Kurz Scott G, Dennison Kirsten L, Samanas Nyssa Becker, Hickman Maureen Peters, Eckert Quincy A, Walker Tiffany L, Cupp Andrea S, Shull James D
Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Mamm Genome. 2014 Jun;25(5-6):244-52. doi: 10.1007/s00335-014-9504-4. Epub 2014 Jan 22.
Estrogens control many aspects of pituitary gland biology, including regulation of lactotroph homeostasis and synthesis and secretion of prolactin. In rat models, these actions are strain specific and heritable, and multiple quantitative trait loci (QTL) have been mapped that impact the responsiveness of the lactotroph to estrogens. One such QTL, Ept7, was mapped to RNO7 in female progeny generated in an intercross between BN rats, in which the lactotroph population is insensitive to estrogens, and ACI rats, which develop lactotroph hyperplasia/adenoma and associated hyperprolactinemia in response to estrogen treatment. The primary objective of this study was to confirm the existence of Ept7 and to quantify the impact of this QTL on responsiveness of the pituitary gland of female and male rats to 17β-estradiol (E2) and diethylstilbestrol (DES), respectively. Secondary objectives were to determine if Ept7 influences the responsiveness of the male reproductive tract to DES and to identify other discernible phenotypes influenced by Ept7. To achieve these objectives, a congenic rat strain that harbors BN alleles across the Ept7 interval on the genetic background of the ACI strain was generated and characterized to define the effect of administered estrogens on the anterior pituitary gland and male reproductive tissues. Data presented herein indicate Ept7 exerts a marked effect on development of lactotroph hyperplasia in response to estrogen treatment, but does not affect atrophy of the male reproductive tissues in response to hormone treatment. Ept7 was also observed to exert gender specific effects on body weight in young adult rats.
雌激素控制着垂体生物学的许多方面，包括对催乳素细胞内稳态的调节以及催乳素的合成与分泌。在大鼠模型中，这些作用具有品系特异性且可遗传，并且已经定位了多个影响催乳素细胞对雌激素反应性的数量性状基因座（QTL）。其中一个这样的QTL，即Ept7，在BN大鼠（其催乳素细胞群体对雌激素不敏感）与ACI大鼠（在雌激素处理后会发生催乳素细胞增生/腺瘤及相关的高催乳素血症）杂交产生的雌性后代中被定位到RNO7上。本研究的主要目的是确认Ept7的存在，并量化该QTL对雌性和雄性大鼠垂体分别对17β-雌二醇（E2）和己烯雌酚（DES）反应性的影响。次要目的是确定Ept7是否影响雄性生殖道对DES的反应性，并鉴定受Ept7影响的其他可识别的表型。为实现这些目标，构建了一个在ACI品系遗传背景上跨越Ept7区间携带BN等位基因的近交系大鼠，并对其进行了表征，以确定给予雌激素对垂体前叶和雄性生殖组织的影响。本文提供的数据表明，Ept7对雌激素处理后催乳素细胞增生的发展有显著影响，但不影响激素处理后雄性生殖组织的萎缩。还观察到Ept7对年轻成年大鼠的体重有性别特异性影响。
