Thyroid gland is composed of many spheroid structures called thyroid follicles, in which thyrocytes are integrated in their specific structural and functional polarization. In conventional monolayer and floating cultures, the cells cannot reorganize follicle structures with normal polarity. By contrast, in a 3-D collagen gel culture thyrocytes easily and stably reconstruct follicles with physiological polarity. Integration of thyrocyte growth and differentiation appears to result in eventual thyroid folliculogenesis. 3-D collagen gel culture and subacute thyroiditis, a specific thyroid disorder, are the promising models for addressing the mechanism of thyroid folliculogenesis. Because formation of 3-D follicles actively occurs both in this culture system and at the regenerative stage of the disease. The understanding of the mechanistic basis of folliculogenesis is prerequisite for establishment of an artificial thyroid tissue, which would enable a more physiological approach to the treatment of hypothyroidism caused by various diseases and surgical processes than conventional hormone replacement therapy. In this review, we have discussed thyrocyte integration, and thyroid folliculogenesis and tissue regeneration, to further thyroid biology. Also, we briefly discussed a perspective on thyroid tissue regeneration and engineering.
Vitamin D 1α-hydroxylase is a key enzyme for the vitamin D-calcium homeostasis. Recently, 1α-hydroxylase cDNA and gene were cloned. Human 1α-hydroxylase gene is located at chromosome 12q13.3. Several inactivating mutations in the 1α-hydroxylase gene were found in VDDR I patients, and it was established that 1α-hydroxylase gene is responsible for VDDR I. To date, various mutations spreading over all exons have been reported. The cloning of 1α-hydroxylase gene will further lead to the better understanding of vitamin D regulation in both normal and pathological states. In addition, 1α-hydroxylase knock-out mice, which is recently generated, would be a useful model animal for VDDR I [38, 39].
The aim of this experiment was to examine the regulation of p38 mitogen-activated protein (MAP) kinase by platelet-derived growth factor (PDGF)-BB and its biological effects on rat cultured vascular smooth muscle cells (VSMCs). VSMCs were obtained from aortae of male Wistar rats by the media explant technique. After being stimulated by PDGF-BB with or without the p38 MAP kinase-specific inhibitor, SB-203580, the cells were solubilized, and the levels of phosphorylated p38 MAP kinase were examined by immunoblot analysis. The amounts of DNA synthesis and content were measured by using [3H]-thymidine and Hoechst-33258 dye, respectively. The detection of apoptotic cells was evaluated by the TUNEL method. PDGF-BB could phosphorylate p38 MAP kinase dose-dependently, and the phosphorylation was specifically inhibited by SB-203580 in a dose-dependent manner. However, PDGF-BB did not affect the protein level of p38 MAP kinase. Both [3H]-thymidine incorporation and total cellular DNA content were increased by PDGF-BB, and these elevations were prevented by SB-203580. In contrast, PDGF-BB-stimulated VSMCs did not show apoptotic change in spite of the presence or absence of SB-203580. These results established that PDGF-BB activated p38 MAP kinase and subsequently regulated cell growth in VSMCs, providing a molecular mechanism by which p38 MAP kinase can cause the development of cardiovascular diseases, including atherosclerosis.
There is accumulating evidence that interleukin-1 (IL-1) levels are increased locally at the site of active bone resorption in a variety of diseases including osteoporosis, periodontal disease and rheumatoid arthritis. However, the pathogenic role of IL-1 in bone loss remains to be fully elucidated. We present here additional evidence that IL-1β enhances endothelial activation and thereby stimulates mobilization of peripheral blood mononuclear cells (PBMCs) from luminal to abluminal spaces across the endothelium. Furthermore, IL-1β stimulates the differentiation of PBMCs into osteoclast-like cells with bone-resorbing activity in the presence of human osteoblastic SaOS-2 cells without systemic hormones. These findings provide circumstantial evidence for the hypothesis that IL-1β generated in the bone microenviroment plays a stimulatory role in PBMC mobilization from the peripheral circulation and their subsequent differentiation into osteoclast-like cells in the bone tissue. In addition, the present study supports the notion that osteoclast progenitor cells might be derived from the peripheral circulating blood mononuclear cells in human.
We report the kindred with familial isolated hyperparathyroidism with parathyroid cancer. The proband was diagnosed as having primary hyperparathyroidism at age 43. The same disorder was also found in his daughter who had low bone mass. His son was found to have primary hyperparathyroidism by family screening. The pathological diagnosis of the resected parathyroid in both father and daughter was parathyroid cancer, and that in son was parathyroid adenoma. The right lower gland of the proband and the left lower gland of the son were present in thymus. No mutations were found in the sequences of MEN1 gene, hence gene(s) other than MEN1 gene may have contributed to the malignant potency in our cases.
