Wang Yong Qing, Yuan Ren, Sun Ya-Ping, Lee Tae-Jin, Shah Girish V
Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, Texas 79106, USA.
Endocrinology. 2003 May;144(5):2164-71. doi: 10.1210/en.2002-220740.
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.
降钙素样垂体肽由大鼠垂体前叶（AP）的促性腺激素细胞合成并分泌，是催乳素生物合成和催乳素细胞增殖的有效抑制剂。由于转化生长因子β1（TGF-β1）是催乳素细胞增殖的自分泌抑制剂，我们研究了降钙素（CT）与TGF-β1相互作用以抑制催乳素细胞增殖的可能性。在存在或不存在抗TGF-β1血清的情况下，检测了CT对GGH3细胞增殖的作用。随后的实验测试了CT对TGF-β1 mRNA丰度以及TGF-β1合成的影响。这些研究还测试了CT对TGF-β1 mRNA表达的刺激作用是否涉及TGF-β1 mRNA的稳定性。最后，实验研究了CT对AP腺中TGF-β1合成的体内作用。这是通过研究静脉注射CT对成年雌性大鼠AP腺中TGF-β1免疫阳性细胞群体的诱导变化来实现的。结果表明，兔抗TGF-β1血清减弱了CT对GGH3细胞增殖的抑制作用。此外，CT以剂量依赖性方式刺激TGF-β1 mRNA表达以及TGF-β1合成。CT对TGF-β1表达的刺激作用可能是转录后作用，因为它显著增加了TGF-β1 mRNA的稳定性。当在体内给药时，CT显著增加了成年雌性大鼠AP腺中TGF-β1免疫阳性细胞群体。催乳素和TGF-β1的共定位研究表明，CT增加了催乳素细胞以及可能在非催乳素细胞群体中TGF-β1的合成。这些结果表明，CT对催乳素细胞的抗增殖作用可能至少部分是由CT诱导的TGF-β1表达介导的。
