García M D, Casanueva F F, Diéguez C, Señarís R M
Department of Physiology and Department of Medicine, Faculty of Medicine, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain.
Biol Reprod. 2000 Mar;62(3):698-703. doi: 10.1095/biolreprod62.3.698.
Serum leptin levels were significantly increased during rat gestation. Our data showed that leptin mRNA levels in both the adipose tissue and placenta were higher as pregnancy progressed, suggesting a role for both tissues in the hyperproduction of leptin. This paradoxical increase in leptin concentration during gestation suggests that a physiological state of leptin resistance may exist at the hypothalamic level that may explain the hyperphagia observed in pregnant rats. In order to study this issue further, levels of the mRNA encoding the different leptin receptor isoforms were determined in the hypothalamus of pregnant and nonpregnant rats. We found a specific reduction of the mRNA levels encoding the leptin receptor isoform Ob-Rb in the hypothalamus of pregnant rats compared to nonpregnant animals, suggesting that during pregnancy the hypothalamus shows a physiological resistance to the high levels of leptin due, at least in part, to a decrease in the expression of the long, biologically active form of the leptin receptor (Ob-Rb). During lactation, serum leptin levels returned to values observed in nonpregnant rats. In the hypothalami of these animals, Ob-Rb mRNA content was similar to that observed in nonpregnant rats, but we found an increased expression of some of the short forms of the leptin receptor (Ob-Re and Ob-Rf). This could contribute to induction of the hyperphagia present during lactation. These data provide new insights into the adaptive mechanisms that take place during pregnancy and lactation in order to meet increased metabolic requirements.
在大鼠妊娠期间,血清瘦素水平显著升高。我们的数据显示,随着妊娠进展,脂肪组织和胎盘内的瘦素mRNA水平均升高,表明这两种组织在瘦素的过量产生中均发挥作用。妊娠期间瘦素浓度的这种反常增加表明,下丘脑水平可能存在瘦素抵抗的生理状态,这可能解释了在妊娠大鼠中观察到的食欲亢进现象。为了进一步研究这个问题,我们测定了妊娠和未妊娠大鼠下丘脑内编码不同瘦素受体亚型的mRNA水平。我们发现,与未妊娠动物相比,妊娠大鼠下丘脑内编码瘦素受体亚型Ob-Rb的mRNA水平特异性降低,这表明在妊娠期间,下丘脑至少部分由于瘦素受体的长链生物活性形式(Ob-Rb)表达降低而对高水平瘦素表现出生理抵抗。在哺乳期,血清瘦素水平恢复到未妊娠大鼠时观察到的值。在这些动物的下丘脑内,Ob-Rb mRNA含量与未妊娠大鼠相似,但我们发现瘦素受体的一些短链形式(Ob-Re和Ob-Rf)表达增加。这可能有助于引发哺乳期出现的食欲亢进。这些数据为妊娠和哺乳期为满足增加的代谢需求而发生的适应性机制提供了新的见解。