title: The effect of flutamide on expression of androgen and estrogen receptors in the gubernaculum and surrounding structures during testicular descent.
abstract: OBJECTIVE
  Inguinoscrotal testicular descent is controlled by androgens between embryonic days E16-19, but androgen receptor (AR) and estrogen receptor (ER) locations are unknown. We aimed to find AR, ERα, and ERβ in the gubernaculum and inguinal fat pad (IFP) in normal rats and after flutamide treatment.
  
  
  METHODS
  Sprague-Dawley timed-mated rats were injected with flutamide (75 mg/kg body weight/5% ethanol + oil) on E16-19 or vehicle alone. Male fetuses or pups (5-10/group) were collected at E16; E19; and postnatal (P) days 0, 2, 4, 8. Sections were prepared for hematoxylin and eosin or immunohistochemistry for AR, ERα, and ERβ. Receptor labeling was quantitated as distinct nuclear labeling/100 μm(2) in gubernaculum and IFP.
  
  
  RESULTS
  There was minimal gubernacular AR-labeling until E19, dramatically increasing postnatally. By contrast, at E16-E19 there was significant IFP AR immunoreactivity suppressed by flutamide (P < .05). No ERα expression was observed, but ERβ was expressed in both gubernaculum and IFP, maximally at E16, but unchanged by flutamide.
  
  
  CONCLUSIONS
  During the androgen sensitivity window (E16-19), the gubernaculum contains ERβ but minimal ERα or AR, while the IFP, which is supplied by the genitofemoral nerve, contains abundant AR that are flutamide-sensitive. These results suggest that the IFP could be the site of androgenic action controlling gubernacular development.
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Tamara R
authors.initials: TR
authors.lastname: Nation
authors.forename: Silverton
authors.initials: S
authors.lastname: Buraundi
authors.forename: Adam
authors.initials: A
authors.lastname: Balic
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Farmer
authors.forename: Don
authors.initials: D
authors.lastname: Newgreen
authors.forename: Bridget R
authors.initials: BR
authors.lastname: Southwell
authors.forename: John M
authors.initials: JM
authors.lastname: Hutson
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry; D003456:Cryptorchidism / Q000503:physiopathology; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D047629:Estrogen Receptor beta / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005267:Femoral Nerve / Q000502:physiology; D005485:Flutamide / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005865:Gestational Age; D050152:Intra-Abdominal Fat / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development / Q000294:innervation / Q000378:metabolism; D008022:Ligaments / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D008297:Male; D008321:Mammary Glands, Animal / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D012611:Scrotum / Q000196:embryology / Q000254:growth & development; D013737:Testis / Q000196:embryology* / Q000254:growth & development; D013739:Testosterone / Q000502:physiology
chemical_list: D000726:Androgen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011944:Receptors, Androgen; D013739:Testosterone; D005485:Flutamide