Skip to main content
Erschienen in: Pituitary 3/2013

01.09.2013

Aromatase cytochrome P450 enzyme expression in prolactinomas and its relationship to tumor behavior

verfasst von: Hakan Akinci, Aysegul Kapucu, Kadriye Akgun Dar, Ozlem Celik, Banu Tutunculer, Gozde Sirin, Buge Oz, Nurperi Gazioglu, Haluk Ince, Süheyla Aliustaoglu, Pinar Kadioglu

Erschienen in: Pituitary | Ausgabe 3/2013

Einloggen, um Zugang zu erhalten

Abstract

The aim of the study was to evaluate the presence of aromatase cytochrome P450 enzyme (P450AROM) expression in normal pituitary tissues and tumor tissues of patients with prolactinoma and to examine the impact of the P450AROM expression on clinical outcome. Twenty-six consecutive human pituitary tissue samples were obtained from autopsies performed at the Institute of Forensic Medicine. Sixty-four patients who had an adenomectomy between 2000 and 2009 after prolactinoma diagnosis with histologically confirmed pituitary tumor tissues were retrospectively included in this study. The slices from the pituitary tissues were subjected to immunohistochemical staining for evaluation of P450AROM and estrogen receptor beta (ER beta) subunit. Immunohistochemistry results were compared according to age, gender, remission rate, resistance and invasion status of the patients. Higher than normal P450AROM expression was found in the pituitary tissues of the patients with prolactinoma (p < 0.001). P450AROM intensity had no relation to resistance or remission in patients with prolactinoma (p = 0.44, p = 0.45, respectively). The subgroup analysis showed that compared to males without invasive adenoma, males with invasive adenoma had higher P450AROM expression (p = 0.048). ER beta was found to have an impact on resistance (p = 0.049). This study shows that P450AROM expression is present in the pituitary tissues of patients with prolactinoma and that this presence could be important in development and tumor behavior of prolactinomas.
Literatur
1.
Zurück zum Zitat Freeman ME, Kanyicska B, Lerant A et al (2000) PRL: structure, function, and regulation of secretion. Physiol Rev 80(4):1523–1631PubMed Freeman ME, Kanyicska B, Lerant A et al (2000) PRL: structure, function, and regulation of secretion. Physiol Rev 80(4):1523–1631PubMed
2.
Zurück zum Zitat Mancini T, Casanueva FF, Giustina A (2008) Hyperprolactinemia and prolactinomas. Endocrinol Metab Clin North Am 37:67–99CrossRefPubMed Mancini T, Casanueva FF, Giustina A (2008) Hyperprolactinemia and prolactinomas. Endocrinol Metab Clin North Am 37:67–99CrossRefPubMed
3.
Zurück zum Zitat Sasano H, Takahashi K, Satoh F, Nagura H, Harada N (1998) Aromatase in the human central nervous system. Clin Endocrinol (Oxf) 48:325–329CrossRef Sasano H, Takahashi K, Satoh F, Nagura H, Harada N (1998) Aromatase in the human central nervous system. Clin Endocrinol (Oxf) 48:325–329CrossRef
4.
Zurück zum Zitat Kadioglu P, Oral G, Sayitoglu M, Erensoy N, Senel B, Gazioglu N, Sav A, Cetin G, Ozbek U (2008) Aromatase cytochrome P450 enzyme expression in human pituitary. Pituitary 11:29–35CrossRefPubMed Kadioglu P, Oral G, Sayitoglu M, Erensoy N, Senel B, Gazioglu N, Sav A, Cetin G, Ozbek U (2008) Aromatase cytochrome P450 enzyme expression in human pituitary. Pituitary 11:29–35CrossRefPubMed
5.
Zurück zum Zitat Xu RK, Wu XM, Di AK, Xu JN, Pang CS, Pang SF (2000) Pituitary prolactin-secreting tumor formation: recent developments. Biol Signals Recept 9:1–20CrossRefPubMed Xu RK, Wu XM, Di AK, Xu JN, Pang CS, Pang SF (2000) Pituitary prolactin-secreting tumor formation: recent developments. Biol Signals Recept 9:1–20CrossRefPubMed
6.
