Antiproliferative action of calcitonin on lactotrophs of the rat anterior pituitary gland:: Evidence for the involvement of transforming growth factor β1 in calcitonin action

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-beta1 is an autocrine inhibitor of lactotroph cell proliferation, we investigated a possibility that calcitonin (CT) interacts with TGF-beta1 to inhibit lactotroph cell proliferation. The actions of CT on GGH3 cell proliferation were examined in the absence or presence of anti-TGF-beta1 serum. Subsequent experiments tested the effects of CT on TGF-beta1 mRNA abundance as well as TGF-beta1 synthesis. The studies also tested whether the stimulatory action of CT on TGF-beta1 mRNA expression involves stabilization of TGF-beta1 mRNA. Finally, the experiments investigated in vivo actions of CT on TGF-beta1 synthesis in the AP gland. This was accomplished by studying the changes induced by iv administered CT in TGF-beta1-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-beta1 serum. Moreover, CT stimulated TGF-beta1 mRNA expression, as well as TGF-beta1 synthesis, in a dose-dependent fashion. Stimulatory action of CT on TGF-beta1 expression may be posttranscriptional, because it significantly increased TGF-beta1 mRNA stability. When administered in vivo, CT significantly increased TGF-beta1-immunopositive cell populations of adult female rat AP gland. Colocalization studies for prolactin and TGF-beta1 suggest that CT increased TGF-beta1 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-beta1 expression.