Organizational effects of testosterone, estradiol, and dihydrotestosterone on vasopressin mRNA expression in the bed nucleus of the stria terminalis

J Neurobiol. 2003 Feb 15;54(3):502-10. doi: 10.1002/neu.10157.


In adulthood, male rats express higher levels of arginine vasopressin (AVP) mRNA in the bed nucleus of the stria terminalis (BST) than do female rats. We tested whether this sex difference is primarily due to differences in neonatal levels of testosterone. Male and female rats were gonadectomized on the day of birth and treated with testosterone propionate (TP) or vehicle on postnatal days 1, 3, and 5 (P1, P3, and P5). Three months later, all rats were implanted with testosterone-filled capsules. Two weeks later, brains were processed for in situ hybridization to detect AVP mRNA. We found that neonatal TP treatment significantly increased the number of vasopressinergic cells in the BST over control injections. We then sought to determine the effects of testosterone metabolites, estradiol and dihydrotestosterone, given alone or in combination, on AVP expression in the BST. Rat pups were treated as described above, except that instead of testosterone, estradiol benzoate (EB), dihydrotestosterone propionate (DHTP), a combination of EB and DHTP (EB+DHTP), or vehicle was injected neonatally. Neonatal treatment with either EB or EB+DHTP increased the number of vasopressinergic cells in the BST over that of DHTP or oil treatment. However, treatment with DHTP also significantly increased the number of vasopressinergic cells over that of oil treatment. Hence, in addition to bolstering evidence that estradiol is the more potent metabolite of testosterone in causing sexual differentiation of the brain, these data provide the first example of a masculinizing effect of a nonaromatizable androgen on a sexually dimorphic neuropeptide system.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Androgens / pharmacology
  • Animals
  • Animals, Newborn
  • Castration
  • Dihydrotestosterone / pharmacology*
  • Estradiol / pharmacology*
  • Female
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • In Situ Hybridization
  • Male
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Septal Nuclei / cytology
  • Septal Nuclei / drug effects*
  • Septal Nuclei / growth & development
  • Septal Nuclei / metabolism
  • Sex Characteristics
  • Testosterone / pharmacology*
  • Vasopressins / drug effects
  • Vasopressins / genetics
  • Vasopressins / metabolism*


  • Androgens
  • RNA, Messenger
  • Dihydrotestosterone
  • Vasopressins
  • Testosterone
  • Estradiol