Biomedical subjects
Rauni Saaristo
Publications and source records attributed to Rauni Saaristo.
An in vitro long-term culture model for normal human mammary gland: expression and regulation of steroid receptors.
Steroids and their nuclear receptors play crucial roles in the development and maintenance of normal functions of the human mammary gland (HMG). They have also been implicated in breast carcinogenesis. However, the study of steroid action in normal HMG has been hampered by experimental difficulties. By using a newly established in vitro long-term culture method, we successfully cultured normal HMG tissue for more than 2 months without detriment to its morphology or steroid receptor expression. Expression of the cellular structural and extracellular matrix proteins was similar to that prior to culture, and HMG tissue retained its properties of steroid receptor expression and regulation. Addition of 17-beta estrogen to mammary tissues markedly increased the expression of progesterone receptor (PR) but only slightly affected that of the estrogen receptor (ER). Medroxyprogesterone acetate down-regulated the expression of PR within 24-48 h and also increased the expression of androgen receptor. When HMG tissue was cultured in medium containing normal or dextran-coated charcoal-stripped fetal calf serum or normal human serum, the expression and regulation of steroid hormone receptors were similar, although different in extent. When serum was omitted, the morphology of HMG was normal after 1 week, but the expression and regulation of ER and PR were altered. Thus, as HMGs retain the capacity to express steroid receptors in culture, this long-term culture system is probably a good model for studying the regulation of the mammary gland by steroids.
Is bile flow reduced in patients with hypothyroidism?
BACKGROUND: Disturbances in the sphincter of Oddi (SO) function may prevent normal bile flow and thus enhance the probability of common bile duct stone (CBDS) formation. We have previously shown increased prevalence of diagnosed hypothyroidism in CBDS patients, thyroxine (T(4)) -induced inhibition of the SO contractility both in animal and in human experiments ex vivo, and reduced bile flow to duodenum in hypothyroid rats. The aim of the present study was to investigate human biliary dynamics in relation to altered thyroid gland function. METHODS: Eight female patients, 1 with diagnosed untreated hypothyroidism and 7 with total thyroidectomy performed due to thyroid cancer, were studied in hypothyroid stage and again after thyroxine replacement therapy in euthyroid stage, with quantitative (99m)Tc HIDA cholescintigraphy (QC), biliary ultrasonography, and serum determinations. Each patient served as her own control in the 2 stages of the study. RESULTS: In QC, maximal uptake of (99m)Tc HIDA was not changed in hypothyroidism compared to euthyroidism. The first appearance of radioactivity to large bile ducts at the hepatic hilum remained unchanged in the 2 stages of the study. Hepatic clearance of (99m)Tc HIDA was decreased at 45 minutes (28% [11-38] vs 50% [33-54]; P =.028; median and range) and at 60 minutes (55% [28-80] vs 69% [61-79]; P =.028; median and range) and hilum-duodenal transit time increased by 31% compared to euthyroid stage. In US no changes were seen in gall bladder or bile ducts in the 2 stages of the study. Serum hypercholesterolemia was observed in the hypothyroid stage. CONCLUSIONS: We conclude that hypothyroidism may result in delayed emptying of the biliary tract, as studied with QC. In addition to the changes in bile composition and excretion rate suggested before to take place in hypothyroidism, according to the present study changes in biliary emptying also may be included in the probable causes for the increased prevalence of CBDS in hypothyroidism. This may be due to the absence of the prorelaxing effect of thyroxine on SO, which we have shown before to exist ex vivo.