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Insight into integrated control of pituitary function revealed through analysis of Musashi target mRNAs

ABSTRACT: The anterior pituitary is comprised of distinct cell types that each secrete specific hormones to control a variety of biological processes including growth, metabolism, reproduction and stress responses. The anterior pituitary shows a remarkable level of cell type plasticity that allows shifts in hormone producing populations to meet organismal demands. Pituitary cell plasticity is tightly regulated and both deficiency in cell plasticity and excessive cell plasticity are associated with common pituitary pathologies. The molecular mechanisms underlying this plasticity are not well characterized but recent work has implicated the stem cell determinants and sequence-specific mRNA binding proteins of the Musashi family as regulators of adult pituitary hormone production. In this study we have sought to identify the full range of Musashi target mRNAs in the adult mouse pituitary. Using Musashi RNA immunoprecipitation we identify a cohort of 1192 mRNAs that show specific Musashi binding. These include mRNAs restricted to discrete hormone-producing cell lineages as well as mRNAs associated with stem and progenitor cells. The processes influenced by the proteins encoded by the Musashi-associated mRNAs include cellular homeostasis, protein trafficking and secretion, unfolded protein response, endocrine processes and female pregnancy. Functional analysis of validated mRNA regulatory 3' untranslated regions (3’ UTRs) reveals UTR-specific positive or negative control by the Musashi proteins within the same cellular context. Together, our findings indicate a broad role for Musashi proteins in the control of pituitary function.

ORGANISM(S): Mus musculus

PROVIDER: GSE199098 | GEO | 2023/07/31

REPOSITORIES: GEO

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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.

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Insight into integrated control of pituitary function revealed through analysis of Musashi target mRNAs

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