| 1. |
- Gebre-Medhin, Maria, 1965
(författare)
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Prolactin and growth hormone in breast cancer. Studies of human breast cancer and transgenic tumor models
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prolactin (PRL) and growth hormone (GH) are two related pituitary peptide hormones of importance during normal mammary gland development. Furthermore, their involvement in development and growth of malignant mammary tumors has been suggested by several investigators. By producing rat PRL transgenic (rPRL) mice and bovine GH transgenic (bGH) mice it was shown that activation of the PRL receptor (PRLR) but not the GH receptor (GHR) is important for mammary tumor development in mice. Mammary explant organ culture studies suggest a functional role of rPRL locally produced in the mammary gland.Studies of rPRL mammary glands with different degrees of hyperplasia showed that the percentage of estrogen receptor a (ERa)-expressing epithelial cells was markedly increased in severely hyperplastic rPRL mammary glands. Plasma levels of 17ß-estradiol, estimated over a 34-day period of time were increased in rPRL mice, while progesterone levels were unchanged compared to control animals. Together these data suggest a role of increased ERa activation during mammary tumor development in rPRL mice. It was also shown that insulin-like growth factor (IGF)-I receptor (IGF-IR) activation is important for rPRL mammary tumor cell growth in vitro, while mRNA expression levels of IGF-I, IGF-II and IGF-IR in rPRL mammary glands do not increase during the course of mammary tumor development.GHR expression was studied in human breast cancer specimens, and it was found that nearly all tumors analyzed expressed GHR. By immunohistochemical studies and by western blot analyses it was found that GHR expression was increased in most tumor tissues compared to adjacent normal mammary tissues.
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| 2. |
- Gustafsson, Jan, et al.
(författare)
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APSI - svår autoimmun sjukdom med endokrina och icke-endokrina symtom
- 2004
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 101:24, s. 2096-2103
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyglandular syndrome type I (APS I) is an autosomal recessive disorder characterized by a combination of autoimmune manifestations affecting endocrine and non-endocrine organs. APS I usually presents in childhood. The three most common manifestations are chronic mucocutaneous candidiasis, hypoparathyroidism and Addison's disease. At least two of these must be present to fulfill the diagnostic criteria of this syndrome. The spectrum of other associated diseases includes gonadal insufficiency, alopecia, vitiligo and chronic active hepatitis. APS I is caused by a mutation in the AIRE-gene (autoimmune regulator) located on chromosome 21. Analysis of specific autoantibodies against intracellular enzymes, particularly enzymes in the synthesis of steroids and neurotransmittors, can be used in the diagnosis of APS I and to predict different manifestations of the disease.
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| 3. |
- Ling, Charlotte, et al.
(författare)
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Prolactin (PRL) receptor gene expression in mouse adipose tissue: increases during lactation and in PRL-transgenic mice
- 2000
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Ingår i: Endocrinology. - 0013-7227 .- 1945-7170. ; 141:10, s. 3564-3572
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Tidskriftsartikel (refereegranskat)abstract
- There are indications that PRL may exert important metabolic actions on adipose tissue in different species. However, with the exception of birds, the receptor has not been identified in white adipose tissue. The present study was designed to examine the possible expression and regulation of the PRL receptor (PRLR) in mouse adipose tissue. The long PRLR messenger RNA (mRNA) splice form (L-PRLR) and two short splice forms (S2- and S3-PRLR) were detected in mouse adipose tissue by RT-PCR. Furthermore, L-PRLR mRNA was detected by ribonuclease protection assay. Immunoreactive PRLR with a relative molecular mass of 95,000 was revealed by immunoblotting. Furthermore, L-PRLR mRNA expression was demonstrated in primary isolated adipocytes. In mouse adipose tissue, the level of L-PRLR mRNA expression increased 2.3-fold during lactation compared with those in virgin and pregnant mice. In contrast, in the liver the expression of L-PRLR increased 3.4-fold during pregnancy compared with those in virgin and lactating mice. When comparing the levels of L-PRLR expression in virgin female and male mice, no difference was detected in adipose tissue. However, in virgin female liver the expression was 4.5-fold higher than that in male liver. As PRL up-regulates its own receptor in some tissues, we analyzed L-PRLR expression in PRL-transgenic female and male mice. In PRL-transgenic mice L-PRLR expression was significantly increased in both adipose tissue (1.4-fold in females and 2.4-fold in males) and liver (1.9-fold in females and 2.7-fold in males) compared with that in control mice. Furthermore, in female PRL-transgenic mice retroperitoneal adipose tissue was decreased in weight compared with that in control mice. However, no difference was detected when comparing the masses of parametrial adipose tissue. Our results suggest a direct role for PRL, mediated by PRLR, in modulating physiological events in adipose tissue.
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| 4. |
- Söderbergh, Annika, et al.
(författare)
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Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I
- 2004
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 89:2, s. 557-562
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of autoantibodies against nine intracellular enzyme autoantigens, namely 21-hydroxylase, side-chain cleavage enzyme (SCC), 17 alpha-hydroxylase, glutamic acid decarboxylase 65, aromatic L-amino acid decarboxylase, tyrosine phosphatase-like protein IA-2, tryptophan hydroxylase (TPH), tyrosine hydroxylase, cytochrome P450 1A2, and against the extracellular calcium-sensing receptor, was assessed in 90 patients with autoimmune polyendocrine syndrome type I. A multivariate logistic regression analysis was performed for the presence of autoantibodies as independent predictors for different disease manifestations. Reactivities against 21-hydroxylase and SCC were associated with Addison's disease with odds ratios (ORs) of 7.8 and 6.8, respectively. Hypogonadism was exclusively associated with autoantibodies against SCC with an OR of 12.5. Autoantibodies against tyrosine phosphatase-like protein IA-2 were associated with insulin-dependent diabetes mellitus with an OR of 14.9, but with low sensitivity. Reactivities against TPH and, surprisingly, glutamic acid decarboxylase 65, were associated with intestinal dysfunction, with ORs of 3.9 and 6.7, respectively. TPH reactivity was the best predictor for autoimmune hepatitis, with an OR of 27.0. Hypoparathyroidism was not associated with reactivity against any of the autoantigens tested. No reactivity against the calcium-sensing receptor was found. Analysis of autoantibodies in autoimmune polyendocrine syndrome type I patients is a useful tool for establishing autoimmune manifestations of the disease as well as providing diagnosis in patients with suspected disease.
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