Species Comparison of the Role of p38 MAP Kinase in the Female Reproductive System

被引:10
作者
Radi, Zaher A. [1 ]
Marusak, Rosemary A. [2 ]
Morris, Dale L. [1 ]
机构
[1] Pfizer Global R&D, Drug Safety Res & Dev, St Louis, MO 63017 USA
[2] N Carolina State Univ, Raleigh, NC 27606 USA
关键词
p38; MAPK; female; reproduction; ACTIVATED PROTEIN-KINASE; ESTROGEN-RECEPTOR-ALPHA; ENDOMETRIAL STROMAL CELLS; GONADOTROPIN-RELEASING-HORMONE; MESSENGER-RNA EXPRESSION; FACTOR BINDING PROTEIN-1; OVARIAN-CANCER CELLS; SMOOTH-MUSCLE-CELLS; C-FOS EXPRESSION; RAT UTERUS;
D O I
10.1293/tox.22.109
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
The p38 mitogen-activated protein kinases (MAPKs) are members of discrete signal transduction pathways that have significant regulatory roles in a variety of biological processes, depending on the cell, tissue and organ type. p38 MAPKs are involved in inflammation, cell growth and differentiation and cell cycle. In the female reproductive system, p38 MAPKs are known to regulate various aspects of the reproductive process such as mammalian estrous and menstrual cycles as well as early pregnancy and parturition. p38 MAPKs have also been implicated in alterations and pathologies observed in the female reproductive system. Therefore, pharmacologic modulation of p38 MAPKs, and inter-connected signaling pathways (e. g., estrogen receptor signaling, c-fos, c-jun), may influence reproductive physiology and function. This article provides a critical, comparative review of available data on the roles of p38 MAPKs in the mammalian female reproductive system and in reproductive pathophysiology in humans and preclinical species. We first introduce fundamental differences and similarities of the mammalian female reproductive system that should be considered by toxicologists and toxicologic pathologists when assessing the effects of new pharmacologic agents on the female reproductive system. We then explore in detail the known roles for p38 MAPKs and related molecules in female reproduction. This foundation is then extended to pathological conditions in which p38 MAPKs are thought to play an integral role. (J Toxicol Pathol 2009; 22: 109-124)
引用
收藏
页码:109 / 124
页数:16
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