Graduate School of Nanobioscience, Yokohama City University, Yokohama 236-0027, Japan.
Exp Biol Med (Maywood). 2014 Mar;239(3):311-9. doi: 10.1177/1535370213519722. Epub 2014 Feb 12.
Gonadotrophs in the anterior pituitary secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Neonatal diethylstilbestrol (neoDES) treatment affects reproductive function of male and female mice, but the effect of this treatment on the development as well as direct effects on pituitary gonadotrophs have not been ascertained. We investigated LH-secreting gonadotropes and the expression of genes involved in the synthesis and secretion of gonadotropins in the anterior pituitary of neoDES mice using immunohistochemistry and real-time reverse transcription-polymerase chain reaction (RT-PCR). The percentage of LH-secreting gonadotropes in 90-day-old female mice treated neonatally with an oil vehicle (neoOil) was significantly lower than in 30-day-old neoOil females but not in males, indicating a significant reduction after reproductive maturation in females. The percentage of LH-secreting gonadotropes in the medial area of 90-day-old neoDES females was significantly lower than that of 90-day-old neoOil females, ovariectomized neoOil females, and neoOil and neoDES males. The expression of the LH beta (Lhb) subunit in the anterior pituitary of 90-day-old neoDES females was similar to that in neoOil females, but it was significantly lower than that observed in 90-day-old males. Ovariectomy increased the expression of the alpha subunit of glycoprotein hormones, FSH beta (Fshb) subunit and Lhb subunit both in neoOil and neoDES females, suggesting that the anterior pituitary of neoDES female mice is regulated by ovarian hormones via negative feedback. In organ-cultured, anterior pituitaries exposed to DES exhibited no change in the number of LH-secreting gonadotropes but did reduced gene expression. These results suggest that LH-secreting gonadotropes in the female mice are not only directly affected by neoDES but also are influenced by the masculinization of the hypothalamus. That is, neonatal DES exposure can masculinize or defeminize the hypothalamus of female mice. However, the regulation of the pituitary gonadotropins by the hypothalamus could be different from that in intact male mice.
垂体前叶的促性腺激素分泌黄体生成素 (LH) 和卵泡刺激素 (FSH)。新生去乙底酚（neoDES）处理会影响雄性和雌性小鼠的生殖功能，但这种处理对垂体促性腺激素的发育以及对其直接影响尚未确定。我们使用免疫组织化学和实时逆转录聚合酶链反应 (RT-PCR) 研究了 neoDES 小鼠垂体前叶的 LH 分泌促性腺细胞和参与促性腺激素合成和分泌的基因表达。用油载体（neoOil）处理的 90 日龄雌性小鼠的 LH 分泌促性腺细胞的百分比明显低于 30 日龄 neoOil 雌性小鼠，但不低于雄性小鼠，表明雌性小鼠在生殖成熟后明显减少。90 日龄 neoDES 雌性小鼠内侧区 LH 分泌促性腺细胞的百分比明显低于 90 日龄 neoOil 雌性小鼠、卵巢切除 neoOil 雌性小鼠以及 neoOil 和 neoDES 雄性小鼠。90 日龄 neoDES 雌性小鼠垂体前叶 Lhb 亚基的表达与 neoOil 雌性小鼠相似，但明显低于 90 日龄雄性小鼠。卵巢切除术增加了糖蛋白激素 α 亚基、Fshb 亚基和 Lhb 亚基在 neoOil 和 neoDES 雌性小鼠中的表达，表明 neoDES 雌性小鼠的垂体前叶通过负反馈受卵巢激素的调节。在器官培养中，暴露于 DES 的垂体前叶的 LH 分泌促性腺细胞数量没有变化，但基因表达减少。这些结果表明，雌性小鼠的 LH 分泌促性腺细胞不仅直接受到 neoDES 的影响，而且还受到下丘脑去性别化的影响。也就是说，新生 DES 暴露可以使雌性小鼠的下丘脑雄性化或去性别化。然而，下丘脑对垂体促性腺激素的调节可能与完整雄性小鼠不同。
