Rillema J A, Rowady D L
Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Proc Soc Exp Biol Med. 1996 Jun;212(2):142-6. doi: 10.3181/00379727-212-44001.
The signal transduction pathway(s) for the prolactin (PRL) regulation of lactogenic processes in the mammary are not fully known. Recent studies indicate that the PRL occupancy of its receptor activates a tyrosine kinase (JAK-2), which is constitutively associated with the receptor. In the present studies, we have characterized the PRL stimulation of c-fos mRNA accumulation in mouse mammary gland explants that were precultured with insulin and cortisol for 36 hr. In time course studies, an initial effect (2-fold increase) of PRL was apparent after 15 min, a 4-fold increase occurred after 60 min, and a 2-fold increase was apparent after 2 hr. Dose-response experiments indicated an initial effect with 5 ng/ml PRL and a maximum effect with 500 ng/ml PRL. The accumulation of c-fos; mRNA in the cultured mammary tissues was also increased by human GH, recombinant bovine PRL, cycloheximide, and phorbol 12-myristate 13-acetate (TPA). The cycloheximide and PRL responses were additive, thus indicating that cycloheximide did not "superinduce" the PRL stimulation of c-fos mRNA accumulation. Downregulation of protein kinase C (PKC) by pretreating mammary tissues for 1 day with TPA did not affect the magnitude of the PRL stimulation of c-fos mRNA accumulation. The findings from these studies are consistent with c-fos playing a role in the PRL stimulation of lactogenic processes in the mammary gland. PRL had no effect on c-jun mRNA accumulation under any of the experimental conditions employed in the c-fos studies.
催乳素（PRL）对乳腺泌乳过程的信号转导途径尚未完全明确。最近的研究表明，PRL与其受体结合后会激活一种酪氨酸激酶（JAK-2），该激酶与受体组成性相关。在本研究中，我们对用胰岛素和皮质醇预培养36小时的小鼠乳腺外植体中PRL刺激c-fos mRNA积累的情况进行了表征。在时间进程研究中，PRL的初始效应（增加2倍）在15分钟后明显，60分钟后增加4倍，2小时后增加2倍。剂量反应实验表明，5 ng/ml PRL有初始效应，500 ng/ml PRL有最大效应。人生长激素、重组牛PRL、环己酰亚胺和佛波醇12-肉豆蔻酸酯13-乙酸酯（TPA）也可增加培养乳腺组织中c-fos mRNA的积累。环己酰亚胺和PRL的反应是相加的，因此表明环己酰亚胺不会“超诱导”PRL对c-fos mRNA积累的刺激。用TPA预处理乳腺组织1天对蛋白激酶C（PKC）的下调并不影响PRL对c-fos mRNA积累刺激的幅度。这些研究结果与c-fos在PRL刺激乳腺泌乳过程中发挥作用一致。在c-fos研究中采用的任何实验条件下，PRL对c-jun mRNA积累均无影响。
