title: Estradiol and corticosterone stimulate the proliferation of a GH cell line, MtT/S: Proliferation of growth hormone cells.
abstract: Estrogens are known as a potent growth-stimulator of the anterior pituitary cells such as prolactin cells and somatomammotroph cell lines, while glucocorticoids often inhibit cellular proliferation in the pituitary gland as well as in the extra-pituitary tissues. In this study, the involvement of these steroid hormones in the regulation of proliferation was examined in the MtT/S cells, secreting growth hormone (GH).
  
  
  
  Effects of estrogens and glucocorticoids were examined in MtT/S cells grown in the medium containing dextran-coated charcoal treated serum. The relative cell density after culture was estimated by the Cell Titer-Glo Luminescent Cell Viability Assay System, and the proliferation rate was determined by the BrdU incorporation method. The mRNA levels were determined by real-time PCR.
  
  
  
  Estradiol and the specific agonist for both estrogen receptor (ER) α and ERβ stimulated MtT/S growth at a dose dependent manner. The membrane impermeable estrogen, 17β-estradiol-bovine serum albumin conjugate also stimulated the MtT/S proliferation. The effects of all estrogens were inhibited by an estrogen receptor antagonist, ICI182780. Corticosterone stimulated the proliferation of MtT/S cells at doses lower than 10nM without stimulating GH gene transcription, whereas it did not change the proliferation rate at 1μM. The effects of corticosterone were inhibited by glucocorticoid receptor inhibitor, RU486, but not by the mineralocorticoid receptor antagonist, spironolactone. Both estrogens and glucocorticoids were found to stimulate the proliferation of MtT/S, increasing the mRNA expression of cyclins D1, D3, and E.
  
  
  
  The results suggest that estrogens and glucocorticoids may be involved in the mechanisms responsible for the proliferation of GH cells in the course of pituitary development, to maintain the population of GH cells in the adult pituitary gland, and also in the promotion of GH cell tumors.
authors.affiliation: Laboratory of Molecular Neuroendocrinology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan. Electronic address: hnogami@md.tsukuba.ac.jp.
authors.forename: Haruo
authors.initials: H
authors.lastname: Nogami
authors.affiliation: Department of Anatomy, School of Medicine, Keio University, Tokyo 160-8582, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hiraoka
authors.affiliation: Department of Anatomy, School of Medicine, Keio University, Tokyo 160-8582, Japan.
authors.forename: Sadakazu
authors.initials: S
authors.lastname: Aiso
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D003345:Corticosterone / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D000077267:Fulvestrant; D005938:Glucocorticoids / Q000494:pharmacology*; D013006:Growth Hormone / Q000187:drug effects / Q000235:genetics; D006727:Hormone Antagonists / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D052683:Somatotrophs / Q000187:drug effects* / Q000378:metabolism; D013148:Spironolactone / Q000494:pharmacology
chemical_list: D065171:Estrogen Receptor Antagonists; D004967:Estrogens; D005938:Glucocorticoids; D006727:Hormone Antagonists; D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; C043090:estradiol-bovine serum albumin; D000077267:Fulvestrant; D012710:Serum Albumin, Bovine; D013148:Spironolactone; D015735:Mifepristone; D004958:Estradiol; D013006:Growth Hormone; D003345:Corticosterone
keywords: Cyclin; Estrogens; Glucocorticoids; Growth hormone cells; MtT/S