title: Follicle-stimulating hormone responsiveness in antral follicles from aryl hydrocarbon receptor knockout mice.
abstract: BACKGROUND
  Previous studies have demonstrated that pre-pubertal aryl hydrocarbon receptor knockout (AHRKO) mice have slow antral follicle growth and reduced capacity to produce estradiol compared to wild-type (WT) mice. Although previous studies have suggested that this is likely due to a reduced ability of the AHRKO follicles to respond to follicle-stimulating hormone (FSH), this possibility was not directly tested. Thus, the goal of these studies was to test the hypothesis that low FSH responsiveness is responsible for the slow growth and reduced estradiol production observed in pre-pubertal AHRKO versus WT antral follicles.
  
  
  METHODS
  Antral follicles from WT and AHRKO mice were cultured with varying amounts of FSH (0-15 IU/mL) for up to 7 days, and subjected to measurements of growth, FSH receptor and steroidogenic regulator expression, sex steroid hormone levels, and inhibin beta-A expression. General linear models (GLM) for repeated measures were used to compare follicle diameters over time among treatments. If the global tests from GLM were significant, Tukey's tests were used for pairwise comparisons. Remaining comparisons among groups were performed using one-way analysis of variance followed by Tukey's post hoc test.
  
  
  RESULTS
  The results indicate that FSH stimulated growth in both WT and AHRKO follicles, but that high levels of FSH (10-15 IU/mL) were required for AHRKO follicles to reach maximal growth, whereas lower levels of FSH (5 IU/mL) were required for WT follicles to reach maximal growth. Further, FSH stimulated expression of FSH receptor, steroidogenic factors, and inhibin beta-A as well as production of steroid hormones in both WT and AHRKO follicles, but the degree of stimulation differed between WT and AHRKO follicles. Interestingly, FSH treatment increased expression of FSH receptor, some steroidogenic regulators, inhibin beta-A, and steroid hormone production more in AHRKO follicles compared to WT follicles.
  
  
  CONCLUSIONS
  Collectively, these data suggest that the slow growth, but not reduced steroidogenesis in AHRKO follicles, is due to their reduced ability to respond to FSH compared to WT follicles. These data also suggest that the AHR may contribute to the ability of FSH to stimulate proper follicle growth, but it may not contribute to FSH-induced steroidogenesis.
authors.affiliation: Department of Comparative Biosciences, University of Illinois, Urbana-Champaign, Illinois 61802, USA.
authors.forename: Isabel
authors.initials: I
authors.lastname: Hernández-Ochoa
authors.forename: Liying
authors.initials: L
authors.lastname: Gao
authors.forename: Jackye
authors.initials: J
authors.lastname: Peretz
authors.forename: Mallikarjuna S
authors.initials: MS
authors.lastname: Basavarajappa
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Bunting
authors.forename: Bethany N
authors.initials: BN
authors.lastname: Karman
authors.forename: Tessie
authors.initials: T
authors.lastname: Paulose
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Flaws
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D028322:Inhibin-beta Subunits / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006080:Ovarian Follicle / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000172:deficiency* / Q000235:genetics; D011962:Receptors, FSH / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D046509:Tissue Culture Techniques; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; D018336:Receptors, Aryl Hydrocarbon; D011962:Receptors, FSH; C103008:inhibin beta A subunit; D000098682:Steroidogenic Acute Regulatory Protein; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D028322:Inhibin-beta Subunits
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