Buhimschi I A, Yallampalli C, Buhimschi C S, Saade G R, Garfield R E
The University of Texas Medical Branch, Department of Obstetrics and Gynaecology, Division of Reproductive Sciences, Galveston, Texas, USA.
Mol Hum Reprod. 2000 May;6(5):404-14. doi: 10.1093/molehr/6.5.404.
It has previously been reported that uterine nitric oxide (NO) production is enhanced during rat pregnancy compared to non-pregnant, labouring or postpartum states. The present hypothesis is that these changes in uterine NO production during pregnancy are caused by the interplay of oestrogen and progesterone. It is further postulated that changes in cyclic guanosine monophosphate (cGMP) production closely follow the changes in uterine NO synthesis. To test these hypotheses a variety of hormonal regimens (17beta-oestradiol, progesterone and combinations) were applied to different rat models (prepubertal, non-pregnant intact and ovariectomized as well as pregnant rats). The production of nitric oxide (NO) as well as basal and in-vitro NO-stimulated cGMP tissue content were measured in parallel. NO production was measured by the accumulation of nitrites and nitrates in a 24 h incubation medium as analysed by Greiss reaction. cGMP content was measured by radioimmunoassay. Diethylenetriamine/NO (DETA/NO) was used as NO donor. NO production in the rat uterus was markedly increased by pregnancy compared to other physiological (prepubertal, or cycling dioestrus) and experimentally induced (OVX) states. In contrast, uterine cGMP was significantly decreased in pregnancy. Pregnancy also inhibited the elevation in uterine cGMP after in-vitro NO challenge. Chronic 17beta-oestradiol treatment in prepubertal and/or OVX models increased NO production and also mimicked the effect of pregnancy on cGMP. Administration of progesterone in prepubertal rats induced a parallel decrease in both uterine NO and cGMP. In conclusion, sex steroid hormones distinctly regulate uterine NO and cGMP production depending upon the dose and regimen used, as well as the animal's reproductive state.
先前已有报道称，与未怀孕、分娩或产后状态相比，大鼠怀孕期间子宫一氧化氮（NO）的生成会增强。目前的假说是，怀孕期间子宫NO生成的这些变化是由雌激素和孕酮的相互作用引起的。进一步推测，环磷酸鸟苷（cGMP）生成的变化与子宫NO合成的变化密切相关。为了验证这些假说，将多种激素方案（17β-雌二醇、孕酮及其组合）应用于不同的大鼠模型（青春期前、未怀孕的完整大鼠、去卵巢大鼠以及怀孕大鼠）。同时测量了一氧化氮（NO）的生成以及基础和体外NO刺激后的cGMP组织含量。通过格里斯反应分析24小时孵育培养基中亚硝酸盐和硝酸盐的积累来测量NO生成。通过放射免疫测定法测量cGMP含量。二乙烯三胺/NO（DETA/NO）用作NO供体。与其他生理状态（青春期前或发情周期的间情期）和实验诱导状态（去卵巢）相比，怀孕显著增加了大鼠子宫中的NO生成。相比之下，怀孕期间子宫cGMP显著降低。怀孕还抑制了体外NO刺激后子宫cGMP的升高。在青春期前和/或去卵巢模型中进行慢性17β-雌二醇治疗可增加NO生成，并且也模拟了怀孕对cGMP的影响。在青春期前大鼠中给予孕酮会导致子宫NO和cGMP同时下降。总之，性甾体激素根据所用的剂量和方案以及动物的生殖状态，对子宫NO和cGMP的生成有明显的调节作用。
