Endocrine Abstracts (2008) 16 S20.2

SF-1 knockout mice as a model for hormone independent brain sexual differentiation

Tanja Spanic1, Tomaz Budefeld1, Neza Grgurevic1, Stuart Tobet2 & Gregor Majdic1


1University of Ljubljana, Ljubljana, Slovenia; 2Colorado State University, Fort Collins, Colorado, USA.


Animals that are not exposed to endogenous sex steroids during development provide an important model for studying hormone independent development of brain sex differences. Due to gonadal agenesis, male and female steroidogenic factor 1 knockout (SF-1 KO) mice are born phenotypically female. Normally, they die shortly after birth due to adrenal insufficiency. Early corticosteroid injections followed by adrenal transplantation can maintain SF-1 KO mice into adulthood. As several aspects of hypothalamic structure and function do not become apparent until after puberty, examination of brains from adult SF-1 KO mice can provide unique information.

Vasopressin (AVP) neurons in the bed nucleus of the stria terminalis (BNST) show sex differences, with males having more cells and a denser projection to the lateral septum than females. This sex difference was reported as partially hormone independent with a contribution from the presence of sex chromosomes. In the present study, we examined AVP immunoreactive fibers in the lateral septum in SF-1 KO mice to further clarify the extent to which the sex difference is hormone independent or influenced by developmental exposure to sex steroid hormones. After two weeks of treatment with testosterone prior to sacrifice, AVP immunoreactive fibers in the lateral septum of SF-1 KO and prepubertally gonadectomized WT control mice were less than expected, suggesting that exposure to sex steroids over a long period is necessary to maintain normal adult levels of AVP expression in the BNST to lateral septum projection. Statistical analyses did not reveal sex differences in AVP immunoreactive fiber density; however, there were significantly fewer AVP immunoreactive fibers in male SF-1 KO mice, suggesting that exposure to testosterone during the perinatal period is at least partially responsible for the greater AVP expression in WT male mice.

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