Involvement of activin/BMP system in development of human pituitary gonadotropinomas and nonfunctioning adenomas |
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Authors: | Takeda Masaya Otsuka Fumio Suzuki Jiro Kishida Masayuki Ogura Toshio Tamiya Takashi Makino Hirofumi |
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Institution: | Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama City 700-8558, Japan. |
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Abstract: | Roles of activin/bone morphogenetic protein (BMP) system in the pathogenesis of human pituitary adenoma remain unknown although these factors stimulate follicle-stimulating hormone (FSH) secretion in the normal pituitary. Here we demonstrated that type-I and -II subunit mRNAs of activin/BMP receptors are expressed in Pit-1-negative FSH-producing (FSH-oma) and nonfunctioning pituitary adenomas (NF-oma). Basal levels of serum FSH standardized by luteinizing hormone (LH) were markedly high in FSH-omas in contrast to NF-omas. However, gonadotropin-releasing hormone (GnRH)-induced increment of FSH standardized by that of LH was not changed in FSH-omas, suggesting that imbalanced FSH secretion by FSH-oma is not attributable to GnRH regardless of the expression of GnRH receptor. Although activin betaA subunit was detected in neither adenoma, the betaB subunit was expressed highly in FSH-omas and, to lesser extent, in NF-omas. As for BMPs, BMP-6 and -7 were detected in NF-omas while BMP-4 and -15 were not detected in either type of adenoma. In the presence of pituitary activin/BMP system, the levels of co-expressing follistatin mRNA in the tumors were reduced in FSH-oma compared with NF-oma, suggesting that endogenous follistatin is involved in FSH overproduction through inhibition of activin/BMP system independently of GnRH. |
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Keywords: | Activin Bone morphogenetic protein Follicle-stimulating hormone Follistatin Gonadotropinoma Gonadotropin-releasing hormone Luteinizing hormone Macroadenoma Pituitary adenoma |
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