G-protein Coupled Estrogen Receptor Expression in Growth Hormone Secreting and Non-Functioning Adenomas

Hande Mefkure Ozkaya; Muge Sayitoglu; Nil Comunoglu; Eda Sun; Fatma Ela Keskin; Duygu Ozata; Rabia Hacer Hocaoglu; Khusan Khodzaev; Sinem Firtina; Necmettin Tanriover; Nurperi Gazioglu; Buge Oz; Pinar Kadioglu

doi:10.1055/a-1274-1330

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2021; 129(09): 634-643
DOI: 10.1055/a-1274-1330

Article

G-protein Coupled Estrogen Receptor Expression in Growth Hormone Secreting and Non-Functioning Adenomas

Authors

Hande Mefkure Ozkaya

¹Department of Endocrinology and Metabolism, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul
Muge Sayitoglu

²Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul
Nil Comunoglu

³Department of Pathology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul
Eda Sun

²Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul
Fatma Ela Keskin

⁴Department of Endocrinology and Metabolism, Demiroglu Bilim University, Istanbul
Duygu Ozata

⁵Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul
Rabia Hacer Hocaoglu

⁵Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul
Khusan Khodzaev

²Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul
Sinem Firtina

²Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul
Necmettin Tanriover

⁶Department of Neurosurgery, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul

⁸Pituitary Center, Istanbul University-Cerrahpasa, Istanbul
Nurperi Gazioglu

⁷Department of Neurosurgery, Demiroglu Bilim University, Istanbul
Buge Oz

³Department of Pathology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul
Pinar Kadioglu

¹Department of Endocrinology and Metabolism, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul

⁸Pituitary Center, Istanbul University-Cerrahpasa, Istanbul

Abstract

Purpose To evaluate the expression of G-protein coupled estrogen receptor (GPER1), aromatase, estrogen receptor α (ERα), estrogen receptor β (ERβ), pituitary tumor transforming gene (PTTG), and fibroblast growth factor 2 (FGF2) in GH-secreting and non-functioning adenomas (NFA).

Methods Thirty patients with acromegaly and 27 patients with NFA were included. Gene expression was determined via quantitative reverse transcription polymerase chain reaction (QRT-PCR). Protein expression was determined via immunohistochemistry.

Results There was no difference, in terms of gene expression of aromatase, ERα, PTTG, and FGF2 between the two groups (p>0.05 for all). ERβ gene expression was higher and GPER1 gene expression was lower in GH-secreting adenomas than NFAs (p<0.05 for all). Aromatase and ERβ protein expression was higher in GH-secreting adenomas than NFAs (p=0.01). None of the tumors expressed ERα. GPER1 expression was detected in 62.2% of the GH-secreting adenomas and 45% of NFAs. There was no difference in terms of GPER1, PTTG, FGF2 H scores between the two groups (p>0.05 for all). GPER1 gene expression was positively correlated to ERα, ERβ, PTTG, and FGF2 gene expression (p<0.05 for all). There was a positive correlation between aromatase and GPER1 protein expression (r=0.31; p=0.04).

Conclusions GPER1 is expressed at both gene and protein level in a substantial portion of GH-secreting adenomas and NFAs. The finding of a positive correlation between GPER1 and ERα, ERβ, PTTG, and FGF2 gene expression and aromatase and GPER1 protein expression suggests GPER1 along with aromatase and classical ERs might mediate the effects of estrogen through upregulation of PTTG and FGF2.

Key words

acromegaly - aromatase - estrogens - hormones - GPER1 - pituitary tumor

Full Text

References

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