Zurück zum Zitat Spady TJ, Harvell DME, Snyder MC, Pennington KL, McComb RD, Shull JD (1998) Estrogen-induced tumorigenesis in the Copenhagen rat: disparate susceptibilities to development of prolactin-producing pituitary tumors and mammary carcinomas. Cancer Lett 124:95–103CrossRefPubMed Spady TJ, Harvell DME, Snyder MC, Pennington KL, McComb RD, Shull JD (1998) Estrogen-induced tumorigenesis in the Copenhagen rat: disparate susceptibilities to development of prolactin-producing pituitary tumors and mammary carcinomas. Cancer Lett 124:95–103CrossRefPubMed
7.
Zurück zum Zitat Gottesfeld Z, Liehr JG (1987) Chronic exposure to random restraint stress retards the development of estrogen-induced pituitary prolactinoma in rats. Neurosci Lett 80:44–48CrossRefPubMed Gottesfeld Z, Liehr JG (1987) Chronic exposure to random restraint stress retards the development of estrogen-induced pituitary prolactinoma in rats. Neurosci Lett 80:44–48CrossRefPubMed
8.
Zurück zum Zitat Carretero J, Burks DJ, Vazquez G, Rubio M, Hernandez H, Bodego P, Vazquez R (2002) Expression of aromatase P450 is increased in spontaneous prolactinomas of aged rats. Pituitary 5:5–10CrossRefPubMed Carretero J, Burks DJ, Vazquez G, Rubio M, Hernandez H, Bodego P, Vazquez R (2002) Expression of aromatase P450 is increased in spontaneous prolactinomas of aged rats. Pituitary 5:5–10CrossRefPubMed
9.
Zurück zum Zitat Asscheman H, Gooren LJ, Assies J, Smits JP, de Slegte R (1988) Prolactin levels and pituitary enlargement in hormone-treated male-to-female transsexuals. Clin Endocrinol (Oxf) 28(6):583–588 Asscheman H, Gooren LJ, Assies J, Smits JP, de Slegte R (1988) Prolactin levels and pituitary enlargement in hormone-treated male-to-female transsexuals. Clin Endocrinol (Oxf) 28(6):583–588
10.
Zurück zum Zitat Prager D, Braunstein GD (1995) Pituitary disorders during pregnancy. Endocrinol Metab Clin North Am 24:1–14PubMed Prager D, Braunstein GD (1995) Pituitary disorders during pregnancy. Endocrinol Metab Clin North Am 24:1–14PubMed
11.
Zurück zum Zitat Garcia MM, Kapcala LP (1995) Growth of a microprolactinoma to a macroprolactinoma during estrogen therapy. J Endocrinol Invest 18(6):450–455PubMed Garcia MM, Kapcala LP (1995) Growth of a microprolactinoma to a macroprolactinoma during estrogen therapy. J Endocrinol Invest 18(6):450–455PubMed
12.
Zurück zum Zitat Prior JC, Cox TA, Fairholm D, Kosthashuk E, Nugent R (1987) Testosterone-related exacerbation of a prolactin-producing macroadenoma: possible role for estrogen. J Clin Endocrinol Metab 64:391–394CrossRefPubMed Prior JC, Cox TA, Fairholm D, Kosthashuk E, Nugent R (1987) Testosterone-related exacerbation of a prolactin-producing macroadenoma: possible role for estrogen. J Clin Endocrinol Metab 64:391–394CrossRefPubMed
13.
Zurück zum Zitat Gillam MP, Middler S, Freed DJ, Molitch M (2002) The novel use of very high doses of cabergoline and a combination of testosterone and an aromatase inhibitor in the treatment of a giant prolactinoma. J Clin Endocrinol Metab 87:4447–4451CrossRefPubMed Gillam MP, Middler S, Freed DJ, Molitch M (2002) The novel use of very high doses of cabergoline and a combination of testosterone and an aromatase inhibitor in the treatment of a giant prolactinoma. J Clin Endocrinol Metab 87:4447–4451CrossRefPubMed
14.
Zurück zum Zitat Sodi R, Fikri R, Diver M, Ranganath L, Vora J (2005) Testosterone replacement-induced hyperprolactinaemia: case report and review of the literature. Ann Clin Biochem 42:153–159CrossRefPubMed Sodi R, Fikri R, Diver M, Ranganath L, Vora J (2005) Testosterone replacement-induced hyperprolactinaemia: case report and review of the literature. Ann Clin Biochem 42:153–159CrossRefPubMed
15.
Zurück zum Zitat Heidari Z, Hosseinpanah F, Shirazian N (2010) Achievement of fertility in an infertile man with resistant macroprolactinoma using high-dose bromocriptine and a combination of human chorionic gonadotropin and an aromatase inhibitor. Endocr Pract 16:669–672CrossRefPubMed Heidari Z, Hosseinpanah F, Shirazian N (2010) Achievement of fertility in an infertile man with resistant macroprolactinoma using high-dose bromocriptine and a combination of human chorionic gonadotropin and an aromatase inhibitor. Endocr Pract 16:669–672CrossRefPubMed
