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Antiproliferative Action of Calcitonin on Lactotrophs of the Rat Anterior Pituitary Gland: Evidence for the Involvement of Transforming Growth Factor ß1 in Calcitonin Action

Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, Texas 79106

Address all correspondence and requests for reprints to: Girish V. Shah, Ph.D., Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, 1300 Coulter, Amarillo, Texas 79106. E-mail: girish.shah{at}ttuhsc.edu.

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-ß1 is an autocrine inhibitor of lactotroph cell proliferation, we investigated a possibility that calcitonin (CT) interacts with TGF-ß1 to inhibit lactotroph cell proliferation.

The actions of CT on GGH3 cell proliferation were examined in the absence or presence of anti-TGF-ß1 serum. Subsequent experiments tested the effects of CT on TGF-ß1 mRNA abundance as well as TGF-ß1 synthesis. The studies also tested whether the stimulatory action of CT on TGF-ß1 mRNA expression involves stabilization of TGF-ß1 mRNA. Finally, the experiments investigated in vivo actions of CT on TGF-ß1 synthesis in the AP gland. This was accomplished by studying the changes induced by iv administered CT in TGF-ß1-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-ß1 serum. Moreover, CT stimulated TGF-ß1 mRNA expression, as well as TGF-ß1 synthesis, in a dose-dependent fashion. Stimulatory action of CT on TGF-ß1 expression may be posttranscriptional, because it significantly increased TGF-ß1 mRNA stability. When administered in vivo, CT significantly increased TGF-ß1-immunopositive cell populations of adult female rat AP gland. Colocalization studies for prolactin and TGF-ß1 suggest that CT increased TGF-ß1 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-ß1 expression.