| 1. |
- Damberg, Mattias, et al.
(author)
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Investigation of transcription factor AP-2 beta genotype in women with premenstrual dysphoric disorder.
- 2005
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In: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 377:1, s. 49-52
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Journal article (peer-reviewed)abstract
- It has repeatedly been shown that the serotonergic system is involved in the symptomatology of premenstrual dysphoric disorder (PMDD). Women with PMDD are reported to differ from symptom-free controls with regard to serotonin-related biological markers. Evidence from family and twin studies suggests a genetic contribution to the aetiology of PMDD. The expression of human transcription factor AP-2beta in neural crest cell lineages and neuroectodermal cells suggests that this protein may be of importance for functional characteristics of neurons by regulating the expression of target genes. Within the monoaminergic systems, several genes have binding sites for AP-2beta in regulatory regions, suggesting an involvement of AP-2beta in these systems. The gene encoding AP-2beta is located on chromosome 6p12-p21.1 and includes a polymorphic region consisting of a variable number of [CAAA] repeats located in the second intron. We have earlier shown that AP-2beta genotype is associated with serotonergic phenotypes and that brainstem levels of AP-2beta correlate positively to serotonin metabolism in rat frontal cortex. The aim of this study was to investigate the relationship between PMDD and transcription factor AP-2beta genotype. The participants included 176 women with PMDD and 91 healthy controls. Genotyping was performed by polymerase chain reactions. We did not observe any differences in AP-2beta genotype frequencies between PMDD subjects and controls. Our results suggest that AP-2beta genotype is not a risk factor for PMDD. To our knowledge, this is the first study investigating transcription factor AP-2beta genotype in women with PMDD. Hence, these results should be considered preliminary until replicated.
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| 2. |
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| 3. |
- Eriksson, Olle, et al.
(author)
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Mood changes correlate to changes in brain serotonin precursor trapping in women with premenstrual dysphoria.
- 2006
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In: Psychiatry research. - : Elsevier BV. - 0165-1781 .- 0925-4927 .- 1872-7506. ; 146:2, s. 107-16
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Journal article (peer-reviewed)abstract
- The cardinal mood symptoms of premenstrual dysphoria can be effectively treated by serotonin-augmenting drugs. The aim of the study was to test the serotonin hypothesis of this disorder, i.e. of an association between premenstrual decline in brain serotonin function and concomitant worsening of self-rated cardinal mood symptoms. Positron emission tomography was used to assess changes in brain trapping of 11C-labeled 5-hydroxytryptophan, the immediate precursor of serotonin, in the follicular and premenstrual phases of the menstrual cycle in eight women with premenstrual dysphoria. Changes in mood and physical symptoms were assessed from daily visual analog scale ratings. Worsening of cardinal mood symptoms showed significant inverse associations with changes in brain serotonin precursor trapping; for the symptom "irritable", r(s)=-0.83, and for "depressed mood" r(s)=-0.81. Positive mood variables showed positive associations, whereas physical symptoms generally displayed weak or no associations. The data indicate strong inverse associations between worsening of cardinal symptoms of premenstrual dysphoria and brain serotonin precursor (11C-labeled 5-hydroxytryptophan) trapping. The results may in part support a role for serotonin in premenstrual dysphoria and may provide a clue to the effectiveness of serotonin-augmenting drugs in this disorder but should, due to small sample size and methodological shortcomings, be considered preliminary.
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| 4. |
- Eriksson, Olle, 1954-
(author)
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Studies on Premenstrual Dysphoria
- 2005
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Doctoral thesis (other academic/artistic)abstract
- Premenstrual dysphoria, so severe that it affects the lives of the women afflicted, is the condition studied in this thesis. Physiological and pharmacological mechanisms of pathogenetic relevance were investigated. Women with premenstrual dysphoria showed a stronger and less dampened response of LH to an estradiol challenge than asymptomatic women, indicating an altered neuroendocrine regulation. In women with premenstrual dysphoria, the LH response was correlated to the severity of irritability and bloating, and the early FSH response was correlated to the severity of depressed mood. The positron-emission study showed strong, consistent correlations between worsening of mood symptoms and a decrease in brain trapping of the immediate serotonin precursor, from the mid-follicular to the late luteal phase in women with premenstrual dysphoria. The strongest correlations were seen for the cardinal mood symptoms of premenstrual dysphoria, and for their opposites. Physical symptoms showed weaker or no correlations with the exception of nociceptive symptoms from erogenous body regions which showed positive correlations to serotonin precursor trapping in the right caudate nucleus. The findings are consistent with the serotonin hypothesis of premenstrual dysphoria, and might possibly explain the observed effects of serotonin-augmenting drugs in this condition.The partial 5-HT1A receptor agonist buspirone was superior to placebo in the treatment of premenstrual dysphoria. The weak SRI and 5-HT2 receptor antagonist nefazodone was not superior to placebo. For women with premenstrual dysphoria in need of medication and who do not tolerate SRIs because of the sexual sideeffects, buspirone may be an alternative drug, since it had no adverse effects on sexual function. The prevalence of polycystic ovaries and serum levels of androgens were not higher in women with premenstrual dysphoria than in their asymptomatic counterparts. The findings are not consistent with the hypothesis that irritability in women with premenstrual dysphoria is induced by elevated testosterone levels. Thesis results, which are in line with the serotonin hypothesis of premenstrual dysphoria, may imply that increased brain sensitivity is one of the factors underlying severe premenstrual mood symptoms, thereby further supporting a common serotonergic dysregulation in this condition.