16.
Zurück zum Zitat Lv H, Li C, Gui S, Zhang Y (2011) Expression of estrogen receptor α and growth factors in human prolactinoma and its correlation with clinical features and gender. J Endocrinol Invest. PMID 21422801 (epub ahead of print) Lv H, Li C, Gui S, Zhang Y (2011) Expression of estrogen receptor α and growth factors in human prolactinoma and its correlation with clinical features and gender. J Endocrinol Invest. PMID 21422801 (epub ahead of print)
17.
Zurück zum Zitat Gurlek A, Karavitaki N, Ansorge O, Wass JA (2007) What are the markers of aggressiveness in prolactinomas? Changes in cell biology, extracellular matrix components, angiogenesis and genetics. Eur J Endocrinol 156:143–153CrossRefPubMed Gurlek A, Karavitaki N, Ansorge O, Wass JA (2007) What are the markers of aggressiveness in prolactinomas? Changes in cell biology, extracellular matrix components, angiogenesis and genetics. Eur J Endocrinol 156:143–153CrossRefPubMed
18.
Zurück zum Zitat Detre S, Saccani Jotti G, Dowsett M (1995) A “quickscore” method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol 48:876–878CrossRefPubMed Detre S, Saccani Jotti G, Dowsett M (1995) A “quickscore” method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol 48:876–878CrossRefPubMed
19.
Zurück zum Zitat Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, Wass JA (2011) Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96(2):273–288CrossRefPubMed Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, Wass JA (2011) Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96(2):273–288CrossRefPubMed
20.
Zurück zum Zitat Kaltsas GA, Nomikos P, Kontogeorgos G, Buchfelder M, Grossman AB (2005) Clinical review: diagnosis and management of pituitary carcinomas. J Clin Endocrinol Metab 90(5):3089–3099CrossRefPubMed Kaltsas GA, Nomikos P, Kontogeorgos G, Buchfelder M, Grossman AB (2005) Clinical review: diagnosis and management of pituitary carcinomas. J Clin Endocrinol Metab 90(5):3089–3099CrossRefPubMed
21.
Zurück zum Zitat Fideleff HL, Boquete HR, Suarez MG, Azaretzky M (2009) Prolactinoma in children and adolescent. Horm Res 72:197–205CrossRefPubMed Fideleff HL, Boquete HR, Suarez MG, Azaretzky M (2009) Prolactinoma in children and adolescent. Horm Res 72:197–205CrossRefPubMed
22.
Zurück zum Zitat Thapar K, Kovacs K, Scheithauer BW, Stefaneanu L, Horvath E, Pernicone PJ, Murray D, Laws ER (1996) Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery 38:99–106CrossRefPubMed Thapar K, Kovacs K, Scheithauer BW, Stefaneanu L, Horvath E, Pernicone PJ, Murray D, Laws ER (1996) Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery 38:99–106CrossRefPubMed
23.
Zurück zum Zitat Ma W, Ikeda H, Yoshimoto T (2002) Clinicopathologic study of 123 cases of prolactin-secreting pituitary adenomas with special reference to multihormone production and clonality of the adenomas. Cancer 95:258–266CrossRefPubMed Ma W, Ikeda H, Yoshimoto T (2002) Clinicopathologic study of 123 cases of prolactin-secreting pituitary adenomas with special reference to multihormone production and clonality of the adenomas. Cancer 95:258–266CrossRefPubMed
24.
Zurück zum Zitat Scheithauer BW, Gaffey TA, Lloyd RV, Sebo TJ, Kovacs KT, Horvath E, Yapicier O, Young WF, Meyer FB, Kuroki T, Riehle DL, Laws ER (2006) Pathobiology of pituitary adenomas and carcinomas. Neurosurgery 59:341CrossRefPubMed Scheithauer BW, Gaffey TA, Lloyd RV, Sebo TJ, Kovacs KT, Horvath E, Yapicier O, Young WF, Meyer FB, Kuroki T, Riehle DL, Laws ER (2006) Pathobiology of pituitary adenomas and carcinomas. Neurosurgery 59:341CrossRefPubMed
25.
