Sex differences in brain and plasma beta-endorphin content following testosterone, dihydrotestosterone and estradiol administration to gonadectomized rats

Neuroendocrinology. 2009;89(4):411-23. doi: 10.1159/000209506. Epub 2009 Mar 19.


Aims: The present study aims at evaluating the effect of a 2-week treatment with testosterone (T), dihydrotestosterone (DHT) and estradiol valerate (E(2)V) on brain and plasma beta-endorphin (beta-END) concentrations in gonadectomized rats of both sexes.

Methods: Eight groups of female and 8 groups of male Wistar rats were included. For each sex, 1 group of gonad-intact and 1 group of gonadectomized rats were employed as controls (placebo). The other groups received subcutaneous T at the doses of 10 and 100 microg/kg/day (female rats) or 1 and 5 mg/kg/day (male rats). Subcutaneous DHT was administered at the doses of 1, 10, 100 microg/kg/day (female rats) or 0.1, 1 and 5 mg/kg/day (male rats). E(2)V was administered subcutaneously at 0.05 mg/kg/day. beta-END levels were measured in different brain areas and plasma.

Results: Ovariectomy (OVX) induced a significant decrease in beta-END in all brain areas analyzed as well as in plasma. Orchidectomy (OCX) reduced opioid concentration in the hypothalamus, anterior pituitary and neurointermediate lobe. In OVX rats, T replacement as well as E(2)V significantly increased beta-END concentration in all brain areas and in plasma. In the OCX group, T and E(2)V did not influence beta-END concentrations in different hypothalamic areas. However, they produced a significant rise in beta-END levels in the hypothalamus, neurointermediate lobe, anterior pituitary and plasma. Conversely, DHT replacement did not affect beta-END levels at any dose administered, either in males or females.

Conclusions: The sensitivity of the endogenous opiatergic system to T administration seems to be sex-related. This effect is particularly evident in the brains of female animals where this endogenous endorphin elicits a much greater response than it does in males that have undergone gonadal steroid depletion and subsequent T replacement.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Dihydrotestosterone / administration & dosage*
  • Estradiol / administration & dosage*
  • Female
  • Male
  • Orchiectomy
  • Ovariectomy
  • Rats
  • Rats, Wistar
  • Sex Characteristics*
  • Testosterone / administration & dosage*
  • beta-Endorphin / blood
  • beta-Endorphin / metabolism*


  • Dihydrotestosterone
  • Testosterone
  • Estradiol
  • beta-Endorphin