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| 5. |
- Hallberg, Gunilla, et al.
(author)
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Effects of pre-and postmenopausal use of exogenous hormones on receptor content in normal human breast tissue: A randomized study
- 2008
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In: Gynecological Endocrinology. - : Informa UK Limited. - 0951-3590 .- 1473-0766. ; 24:8, s. 475-480
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Journal article (peer-reviewed)abstract
- Objective. To examine the effects of exposure to endogenous and exogenous hormones on estrogen receptor- (ER) and progesterone receptor (PR) levels in normal human breast tissue. Methods. In a randomized study of women scheduled for mammary reduction plasty (n = 81), ER and PR content in breast parenchyma was analyzed in premenopausal (n = 49) and postmenopausal (n = 16) women. Premenopausal women were randomized to surgery in the follicular or luteal phase of the menstrual cycle or after oral contraceptive treatment for 2 months. Postmenopausal women were randomized to sequential or estrogen-only therapy for 2 months prior to surgery. Results. ER content was higher in parous than in nulliparous (p = 0.009) premenopausal women and displayed a positive association with age (rs = 0.51, p = 0.0002). Compared with premenopausal women in the follicular phase, postmenopausal women had higher ER content (p = 0.040) whereas premenopausal women on oral contraception had lower ER (p = 0.048) and PR (p = 0.007) content. Smokers had lower PR content than non-smokers (p = 0.02). Conclusion. In the present study ER content was higher in parous than in non-parous women and associated with premenopausal age. Short-term oral contraceptives yielded lower ER and PR contents. Postmenopausal estrogen/progestogen combined therapy yielded lower PR content than estrogen-only therapy.
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| 6. |
- Hanrieder, Jörg, 1980, et al.
(author)
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Proteomic analysis of human follicular fluid using an alternative bottom-up approach.
- 2008
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In: Journal of proteome research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 7:1, s. 443-9
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Journal article (peer-reviewed)abstract
- Human follicular fluid (hFF) is the in vivo environment of oocytes during follicular maturation in the ovaries. It contains a huge variety of compounds such as, e.g., proteins that might play an important role in follicular development and oocyte growth. Previous proteomic studies on follicular fluid have isolated and already identified a certain number of proteins. Nevertheless, only a small part of proteins present in follicular fluid have been covered so far and a large number have still not been identified. Therefore, the need for new, more resolving, and sensitive approaches in proteome research is evident. We utilized a proteomic setup based on in solution isoelectric focusing (IEF) and reversed-phase nanoliquid chromatography coupled to matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (nano-LC MALDI TOF/TOF MS) for in depth protein analysis of human follicular fluid samples of patients undergoing controlled ovarian hyper stimulation (COH) for in vitro fertilization therapy (IVF). This approach led to the significant identification of 69 proteins, where 32 have not been reported before to be found in human follicular fluid with proteomic methods. Among these findings, at least two relevant compounds essentially involved in hormone secretion regulation during the folliculogenetic process were identified: sex hormone binding globulin (SHBG) and inhibin A (INHA). To confirm these results, both proteins were further validated by immunoassays.
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| 7. |
- Kirilovas, Dmitrijus, et al.
(author)
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Conversion of circulating estrone sulfate to 17β-estradiol by ovarian tumor tissue : A possible mechanism behind elevated circulating concentrations of 17β-estradiol in postmenopausal women with ovarian tumors
- 2007
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In: Gynecological Endocrinology. - : Informa UK Limited. - 0951-3590 .- 1473-0766. ; 23:1, s. 25-28
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Journal article (peer-reviewed)abstract
- AIM: Elevated serum levels of 17beta-estradiol (E2) are frequently found in postmenopausal women with ovarian tumors not classified as estrogen-producing. Conversion of circulating estrone sulfate (E1S) to E2 is one alternative way of E2 formation in target tissues in postmenopausal women. Our aim was to find out if conversion of circulating E1S to E2 by the tumor tissue could be a reason for elevated serum E2 levels in postmenopausal women with 'non-estrogen-producing' ovarian tumors. METHOD: Serum E2 was measured in 12 postmenopausal women with 'non-estrogen-producing' ovarian tumors (nine benign, three malignant). Total hydrolysis of and [3H]E2 formation from [3H]E1S by the tumor tissue homogenates was studied in vitro. RESULTS: Serum E2 showed significant positive correlations with total hydrolysis of and [3H]E2 formation from [3H]E1S in the total material as well as in the benign tumor subgroup. [3H]E2 formation was the most important independent variable. CONCLUSION: Conversion of circulating E1S to E2 by the tumor tissue could be one important reason for elevated S-E2 levels in postmenopausal women with 'non-estrogen-producing' ovarian tumors.
