Induction of GH, PRL, and TSH beta mRNA by transfection of Pit-1 in a human pituitary adenoma-derived cell line.
The functional development of pituitary cells depends on the expression of a combination of transcription factors and co-factors. Pituitary-specific transcription factor-1 (Pit-1) is required for the expression of growth hormone (GH), prolactin (PRL), and the thyroid-stimulating hormone beta subunit (TSH beta) and acts synergistically with the estrogen receptor (ER) and GATA-binding protein 2 (GATA-2) to induce PRL and TSH beta expression, respectively. The glycoprotein hormone alpha subunit (alpha SU) is the first hormone to be expressed during pituitary development. In addition to being expressed in follicle-stimulating hormone, luteinizing hormone (LH), and TSH cells, alpha SU is reported to co-localize with GH in pituitary cells. These findings have led to the suggestion that the expression of Pit-1 in cells of the alpha SU-based gonadotropin cell lineage might also lead to the expression of GH. In this study, we transfected HP 75 cells (derived from a human non-functioning pituitary adenoma that expressed alpha SU and LH beta) with Pit-1 by using an adenovirus FLAG-Pit-1 construct. Most of the transfected cells expressed GH mRNA, with fewer cells expressing PRL and TSH beta mRNA. The HP 75 cells expressed the genes for ER and GATA-2, thus allowing their expression of GH, PRL, and TSH beta mRNA in response to Pit-1. These results support the hypothesis that GH can be induced in cells that possess an active alpha SU gene and shed light on the basic molecular mechanism that drives the development of GH, PRL, and TSH beta expression in the alpha SU-based gonadotroph lineage.
Miyai
Shunsuke
S
Department of Pathology, Tokai University School of Medicine, Bohseidai Isehara Campus, Kanagawa 259-1193, Japan. osamura@is.icc.u-tokai.ac.jp
Yoshimura
Shinichi
S
Iwasaki
Yasumasa
Y
Takekoshi
Susumu
S
Lloyd
Ricardo V
RV
Osamura
Robert Yoshiyuki
RY
D000236:Adenoma / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D019070:Cell Lineage; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics / Q000378:metabolism; D019382:Human Growth Hormone / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010902:Pituitary Gland / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D037322:Thyrotropin, beta Subunit / Q000235:genetics / Q000378:metabolism*; D050817:Transcription Factor Pit-1 / Q000235:genetics / Q000378:metabolism*
D050989:GATA2 Transcription Factor; D015292:Glycoprotein Hormones, alpha Subunit; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D037322:Thyrotropin, beta Subunit; D050817:Transcription Factor Pit-1; D019382:Human Growth Hormone; D011388:Prolactin