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Effects of gonadal steroids on galanin and other neuropeptides in the rat brain
Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 2001. , 64 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 673
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-25705Local ID: 10081ISBN: 91-7219-973-3 (print)OAI: oai:DiVA.org:liu-25705DiVA: diva2:246253
Public defence
2001-05-17, Elsa Brändströms sal, Hälsouniversitetet, Linköping, 09:00
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-06Bibliographically approved
List of papers
1. Radioimmunoassay for rat galanin: immunochemical and chromatographic characterization of immunoreactivity in tissue extracts
Open this publication in new window or tab >>Radioimmunoassay for rat galanin: immunochemical and chromatographic characterization of immunoreactivity in tissue extracts
2000 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 60, no 5, 411-418 p.Article in journal (Refereed) Published
Abstract [en]

Galanin is a regulatory peptide with wide distribution in the central and peripheral nervous system and with numerous biological effects. Several radioimmunoassays based on antisera raised against porcine galanin have been used to measure immunoreactivity in rat tissues. However, considerable lack of parallelism has been observed between the porcine standard and rat tissue extracts, which may decrease the reliability of the quantitative data. The purpose of the present study was therefore to raise antibodies against rat galanin and establish a competitive radioimmunoassay for rat galanin. Two antisera, RatGal4 and RatGal5, were characterized in detail. The homogeneity of the immunoreactive material from several tissues was also investigated with column chromatography. At reverse-phase high-pressure liquid chromatography more than 95% of the immunoreactive material from rat CNS eluted as a single peak in the position of synthetic rat galanin, whereas almost half of the immunoreactive material from the intestine eluted in positions different from the synthetic peptide. Extracts of rat brains as well as jejunum diluted in parallel with the standard curve for both antisera. We conclude that measurements of rat galanin based on these antisera are therefore more reliable than those based on antisera raised against porcine galanin.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25424 (URN)10.1080/003655100750019323 (DOI)9869 (Local ID)9869 (Archive number)9869 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
2. Sex differences in neuropeptide distribution in the rat brain
Open this publication in new window or tab >>Sex differences in neuropeptide distribution in the rat brain
Show others...
1999 (English)In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 20, no 1, 81-86 p.Article in journal (Refereed) Published
Abstract [en]

We have investigated possible sex differences in the regional concentrations of neuropeptides in the rat brain. Immunoreactive neurotensin (NT), neurokinin A (NKA), galanin (GAL), calcitonin gene-related peptide (CGRP), substance P (SP) and neuropeptide Y (NPY) were measured by radioimmunoassay in frontal cortex, occipital cortex, hippocampus, striatum, hypothalamus and pituitary in male and female pre- and postpubertal rats. Sex differences were found for NPY (p < 0.001), NT (p < 0.01) and GAL (p < 0.05), in particular in hippocampus, striatum, hypothalamus and pituitary, but not for CGRP, SP and NKA. Results from analysis of neuropeptides in one sex may not be entirely applicable to the other.

Keyword
Sex differences, Neuropeptide Y, Neurotensin, Galanin, Hippocampus, Pituitary, Frontal cortex, Puberty
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13441 (URN)10.1016/S0196-9781(98)00139-9 (DOI)
Available from: 2005-11-11 Created: 2005-11-11 Last updated: 2017-12-13Bibliographically approved
3. Effects of estradiol, progesterone, and norethisterone on regional concentrations of galanin in the rat brain
Open this publication in new window or tab >>Effects of estradiol, progesterone, and norethisterone on regional concentrations of galanin in the rat brain
1999 (English)In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 20, no 6, 743-748 p.Article in journal (Refereed) Published
Abstract [en]

Concentrations of immunoreactive galanin were compared in eight gross brain regions of ovariectomized female rats treated with either estradiol, estradiol + progesterone, estradiol + norethisterone, or placebo. Higher concentrations with estradiol treatment compared with placebo were found in the pituitary (357%), frontal cortex (162%), occipital cortex (174%), hippocampus (170%), and median eminence (202%). A more profound difference with addition of progesterone or norethisterone was seen in the pituitary (529% and 467%, respectively). Sex steroids, particularly estradiol, modulate galanin concentrations not only in reproductive, but also in nonreproductive, brain regions.

Keyword
Galanin, Estradiol, Progesterone, Norethisterone, Hippocampus, Pituitary, Frontal cortex
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13442 (URN)10.1016/S0196-9781(99)00057-1 (DOI)
Available from: 2005-11-11 Created: 2005-11-11 Last updated: 2017-12-13Bibliographically approved
4. Estradiol causes dose-dependent increase in galanin-like immunoreactivity in both ventral and dorsal hippocampus
Open this publication in new window or tab >>Estradiol causes dose-dependent increase in galanin-like immunoreactivity in both ventral and dorsal hippocampus
(English)Manuscript (preprint) (Other academic)
Abstract [en]

The purpose of the study was to investigate the dose- and duration effects of estradiol treatment on galanin-like immunoreactivity in ventral and dorsal rat hippocampus. Ovariectomized rats were treated three, 20 or 60 days with low or high pharmacological doses of estradiol or with carrier only. Galanin-like immunoreactivity was measured with radioimmunoassay using antiserum GalRat4 raised against rat galanin. ANOVA revealed a significant effect from dose (p<0.001) and from duration (p<0.001) of estrogen treatment, but not from region, i.e. ventral or dorsal hippocampus. With the high pharmacological dose, galanin-like immunoreactivity increased more than 10-fold in comparison with the vehicle-treated in dorsal hippocampus and about 6-fold in ventral hippocampus. The increment is most likely due to an effect in the noradrenergic galanin-expressing neurons originating in locus ceruleus. The functional interpretation of these results is dependent on the yet unknown role of galanin in their hippocampal nerve terminals.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81076 (URN)
Available from: 2012-09-06 Created: 2012-09-06 Last updated: 2012-09-06Bibliographically approved
5. Progesterone and norethisterone have different effects on tachykinin-like immunoreactivity in rat cortex and striatum
Open this publication in new window or tab >>Progesterone and norethisterone have different effects on tachykinin-like immunoreactivity in rat cortex and striatum
2001 (English)In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 101, no 1-3, 87-91 p.Article in journal (Refereed) Published
Abstract [en]

Objective: The purpose of this study was to investigate the effects of progesterone and the most commonly prescribed synthetic progestogen, norethisterone, on regional immune-like reactivity of neuropeptide Y (NPY), substance P (SP), neurokinin A (NKA) and neurotensin (NT) in brains of female ovariectomized estradiol-substituted rats.

Results: Norethisterone+estradiol-treated rats had 44% lower SP levels compared with estradiol-only-treated in frontal cortex and 20% lower NKA levels in comparison with progesterone+estradiol-treated in frontal cortex. Progesterone+estradiol-treated rats had 66% lower SP levels in striatum in comparison with both estradiol-only-treated and norethisterone+estradiol-treated. No significant results were found for NPY and NT.

Conclusion: Progesterone and the synthetic progestogen, norethisterone, have different effects on SP- and NKA-like immunoreactivity in rat cortex and striatum.

The effects of NET on SP- and NKA-like immunoreactivity in frontal cortex may contribute to the mood effects ascribed to this progestogen in clinical usage.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25336 (URN)10.1016/S0167-0115(01)00265-8 (DOI)9778 (Local ID)9778 (Archive number)9778 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved

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