Many women experience mental or emotional changes when variations occur in the plasma concentrations of their ovarian hormones. These observations are supported by a large number of scientific reports concerning interactions between ovarian steroids and cerebral functions, e.g. mood, cognition and motor function. Activation of genes is a fundamental principle by which steroids exert effects in neurons, thereby regulating the expression of enzymes, receptor proteins, trophic factors and regulatory peptides. This thesis examines the hypothesis that sex steroid hormones can modify concentrations of peptides important for neuronal transmission in brain areas relevant for the above-mentioned modalities. A necessary starting point in this quest is to develop good quantitative data on neuropeptide concentrations in relation to sex steroid status. Accordingly, the general aim of the thesis is to investigate the influence of gender and sex steroid exposure on neuropeptide concentrations and identify one or several steroid-sensitive neuropeptides in extrahypothalamic brain regions of the rat.
Neuropeptide concentrations were measured with radioimmunoassay in extracts of extrahypothalarnic brain regions. A new radioimmunoassay, specific for rat galanin, was developed. Concentrations of neuropeptides were compared between sexes, across puberty and in ovariectomized animals treated with different doses and durations of estradiol, progesterone and norethisterone.
We found that differences in sex steroid exposure between gender, across puberty, and duting exogenous treatment correlate with differences in concentrations of neuropeptide immunoreactivities in several extrahypothalarnic regions of the rat brain. In particular galanin in rat hippocampus is sensitive to estrogen and can be increased in a dose-dependent manner with chronic estradiol treatment. It is likely that the increase mainly sterns from the ascending noradrenergic neuron system originating in locus cemleus. Chromatographic characterization shows that galanin, measured by the antisera Ga1Rat4 and Ga1Rat5, has a high degree of homogeneity in rat brain tissue. Norethisterone and progesterone have different effects on substance P and neuroldnin A in rat frontal cortex and striatum.
These findings could contribute to the understanding of how mood and cognition are affected by sex steroids in females and how estradiol interacts with neurons affected by Alzheimer's disease.
Linköping: Linköpings universitet , 2001. , 64 p.