Journal of Clinical Endocrinology & Metabolism, Vol 80, 3621-3627, Copyright © 1995 by Endocrine Society

ARTICLES

Cell-specific expression of estrogen receptor in the human pituitary and its adenomas

M Zafar, S Ezzat, L Ramyar, N Pan, HS Smyth and SL Asa
Department of Pathology, Mount Sinai Hospital, Toronto, Ontario, Canada.

Estrogen affects the synthesis and release of several pituitary hormones. The estrogen receptor (ER), a member of the steroid hormone receptor family, is thought to mediate transcriptional effects in a cell-specific fashion. We investigated whether ER is expressed in specific hormone-producing cell types in the human pituitary and its adenomas. Pituitary adenomas (n = 34) were collected at the time of surgery, and normal glands were obtained from autopsy. Expression of ER messenger ribonucleic acid (mRNA) was determined by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. ER was also localized with immunohistochemistry and protein extraction. By RT-PCR, ER mRNA was found in the nontumorous pituitary and in pituitary adenomas expressing only PRL, in those producing GH and PRL, and in adenomas expressing the gonadotropic hormones. No ER mRNA was detected in adenomas expressing only GH without PRL or gonadotropins, nor in tumors producing ACTH without PRL or gonadotropins. In situ hybridization was not as sensitive or specific as RT-PCR. Biochemical analysis performed on seven tumors that were positive for ER mRNA by RT-PCR detected ER protein in only one PRL adenoma and one oncocytoma and yielded negative or equivocal results in one PRL adenoma, three GH-PRL adenomas, and one null cell adenoma. ER protein was localized by immunohistochemistry in scattered cells of the nontumorous adenohypophysis and in a few PRL and gonadotroph adenomas. We conclude that ER expression, as determined by RT-PCR, correlates with the expression of PRL or gonadotropins; in contrast, ER mRNA was not detected in adenomas that express only GH or ACTH. These findings implicate ER as a cell-specific transcription factor that may regulate cytodifferentiation in the pituitary.

This article has been cited by other articles:

				M. Cosma, J. Bailey, J. M. Miles, C. Y. Bowers, and J. D. Veldhuis Pituitary and/or Peripheral Estrogen-Receptor {alpha} Regulates Follicle-Stimulating Hormone Secretion, Whereas Central Estrogenic Pathways Direct Growth Hormone and Prolactin Secretion in Postmenopausal Women J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 951 - 958. [Abstract] [Full Text] [PDF]

				N. Ben-Jonathan, C. R. LaPensee, and E. W. LaPensee What Can We Learn from Rodents about Prolactin in Humans? Endocr. Rev., February 1, 2008; 29(1): 1 - 41. [Abstract] [Full Text] [PDF]

				N Y Y Al-Brahim and S L Asa My approach to pathology of the pituitary gland J. Clin. Pathol., December 1, 2006; 59(12): 1245 - 1253. [Abstract] [Full Text] [PDF]

				D. Giacomini, M. Paez-Pereda, M. Theodoropoulou, M. Labeur, D. Refojo, J. Gerez, A. Chervin, S. Berner, M. Losa, M. Buchfelder, et al. Bone Morphogenetic Protein-4 Inhibits Corticotroph Tumor Cells: Involvement in the Retinoic Acid Inhibitory Action Endocrinology, January 1, 2006; 147(1): 247 - 256. [Abstract] [Full Text] [PDF]

				D. G. Morris, B. Kola, N. Borboli, G. A. Kaltsas, M. Gueorguiev, A. M. McNicol, R. Ferrier, T. H. Jones, S. Baldeweg, M. Powell, et al. Identification of Adrenocorticotropin Receptor Messenger Ribonucleic Acid in the Human Pituitary and Its Loss of Expression in Pituitary Adenomas J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 6080 - 6087. [Abstract] [Full Text] [PDF]