We present a 10-year old boy with central diabetes insipidus (CDI) showing hyperintensity in a normalsized posterior pituitary on magnetic resonance (MR) T1-weighted image (T1WI). He complained of nocturnal enuresis and polyuria. Daily urine volume increased to 4 to 5 L, and AVP plasma level was very low. Polymerase chain reaction (PCR)-amplified exons of the arginine vasopressin (AVP)-neurophysin (NP) II gene were sequenced. Nucleotide-1884 guanine in Exon 2 was substituted with thymine, which induced a substitution of glycine for valine at amino acid position 65 in the NP II moiety. However, MR imaging showed hyperintensity in the posterior pituitary on T1WI. These results suggest that the MR findings of the posterior pituitary in CDI may vary.
We have recently isolated two untranslated first exons, exon ON and exon OS, of rat estrogen receptor alpha (ERα) gene from the liver by use of 5' -rapid amplification of the cDNA ends (5'-RACE) method. In this communication, we further analyzed the 5'-untranslated region (UTR) of the ERα mRNA in rat anterior hypophysis in order to investigate the existence of the other 5'-untranslated exon(s) of rat ERα gene. Total RNA from the anterior hypophysis of 8-week-old female Wistar strain male rats was subjected to 5' -RACE with antisense primers located in exon 1 of the rat ERα gene and one of the positive clones (clone 35) was sequenced. The nucleotide sequence of clone 35 revealed the insertion of a previously unidentified exon (which we termed “exon 0T”) between exon 0 (the first reported 5'-UTR form of rat ERa mRNA) and exon 1 of rat ERα mRNA. Analysis of rat genomic DNA indicated that exon 0T was located between exon 0 and exon 1 of rat ERα gene. We further investigated the distribution of ERα mRNA containing exon 0T in several brain regions and various peripheral tissues of 8-week-old male and female Wistar strain rats by use of reverse transcription-polymerase chain reaction (RT-PCR). The distribution of the ERα mRNA (0T-1) was essentially similar to that of ERα mRNA in which exon 0 was spliced onto exon 1 reported previously. These results indicate that (1) exon 0T is a novel untranslated exon of rat ERα gene which is located between exon 0 and exon 1 on rat genomic DNA, (2) exon 0T is inserted between exon 0 and exon 1 of ERα mRNA by alternative splicing, and (3) this alternative splicing may occur in tissues where the transcription of ERα gene is initiated from exon 0.
The effects of an aqueous extract of Ferula hormonis on social aggression, fertility and some physiological and biochemical parameters were investigated in male mice. The ingestion of 3mg/kg of aqueous extract of F. hormonis for six weeks clearly inhibited social aggression. Body wet weight and other sex accessory organ weights were significantly reduced by this treatment. The ingestion of this extract by male mice resulted in a significant reduction of their fertility. This treatment caused a significant decrease in the number of pregnant females, number of implantations and viable fetuses in females impregnated by males that ingested this extract. Additionally, the numbers of epididymal sperm and their motility were dramatically reduced in F. hormonis-treated mice. Concomitant increases in sperm abnormalities were also observed when compared with control. These data indicate that F. hormonis exposure during this period puts the exposed animals at significant risk for reduced reproductive capacity in adulthood.
A 50-year-old man presented with hypopituitarism and a pituitary lesion on magnetic resonance imaging scan. He was diagnosed as having lymphocytic hypophysitis, and replacement therapy with hydrocortisone and thyroxine was started. He regained normal pituitary function after 10 months. Reports of spontaneous recovery from Lymphocytic hypophysitis in men are rare. While the natural history of lymphocytic hypophysitis remains elusive and its management is not well established, our report shows that spontaneous resolution may occur with steroid supplementation even in men.
In order to examine the relationship between anti-insulin antibodies (AIA) caused by extrinsic human insulin and albuminuria or proteinuria, 53 human insulin-treated type 2 diabetics were divided into two groups: (AIA(+) group) 27 patients with a titer of AIA greater than 7.6% and (AIA(-) group) 26 patients with a titer of AIA less than 7.5%. Although no significant difference was found between the two groups for age, gender, body mass index, duration of diabetes, duration of insulin treatment, blood pressure, serum creatinine, glycosylated hemoglobin (HbAlc), daily dose of insulin, daily insulin injection times, or treatment of hypertension, the AIA(+) group had a significantly higher urinary albumin to creatinine ratio and urinary protein to creatinine ratio than the AIA(-) group (p<0.05). It is suggested that AIA in type 1 diabetics might be insulin autoantibodies, which is not the case with type 2 diabetics. To our knowledge this is the first study demonstrating the relationship between AIA induced not by porcine or bovine insulin, but by human insulin and albuminuria or proteinuria in type 2 diabetics.