Zurück zum Zitat Wu ZB, Zheng WM, Su ZP, Chen Y, Wu JS, Wang CD, Lin C, Zeng YJ, Zhuge QC (2010) Expression of D2RmRNA isoforms and ERmRNA isoforms in prolactinomas: correlation with the response to bromocriptine and with tumor biological behavior. J Neurooncol 99(1):25–32CrossRefPubMed Wu ZB, Zheng WM, Su ZP, Chen Y, Wu JS, Wang CD, Lin C, Zeng YJ, Zhuge QC (2010) Expression of D2RmRNA isoforms and ERmRNA isoforms in prolactinomas: correlation with the response to bromocriptine and with tumor biological behavior. J Neurooncol 99(1):25–32CrossRefPubMed
26.
Zurück zum Zitat Passos VQ, Fortes MA, Giannella-Neto D, Bronstein MD (2009) Genes differentially expressed in prolactinomas responsive and resistant to dopamine agonists. Neuroendocrinology 89(2):163–170CrossRefPubMed Passos VQ, Fortes MA, Giannella-Neto D, Bronstein MD (2009) Genes differentially expressed in prolactinomas responsive and resistant to dopamine agonists. Neuroendocrinology 89(2):163–170CrossRefPubMed
27.
Zurück zum Zitat Cristina C, Diaz-Torga GS, Goya RG, Kakar SS, Perez-Millan MI, Passos VQ, Giannella-Neto D, Bronstein MD, Becu-Villalobos D (2007) PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes. Mol Cancer 6:4CrossRefPubMed Cristina C, Diaz-Torga GS, Goya RG, Kakar SS, Perez-Millan MI, Passos VQ, Giannella-Neto D, Bronstein MD, Becu-Villalobos D (2007) PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes. Mol Cancer 6:4CrossRefPubMed
28.
Zurück zum Zitat Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD, Melmed S (1999) Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab 84(2):761–767CrossRefPubMed Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD, Melmed S (1999) Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab 84(2):761–767CrossRefPubMed
29.
Zurück zum Zitat Burdman JA, Pauni M, Heredia Sereno GM, Bordón AE (2008) Estrogen receptors in human pituitary tumors. Horm Metab Res 40(8):524–527CrossRefPubMed Burdman JA, Pauni M, Heredia Sereno GM, Bordón AE (2008) Estrogen receptors in human pituitary tumors. Horm Metab Res 40(8):524–527CrossRefPubMed
30.
Zurück zum Zitat Kaptain GJ, Simmons NE, Alden TD, Lopes MB, Vance ML, Laws ER (1999) Estrogen receptors in prolactinomas: a clinico-pathological study. Pituitary 1:91–98CrossRefPubMed Kaptain GJ, Simmons NE, Alden TD, Lopes MB, Vance ML, Laws ER (1999) Estrogen receptors in prolactinomas: a clinico-pathological study. Pituitary 1:91–98CrossRefPubMed
31.
Zurück zum Zitat Zafar M, Ezzai S, Raymyar L, Pan N, Smyth HS, Asa SL (1995) Cell-specific expression of estrogen receptor in the human pituitary and its adenomas. J Clin Endocrinol Metab 80:3621–3627CrossRefPubMed Zafar M, Ezzai S, Raymyar L, Pan N, Smyth HS, Asa SL (1995) Cell-specific expression of estrogen receptor in the human pituitary and its adenomas. J Clin Endocrinol Metab 80:3621–3627CrossRefPubMed
Metadaten
Titel
Aromatase cytochrome P450 enzyme expression in prolactinomas and its relationship to tumor behavior
verfasst von
Hakan Akinci
Aysegul Kapucu
Kadriye Akgun Dar
Ozlem Celik
Banu Tutunculer
Gozde Sirin
Buge Oz
Nurperi Gazioglu
Haluk Ince
Süheyla Aliustaoglu
Pinar Kadioglu
Publikationsdatum
01.09.2013
Verlag
Springer US
Erschienen in
Pituitary / Ausgabe 3/2013
Print ISSN: 1386-341X
Elektronische ISSN: 1573-7403
DOI
https://doi.org/10.1007/s11102-012-0436-2

Weitere Artikel der Ausgabe 3/2013

Pituitary 3/2013 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

29.05.2024 Herzinfarkt Nachrichten

Bei Menschen mit Typ-2-Diabetes sind die Chancen, einen Myokardinfarkt zu überleben, in den letzten 15 Jahren deutlich gestiegen – nicht jedoch bei Betroffenen mit Typ 1.

15% bedauern gewählte Blasenkrebs-Therapie

29.05.2024 Urothelkarzinom Nachrichten

Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.

Costims – das nächste heiße Ding in der Krebstherapie?

28.05.2024 Onkologische Immuntherapie Nachrichten

„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.