title: Antiproliferative action of calcitonin on lactotrophs of the rat anterior pituitary gland: evidence for the involvement of transforming growth factor beta 1 in calcitonin action.
abstract: Calcitonin-like pituitary peptide, which is synthesized and secreted by gonadotrophs of the rat anterior pituitary (AP) gland, is a potent inhibitor of prolactin biosynthesis and lactotroph cell proliferation. Because TGF-beta 1 is an autocrine inhibitor of lactotroph cell proliferation, we investigated a possibility that calcitonin (CT) interacts with TGF-beta 1 to inhibit lactotroph cell proliferation. The actions of CT on GGH3 cell proliferation were examined in the absence or presence of anti-TGF-beta 1 serum. Subsequent experiments tested the effects of CT on TGF-beta 1 mRNA abundance as well as TGF-beta 1 synthesis. The studies also tested whether the stimulatory action of CT on TGF-beta 1 mRNA expression involves stabilization of TGF-beta 1 mRNA. Finally, the experiments investigated in vivo actions of CT on TGF-beta 1 synthesis in the AP gland. This was accomplished by studying the changes induced by i.v. administered CT in TGF-beta 1-immunopositive cell populations of adult female rat AP glands. The results have shown that the inhibitory action of CT on proliferation of GGH3 cells was attenuated by rabbit anti-TGF-beta 1 serum. Moreover, CT stimulated TGF-beta 1 mRNA expression, as well as TGF-beta 1 synthesis, in a dose-dependent fashion. Stimulatory action of CT on TGF-beta 1 expression may be posttranscriptional, because it significantly increased TGF-beta 1 mRNA stability. When administered in vivo, CT significantly increased TGF-beta 1-immunopositive cell populations of adult female rat AP gland. Colocalization studies for prolactin and TGF-beta 1 suggest that CT increased TGF-beta 1 synthesis in lactotrophs, and possibly in nonlactotroph cell populations. These results suggest that antiproliferative action of CT on lactotrophs may, at least in part, be mediated by CT-induced TGF-beta 1 expression.
authors.affiliation: Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, Texas 79106, USA.
authors.forename: Yong Qing
authors.initials: YQ
authors.lastname: Wang
authors.forename: Ren
authors.initials: R
authors.lastname: Yuan
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Sun
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Lee
authors.forename: Girish V
authors.initials: GV
authors.lastname: Shah
mesh_terms: D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D010903:Pituitary Gland, Anterior / Q000166:cytology* / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D016212:Transforming Growth Factor beta / Q000502:physiology*; D053773:Transforming Growth Factor beta1
chemical_list: D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D011388:Prolactin; D002116:Calcitonin