title: Expression and localisation of c-kit and KITL in the adult human ovary.
abstract: BACKGROUND
  The c-kit/kit ligand (KITL) signalling axis is an essential component of ovarian folliculogenesis in mammals, but little is known about expression and localisation of its key components in the ovaries of reproductive age women. This study aimed to characterise mRNA expression of c-kit and KITL isoforms and the localisation of c-kit and KITL proteins in adult human premenopausal ovaries.
  
  
  METHODS
  This study utilised granulosa cells obtained from the preovulatory follicles of women undergoing assisted reproduction, pieces of ovarian tissue obtained from premenopausal women undergoing gynaecological surgeries and archival paraffin-embedded premenopausal ovarian tissues. Methodology included PCR for gene expression and Western blot or immunohistochemistry for protein expression.
  
  
  RESULTS
  Both c-kit mRNA isoforms, known as GNNK+ and GNNK-, were detected in human ovarian cortex, while KITL protein isoforms (KITL1 and KITL2) were present in ovarian cortex and human granulosa cells. Immunohistochemistry showed expression of KITL and c-kit protein in multiple cell types within follicles throughout development, from primordial follicles to large antral follicles, in addition to atretic follicles. Oocytes of all follicle stages expressed c-kit protein exclusively. Interestingly, unlike animal models, expression of both proteins displayed a less cell-type specific distribution with immunostaining present in granulosa, theca and stromal cells, suggesting that autocrine signalling occurs within the human ovary.
  
  
  CONCLUSIONS
  The results of this study indicate that c-kit/KITL signalling also occurs in the human ovary, as established in various animal models, and may involve previously unknown autocrine signalling.
authors.affiliation: Robinson Research Institute, School of Paediatrics and Reproductive Health, Adelaide, South Australia, Australia. astrud.tuck@adelaide.edu.au.|Dame Roma Mitchell Cancer Research Laboratories, School of Medicine; University of Adelaide, Adelaide, South Australia, Australia. astrud.tuck@adelaide.edu.au.
authors.forename: Astrud R
authors.initials: AR
authors.lastname: Tuck
authors.affiliation: Robinson Research Institute, School of Paediatrics and Reproductive Health, Adelaide, South Australia, Australia. rebecca.robker@adelaide.edu.au.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Robker
authors.affiliation: Robinson Research Institute, School of Paediatrics and Reproductive Health, Adelaide, South Australia, Australia. robert.norman@adelaide.edu.au.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Norman
authors.affiliation: Dame Roma Mitchell Cancer Research Laboratories, School of Medicine; University of Adelaide, Adelaide, South Australia, Australia. wayne.tilley@adelaide.edu.au.
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Tilley
authors.affiliation: Robinson Research Institute, School of Paediatrics and Reproductive Health, Adelaide, South Australia, Australia. theresa.hickey@adelaide.edu.au.|Dame Roma Mitchell Cancer Research Laboratories, School of Medicine; University of Adelaide, Adelaide, South Australia, Australia. theresa.hickey@adelaide.edu.au.
authors.forename: Theresa E
authors.initials: TE
authors.lastname: Hickey
mesh_terms: D000328:Adult; D019898:Autocrine Communication / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D009865:Oocytes / Q000378:metabolism; D006080:Ovarian Follicle / Q000378:metabolism; D010053:Ovary / Q000254:growth & development / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D019089:Stem Cell Factor / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit