Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA, USA.
Department of Obstetrics/Gynecology/Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
Endocrine. 2016 Dec;54(3):788-797. doi: 10.1007/s12020-016-1145-9. Epub 2016 Oct 21.
We recently demonstrated that offspring delivered to baboons deprived of estrogen during the second half of gestation exhibited insulin resistance prior to onset of puberty. Because gonadal hormones have a profound effect on insulin action and secretion in adults, we determined whether insulin resistance is retained after initiation of gonadal secretion of testosterone and estradiol. Glucose tolerance tests were performed in postpubertal baboon offspring of untreated and letrozole-treated animals (serum estradiol reduced >95 %). Basal fasting levels of insulin (P < 0.05) and peak 1 min and 1 + 3 + 5 min levels of glucose after glucose tolerance tests challenge (P < 0.03) were greater in offspring delivered to letrozole-treated, estrogen-deprived baboons than untreated animals. Moreover, the value for the HOMA-IR, an accepted index of insulin resistance, was 2-fold greater (P < 0.05) in offspring delivered to baboons treated with letrozole than in untreated animals. Collectively these results support the proposal that estrogen normally has an important role in programming mechanisms in utero within the developing fetus that lead to insulin sensitivity after birth.
我们最近的研究表明，在妊娠后半期被剥夺雌激素的狒狒所产下的后代，在青春期前就表现出胰岛素抵抗。由于性腺激素对成年期的胰岛素作用和分泌有深远的影响，我们确定在睾丸分泌睾酮和雌二醇开始后，是否仍存在胰岛素抵抗。在未治疗和来曲唑治疗动物（血清雌二醇降低> 95％）的青春期后狒狒后代中进行了葡萄糖耐量试验。与未经治疗的动物相比，接受来曲唑治疗、雌激素剥夺的狒狒所产下的后代的空腹胰岛素基础水平（P <0.05）和葡萄糖耐量试验后 1 分钟和 1+3+5 分钟的峰值血糖水平（P <0.03）更高。此外，接受来曲唑治疗的狒狒所产下的后代的 HOMA-IR 值（公认的胰岛素抵抗指数）是未治疗动物的 2 倍（P <0.05）。这些结果共同表明，雌激素在宫内发育中的胎儿中具有重要的编程机制作用，可导致出生后胰岛素敏感性。
