Noskova Vera, Bottalico Barbara, Olsson Hanna, Ehinger Anna, Pilka Radovan, Casslén Bertil, Hansson Stefan R
Department of Obstetrics and Gynecology, Lund University Hospital, Lund, Sweden.
Mol Hum Reprod. 2006 Aug;12(8):483-9. doi: 10.1093/molehr/gah259. Epub 2006 Mar 27.
Cellular reuptake of monoamines, which is mediated by cell membrane transporters, is followed by accumulation in vesicles by vesicular monoamine transporters (VMAT). The aim of this study was to demonstrate the presence of functional monoamine transporters with high affinity for histamine in human endometrial tissue, since histamine has been implicated as a paracrine signal during endometrial decidualization and embryo implantation. In situ hybridization with (35)S-labelled cRNA probes was used for detection of the organic cationic transporter-2 (OCT-2), the extraneuronal monoamine transporter (EMT), and VMAT-2 in cryosections of normal human endometrial tissue. To identify functional transporters for histamine in endometrial cells, we incubated primary cultures of stromal cells and cultures of attached glands with (3)H-labelled histamine. Cultures were pretreated with either corticosterone, a specific inhibitor of EMT, or reserpine, a specific inhibitor of VMAT-2. EMT mRNA was localized in the stroma with peak expression in the secretory phase, whereas OCT-2 mRNA was expressed by few cells in the stroma throughout the cycle. VMAT-2 mRNA was localized in the stroma during the proliferative phase and in the epithelium during the secretory phase. Thus, EMT and VMAT-2, which both have high affinity for histamine, are strongly expressed in endometrial cells. Both corticosterone and reserpine significantly reduced the uptake of (3)H-histamine in stromal cells during the proliferative as well as the secretory phase. This indicates the presence of functional EMT and VMAT-2 transporter proteins throughout the cycle, even though their periods of maximal mRNA expression were limited. The results of uptake experiments with glandular epithelial cells confirmed not only the presence of functional VMAT-2 transporter protein in the secretory phase but also the absence of a histamine-specific plasma membrane transporter throughout the cycle. Thus, endometrial tissue contains both plasma membrane and vesicular membrane monoamine transporters with high affinity for histamine. They can potentially influence the reproductive process by the uptake of extracellular histamine and subsequent release on demand.
单胺的细胞再摄取由细胞膜转运体介导，随后通过囊泡单胺转运体（VMAT）在囊泡中积累。本研究的目的是证明人子宫内膜组织中存在对组胺具有高亲和力的功能性单胺转运体，因为组胺被认为是子宫内膜蜕膜化和胚胎着床过程中的旁分泌信号。使用（35）S标记的cRNA探针进行原位杂交，以检测正常人子宫内膜组织冰冻切片中的有机阳离子转运体-2（OCT-2）、非神经元单胺转运体（EMT）和VMAT-2。为了鉴定子宫内膜细胞中组胺的功能性转运体，我们用（3）H标记的组胺孵育基质细胞原代培养物和附着腺体的培养物。培养物用EMT的特异性抑制剂皮质酮或VMAT-2的特异性抑制剂利血平进行预处理。EMT mRNA定位于基质中，在分泌期表达达到峰值，而OCT-2 mRNA在整个周期中仅由基质中的少数细胞表达。VMAT-2 mRNA在增殖期定位于基质中，在分泌期定位于上皮中。因此，对组胺均具有高亲和力的EMT和VMAT-2在子宫内膜细胞中强烈表达。皮质酮和利血平在增殖期和分泌期均显著降低了基质细胞对（3）H-组胺的摄取。这表明在整个周期中都存在功能性的EMT和VMAT-2转运体蛋白，尽管它们的mRNA最大表达期是有限的。腺上皮细胞摄取实验的结果不仅证实了分泌期功能性VMAT-2转运体蛋白的存在，而且还证实了在整个周期中不存在组胺特异性质膜转运体。因此，子宫内膜组织同时含有对组胺具有高亲和力的质膜和囊泡膜单胺转运体。它们可能通过摄取细胞外组胺并随后按需释放来潜在地影响生殖过程。
