repressor of human progesterone receptor B function. Mol Endocrinol. 1993; 7: 1244-1255.
38. Véscei PV, Kircher K, Kaminski S, Nagel G, Breitenecker G, Kohberger PD. Immunohistochemical detection of estrogen and progesterone receptor in human cornea. Maturitas. 2000; 36: 169-172.
39. Wickham LA, Gao J, Toda I, Rocha EM, Ono M, Sullivan DA. Identification of androgen, estrogen and progesterone receptor mRNAs in the eye. Acta Ophthalmol Scand. 2000; 78: 146-153.
40. Wickham LA, Rocha EM, Gao J, Krenzer KL, da Silveira LA, Toda I, Sullivan DA. Identification and hormonal control of sex steroid receptors in the eye. Adv Exp Med. 1998; 438: 95-100.
41. Yanagiya N, Akiba J, Kado M, Yoshida A, Kono T, Iwamoto J. Transient corneal edema induced by niric oxide synthase inhibition. Nitric Oxide. 1997; 1: 397-403.