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Ept7 influences estrogen action in the pituitary gland and body weight of rats.

ABSTRACT: 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 17?-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.

SUBMITTER: Kurz SG

PROVIDER: S-EPMC4035442 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Ept7 influences estrogen action in the pituitary gland and body weight of rats.

Kurz Scott G SG Dennison Kirsten L KL Samanas Nyssa Becker NB Hickman Maureen Peters MP Eckert Quincy A QA Walker Tiffany L TL Cupp Andrea S AS Shull James D JD

Mammalian genome : official journal of the International Mammalian Genome Society 20140122 5-6

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, ...[more]

PMID: 24448715

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Project description:Several processes governing growth and metabolism are regulated by the neuroendocrine system, particularly the trophic hormones produced in the anterior pituitary gland. However, many of the differences that exist in pituitary gene expression and functional gene networks associated with divergent growth characteristics are still largely unknown. Using the Del-Mar 14K Chicken Integrated Systems microarray, this experiment evaluated global gene expression in the anterior pituitary gland during the first 7 weeks of post-hatch growth in two lines of chickens genetically selected for high growth (HG) or low growth (LG) at SRA-INRA, France. The HG and LG chickens differ in body weight, abdominal fat content, and plasma hormone and metabolite levels, making them a valuable model for both biomedical and agricultural traits. Amplified total RNA extracted from individual anterior pituitary glands collected from 4 birds from each line at each age (n=4) was produced. Cy-3 labeled cDNA from these samples was hybridized with an aliquot of Cy-5 labeled cDNA made from a pool of total RNA from all 32 samples. Data were analyzed as log2-(Cy3intensity (norm)/Cy5intensity (raw)) by two-way ANOVA using a linear mixed model procedure (PROC MIXED; SAS institute Inc., Cary, NC), and a total of 2,310 spots were significantly different (P<0.05) by line (1,100), age (1,058), or the line-by-age interaction (353). Of these, we identified 291 spots representing 263 genes as differentially expressed between HG and LG birds, where there was a >160% difference between the highest expression in one line and the lowest expression in the other and a significant line-by-age (110) or line (181) effect. Four anterior pituitary hormones were contained in this set of differentially expressed genes: thyroid-stimulating hormone ?-subunit, luteinizing hormone ?-subunit, and follicle-stimulating hormone ?-subunit mRNA levels were higher in the HG line; and growth hormone mRNA was elevated in the LG line. Pathway analysis revealed differences in expression between HG and LG lines associated with molecular transport, endocrine system development and function, organ and tissue morphology, and cellular compromise. Potential alteration in pituitary function between the two lines was highlighted in a network containing genes associated with hormone expression and secretion, as well as those potentially involved in pituitary gland morphology and vascularization.

Project description:BackgroundThough intensive genetic selection has led to extraordinary advances in growth rate and feed efficiency in production of meat-type chickens, endocrine processes controlling these traits are still poorly understood. The anterior pituitary gland is a central component of the neuroendocrine system and plays a key role in regulating important physiological processes that directly impact broiler production efficiency, though how differences in pituitary gland function contribute to various growth and body composition phenotypes is not fully understood.ResultsGlobal anterior pituitary gene expression was evaluated on post-hatch weeks 1, 3, 5, and 7 in male broiler chickens selected for high (HG) or low (LG) growth. Differentially expressed genes (DEGs) were analyzed with gene ontology categorization, self-organizing maps, gene interaction network determination, and upstream regulator identification to uncover novel pituitary genes and pathways contributing to differences in growth and body composition. A total of 263 genes were differentially expressed between HG and LG anterior pituitary glands (P ≤ 0.05 for genetic line-by-age interaction or main effect of line; ≥1.6-fold difference between lines), including genes encoding four anterior pituitary hormones. Genes involved in signal transduction, transcriptional regulation, and vesicle-mediated transport were differentially expressed and are predicted to influence expression and secretion of pituitary hormones. DEGs involved in immune regulation provide evidence that inflammation and response to cellular stressors may compromise pituitary function in LG birds, affecting their ability to adequately produce pituitary hormones. Many DEGs were also predicted to function in processes that regulate organ morphology and angiogenesis, suggesting pituitary gland structure differs between the divergently selected lines.ConclusionsThe large number of DEGs within the anterior pituitary gland of birds selected for high or low body weight highlights the importance of this gland in regulating economically important traits such as growth and body composition in broiler chickens. Intracellular signaling, transcriptional regulation, and membrane trafficking are important cellular processes contributing to proper hormone production and secretion. The data also suggest that pituitary function is intimately tied to structure, and organization of the gland could influence hypothalamic and systemic metabolic inputs and delivery of hormones regulating growth and metabolism into peripheral circulation.

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Ept7 influences estrogen action in the pituitary gland and body weight of rats.

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Ept7 influences estrogen action in the pituitary gland and body weight of rats.

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