				D. A. Schreihofer, D. F. Rowe, E. F. Rissman, E. M. Scordalakes, J.-a. Gustafsson, and M. A. Shupnik Estrogen Receptor-{alpha} (ER{alpha}), But Not ER{beta}, Modulates Estrogen Stimulation of the ER{alpha}-Truncated Variant, TERP-1 Endocrinology, November 1, 2002; 143(11): 4196 - 4202. [Abstract] [Full Text] [PDF]

				S. J. B. Aylwin, J. P. Welch, C. L. Davey, J. F. Geddes, D. F. Wood, G. M. Besser, A. B. Grossman, J. P. Monson, and J. M. Burrin The Relationship between Steroidogenic Factor 1 and DAX-1 Expression and in Vitro Gonadotropin Secretion in Human Pituitary Adenomas J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2476 - 2483. [Abstract] [Full Text] [PDF]

				U. Pagotto, T. Arzberger, M. Theodoropoulou, Y. Grübler, C. Pantaloni, W. Saeger, M. Losa, L. Journot, G. K. Stalla, and D. Spengler The Expression of the Antiproliferative Gene ZAC Is Lost or Highly Reduced in Nonfunctioning Pituitary Adenomas Cancer Res., December 1, 2000; 60(24): 6794 - 6799. [Abstract] [Full Text]

				E. Nishihara, Y. Nagayama, S. Inoue, H. Hiroi, M. Muramatsu, S. Yamashita, and T. Koji Ontogenetic Changes in the Expression of Estrogen Receptor {alpha} and {beta} in Rat Pituitary Gland Detected by Immunohistochemistry Endocrinology, February 1, 2000; 141(2): 615 - 620. [Abstract] [Full Text] [PDF]

				V. L. Green, V. Speirs, A. M. Landolt, P. M. Foy, and S. L. Atkin 17{beta}-Hydroxysteroid Dehydrogenase Type 1, 2, 3, and 4 Expression and Enzyme Activity in Human Anterior Pituitary Adenomas J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1340 - 1345. [Abstract] [Full Text]

				S. L. Asa and S. Ezzat The Cytogenesis and Pathogenesis of Pituitary Adenomas Endocr. Rev., December 1, 1998; 19(6): 798 - 827. [Abstract] [Full Text]

				M. A. Shupnik, L. K. Pitt, A. Y. Soh, A. Anderson, M. B. Lopes, and E. R. Laws Jr. Selective Expression of Estrogen Receptor {alpha} and {beta} Isoforms in Human Pituitary Tumors J. Clin. Endocrinol. Metab., November 1, 1998; 83(11): 3965 - 3972. [Abstract] [Full Text]

				S. L. Asa, K. Somers, and S. Ezzat The MEN-1 Gene Is Rarely Down-Regulated in Pituitary Adenomas J. Clin. Endocrinol. Metab., September 1, 1998; 83(9): 3210 - 3212. [Abstract] [Full Text]

				S. S. Chaidarun, B. Swearingen, and J. M. Alexander Differential Expression of Estrogen Receptor-{beta} (ER{beta}) in Human Pituitary Tumors: Functional Interactions with ER{alpha} and a Tumor-Specific Splice Variant J. Clin. Endocrinol. Metab., September 1, 1998; 83(9): 3308 - 3315. [Abstract] [Full Text]

				S. S. Chaidarun, A. Klibanski, and J. M. Alexander Tumor-Specific Expression of Alternatively Spliced Estrogen Receptor Messenger Ribonucleic Acid Variants in Human Pituitary Adenomas J. Clin. Endocrinol. Metab., April 1, 1997; 82(4): 1058 - 1065. [Abstract] [Full Text] [PDF]

				S. A. A. Abbass, S. L. Asa, and S. Ezzat Altered Expression of Fibroblast Growth Factor Receptors in Human Pituitary Adenomas J. Clin. Endocrinol. Metab., April 1, 1997; 82(4): 1160 - 1166. [Abstract] [Full Text] [PDF]