A 63-year-old man, who presented with visual field loss due to pituitary tumor, received an intravenous bolus injection of thyrotropin and gonadotropin releasing hormones and insulin as a preoperative evaluation. He complained of severe headache and nausea 2 hours after injection. Emergent CT scan showed no evidence of intratumoral hemorrhage. The next day, his visual field became null. MR images revealed heterogeneous mixed intensity lesions. Under diagnosis of pituitary apoplexy, he underwent transsphenoidal tumor removal 30 hours after onset. Intraoperative and pathological findings showed tumor hemorrhage and adjacent necrotic change. Fourteen cases with sufficient clinical detail in the literature are reviewed: All of the cases had macroadenoma with suprasellar extension. Testing agents were gonadotropin and thyrotropin releasing hormones in 92.9% and 85.7% of cases, respectively. Headache was an initial symptom and started within two hours in all cases but one. Half of the cases showed no change on CT scan. However, tumor hemorrhage was evidenced in 92.9% of cases with or without necrosis due to ischemic change, intraoperatively or pathologically. It is speculated that pituitary apoplexy often starts with infarction possibly due to vasoactive effect of testing agents and later develops into hemorrhage. Therefore, it is necessary to observe patients closely at least a few hours after endocrine stimulation test, and MR imaging may make an earlier diagnosis for the pituitary apoplexy since CT scan often shows no density change in the pituitary adenoma.
We report a case of adrenocortical tumor that coexisted with paragangliomas. A 35-year-old woman was admitted to the hospital because of left upper abdominal pain. A palm-sized mass was palpated at left upper quadrant. Hormonal studies revealed the features of pheochromocytoma. An emergency operation was performed because hemorrhage of the tumor was suspected. A 10cm diameter ruptured mass was found in the left adrenal area and other tumors were also noted adjacent to inferior vena cava (IVC). The pathologic report revealed that the adrenal mass was an adrenocortical tumor with hemorrhagic necrosis and that the tumors adjacent to IVC were paragangliomas. This was the first case of adrenocortical tumor with paragangliomas in our Medline search result, hence we report the case with a review of the literature.
This report presents a unique case of corticotroph cell adenoma in a 30-year-old man without acromegaly or features typical of Cushing's disease, who developed cavernous sinus syndrome following pituitary apoplexy. Magnetic resonance imaging revealed a large intrasellar/suprasellar mass with pituitary hemorrhage and extension of a hematoma to the anterior base of the skull. Urgent transnasal pituitary surgery revealed an acidophilic pituitary adenoma, with immunoreactivity for ACTH and GH and expression of proopiomelanocortin (POMC) and GH messenger ribonucleic acid (mRNA) demonstrated by in situ hybridization. To our knowledge, a silent corticotroph cell adenoma with GH production has never been reported. This type of adenoma may potentially enlarge and develop tumoral hemorrhage because it is free of endocrinological symptoms.
To investigate the effects of total abdominal hysterectomy on circulating leptin levels, 16 pre- and 8 postmenopausal patients with uterine leiomyoma or carcinoma in situ of the uterine cervix were enrolled. Serum levels of leptin and fasting blood sugar (FBS) were determined before (day -7) and after surgery (day +1 and +7). Body mass index (BMI) was recorded at day -7 and +7. Anesthesia duration, surgical duration, hematology, and blood loss during surgery were recorded. Relations of these variables to serum leptin levels were investigated. Serum leptin levels rose from 7.3±4.7ng/mL to 9.3±5.8ng/mL at day +1 (P<0.01), then decreased to 4.9±3.0ng/mL at day +7 (P<0.05 vs. values at day -7 and +1). FBS levels also rose from 89.4±7.5mg/dL to 119.3±24.0mg /dL (P<0.01), then returned to normal at day +7 (96.2±9.0mg/dL). However, there was no significant correlation observed between FBS and leptin levels at each time point (r≤0.22). BMI decreased from 22.7±3.0kg/m2 to 21.7±2.9kg/m2 at day +7 (P<0.001). At day -7 and +7, leptin levels were positively correlatd with BMI (r=0.79, P<0.001 and r=0.71, P<0.001, respectively). Circulating leptin levels were increased on day one after total abdominal hysterectomy.