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| 8. |
- Kirilovas, Dmitrijus, et al.
(author)
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Granulosa cell aromatase enzyme activity : Effects of follicular fluid from patients with polycystic ovary syndrome, using aromatase conversion and [11C]vorozole-binding assays
- 2006
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In: Gynecological Endocrinology. - : Informa UK Limited. - 0951-3590 .- 1473-0766. ; 22:12, s. 685-691
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Journal article (peer-reviewed)abstract
- The local regulation of ovarian aromatase enzyme in polycystic ovary syndrome (PCOS) was studied with aromatase conversion and [C-11]vorozole-binding assays to analyze aromatase activity, substrate-enzyme affinity and number of aromatase binding sites in non-cultured human granulosa cells (GC) incubated with different sources and preparations of follicular fluid (FF). Incubation with FF from women stimulated in in vitro fertilization cycles with follicle-stimulating hormone yielded higher conversion activity than with FF from healthy women and PCOS patients, paralleled with higher substrate affinity (lower K-d) than with FF from healthy women. In PCOS women, charcoal-pretreated FF yielded higher conversion, whereas the ether-pretreated FF yielded lower conversion activity, than with untreated PCOS FF. Both preparations of FF yielded higher affinity to substrate (lower Kd values) and the ether-pretreated FF a lower number of binding sites (B-max). It seems that steroids with the presence of proteins in PCOS FF reduced aromatase conversion activity through decreased substrate affinity, whereas FF preparations devoid of proteins reduced the aromatase conversion activity mainly through blocking of aromatase active sites. Identification of specific agents responsible for this rapid regulation of aromatase function might help to understand normal regulation of the menstrual cycle and supposed imbalances of inhibitors/activators in PCOS.
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| 9. |
- Kristjánsdóttir, Jóna, et al.
(author)
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Health-related self-assessed quality of life in young people at a Youth Centre in Sweden
- 2009
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In: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 23:3, s. 465-472
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Journal article (peer-reviewed)abstract
- Objective: To study the self-reported health of young people visiting a Youth Centre (YC) at a University hospital, describe possible gender differences and to compare the results with those in previous Swedish reports on similar age groups using the same instrument. Design: All young people who visited a YC at a particular, randomly chosen time, were verbally asked to fill out a questionnaire, Short Form 36. The interviews were conducted during a 12-month period to lessen the impact of seasonal variations. Setting: A YC at the department for obstetrics and gynaecology, Uppsala University hospital. Participants: A total of 1495 young people aged 14-25 years who visited the YC. Results: The study population (n = 1495). Response rate was 96%. This population reported lower overall scores compared with the normative Swedish population from 1992. Further, females scored significantly lower than males on all subscales (p < 0.001), except for 'Physical Functioning'. The lowest scores were reported for the subscales Vitality, Role Emotional and Mental Health. Conclusion: This study describes physical functioning and mental health among young people visiting a YC. The results indicate a worsening of the perceived physical and MH in young individuals, especially in young women. Further studies are needed to monitor changes in MH and quality of life over time in this group and assess the effects of interventions. This study enhances the importance of a holistic approach towards health and health promotion comprising both physical and mental health issues.
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| 10. |
- Kushnir, Mark M, et al.
(author)
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Steroid profiles in ovarian follicular fluid from regularly menstruating women and women after ovarian stimulation
- 2009
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In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 55:3, s. 519-526
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Journal article (peer-reviewed)abstract
- BACKGROUND: Information on the concentrations of steroids in ovarian follicular fluid (FF) from regularly menstruating (RM) women has been limited because of the absence of methods for the simultaneous quantification of multiple steroids in small volumes of FF. We studied steroid profiles in FF during the early follicular phase of the menstrual cycle and after ovarian stimulation for in vitro fertilization (IVF), and compared concentrations with published values obtained by immunoassay (IA). METHODS: We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure 13 steroids in 40-microL aliquots of FF samples from 21 RM women and from 5 women after ovarian stimulation for IVF. Relationships between concentrations of steroids and their ratios (representations of the enzyme activities) were evaluated within and between subgroups. RESULTS: The concentrations of testosterone (Te), androstenedione (A4), and estradiol (E2) measured by LC-MS/MS were lower than those previously reported in studies with IAs. In RM women, androgens were the most abundant class of steroids, with A4 being the major constituent. The concentrations of 17-hydroxyprogesterone (17OHP), total androgens, and estrogens were 200- to 1000-fold greater in FF than in serum. Compared with RM women, FF samples from women undergoing ovarian stimulation had significantly higher concentrations of E2 (P = 0.021), pregnenolone (P = 0.0022), 17OHP (P = 0.0007), and cortisol (F) (P = 0.0016), and significantly higher ratios of F to cortisone (P = 0.0006), E2 to estrone (P = 0.0008), and E2 to Te (P = 0.0013). CONCLUSIONS: The data provide the first MS-based concentration values for 13 steroids in ovarian FF from RM women, from estrogen- and androgen-dominant follicles, and from women after ovarian stimulation for IVF.
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