McFarland-Mancini Molly, Hugo Eric, Loftus Jean, Ben-Jonathan Nira
Department of Cell Biology, University of Cincinnati Medical School, Cincinnati, OH 45267-0521, USA.
Biochem Biophys Res Commun. 2006 May 26;344(1):9-16. doi: 10.1016/j.bbrc.2006.03.168.
In addition to the pituitary, prolactin (PRL) in humans is produced at non-pituitary sites where it acts as a cytokine. We previously reported that PRL is expressed and released from breast adipose explants, raising the question as to the dynamics of its production and its regulation. Preadipocytes were isolated from breast adipose tissue obtained during breast reduction. PRL expression was transiently increased during early preadipocyte differentiation. Both isoproterenol, a beta-adrenergic receptor agonist, and PACAP, pituitary adenylate cyclase activating peptide, increased PRL expression, and release from preadipocytes. This stimulation was suppressed by several protein kinase inhibitors, suggesting involvement of multiple signaling pathways. Transfection of preadipocytes with a superdistal PRL promoter/luciferase reporter revealed two stimulatory domains and an inhibitory domain. These data establish the transcriptional regulation of adipocyte PRL by the superdistal PRL promoter, its transient expression during adipogenesis, and the stimulatory effect of catecholamines and PACAP.
除垂体外，人类催乳素（PRL）还在非垂体部位产生，在这些部位它作为一种细胞因子发挥作用。我们之前报道过PRL由乳腺脂肪外植体表达和释放，这就引发了其产生动态及调控方面的问题。从乳房缩小手术中获取的乳腺脂肪组织中分离出前脂肪细胞。在前脂肪细胞早期分化过程中，PRL表达短暂增加。β-肾上腺素能受体激动剂异丙肾上腺素和垂体腺苷酸环化酶激活肽（PACAP）均能增加PRL表达，并促进前脂肪细胞释放PRL。这种刺激被几种蛋白激酶抑制剂抑制，提示涉及多种信号通路。用超远端PRL启动子/荧光素酶报告基因转染前脂肪细胞，发现了两个刺激结构域和一个抑制结构域。这些数据证实了超远端PRL启动子对脂肪细胞PRL的转录调控、其在脂肪生成过程中的短暂表达以及儿茶酚胺和PACAP的刺激作用。
