The effect of flutamide on expression of androgen and estrogen receptors in the gubernaculum and surrounding structures during testicular descent

J Pediatr Surg. 2011 Dec;46(12):2358-62. doi: 10.1016/j.jpedsurg.2011.09.026.

Abstract

Background/purpose: 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.

Publication types

  • Comparative Study

MeSH terms

  • Androgen Antagonists / pharmacology*
  • Animals
  • Cell Nucleus / chemistry
  • Cryptorchidism / physiopathology
  • Estrogen Receptor alpha / biosynthesis
  • Estrogen Receptor alpha / drug effects*
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor beta / biosynthesis
  • Estrogen Receptor beta / drug effects*
  • Estrogen Receptor beta / genetics
  • Female
  • Femoral Nerve / physiology
  • Flutamide / pharmacology*
  • Gene Expression Regulation, Developmental / drug effects
  • Gestational Age
  • Intra-Abdominal Fat / drug effects*
  • Intra-Abdominal Fat / embryology
  • Intra-Abdominal Fat / growth & development
  • Intra-Abdominal Fat / innervation
  • Intra-Abdominal Fat / metabolism
  • Ligaments / drug effects*
  • Ligaments / embryology
  • Ligaments / growth & development
  • Ligaments / metabolism
  • Male
  • Mammary Glands, Animal / embryology
  • Mammary Glands, Animal / growth & development
  • Mammary Glands, Animal / metabolism
  • Pregnancy
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Androgen / biosynthesis
  • Receptors, Androgen / drug effects*
  • Receptors, Androgen / genetics
  • Scrotum / embryology
  • Scrotum / growth & development
  • Testis / embryology*
  • Testis / growth & development
  • Testosterone / physiology

Substances

  • Androgen Antagonists
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Receptors, Androgen
  • Testosterone
  • Flutamide