Involvement of activin/BMP system in development of human pituitary gonadotropinomas and nonfunctioning adenomas.
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.
Takeda
Masaya
M
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama City 700-8558, Japan.
Otsuka
Fumio
F
Suzuki
Jiro
J
Kishida
Masayuki
M
Ogura
Toshio
T
Tamiya
Takashi
T
Makino
Hirofumi
H
D028341:Activins / Q000378:metabolism*; D000236:Adenoma / Q000378:metabolism; D000328:Adult; D000368:Aged; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002455:Cell Division; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism; D038681:Follistatin / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006801:Humans; D008024:Ligands; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010911:Pituitary Neoplasms / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D019485:Bone Morphogenetic Proteins; D038681:Follistatin; D008024:Ligands; D012333:RNA, Messenger; D028341:Activins; D007987:Gonadotropin-Releasing Hormone; D012313:RNA; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone