ABSTRACT
I. Steroids Differentiate the Brain during a Perinatal Sensitive Period .......................................................................... 320
II. GABA is an Amino Acid Transmitter Expressed Early in Development
.......................................................... 320
III. There are Sex Differences in the GABA System during the Perinatal Sensitive Period ....................................... 321
IV. Reducing GABA Synthesis during the Perinatal Sensitive Period Prevents Normal Masculinization................. 322
V. There is a Developmental Switch in GABA Action from Excitatory to Inhibitory..................................................... 323
VI. Estradiol Lengthens the Duration and Enhances the Magnitude of Excitatory GABA .......................................... 325
VII. Influx of External Calcium is a Regulator of Growth Processes ........................................................................ 327
VIII. Calcium Binding Protein Levels are Higher in Males during the Perinatal Sensitive Period ....................................... 328
IX. Estradiol Aromatized from Testicular Testosterone Increases Calbindin in Males ..................................................... 330
X. There are Sex Differences in the Level of pCREB during the Perinatal Sensitive Period ....................................... 330
XI. Excitatory GABA Increases Phosphorylation of CREB in Males and Inhibitory GABA Decreases Phosphorylation of CREB in Females ....................................... 333
XII. Excitatory GABA is a Major Divergence Point in the Process of Sexual Differentiation............................................... 335
References ............................................................................................. 337
The perinatal period is distinguished by heightened sensitivity of the bipotential brain to gonadal steroid-mediated differentiation. As a result of dimorphic hormone exposure, adult animals exhibit sex-typic behavior, physiology, and brain morphology. Steroid hormones are powerful agents that alter gene expression to influence parameters such as cell growth, differentiation, and death in a variety of tissues, including the brain. These effects are generally manifest as a result of action via steroid receptors, which are members of a transcription factor superfamily. Steroids influence the brain throughout the life span of mammals, but in the rat there is a developmental window beginning in the last week of gestation and terminating a few days after birth during which high levels of estradiol (E
), aromatized from testicularly derived testosterone, masculinize the male brain. Steroidmediated effects during this sensitive perinatal period include alterations in the density of dendritic spines, frequency of neuronal branching, rates of cell death, and degree of myelination.
