Biomedical subjects

R Hoermann

Publications and source records attributed to R Hoermann.

At least 37 records · Page 2Linked to original sources

PubMed1996

Posterior retroperitoneoscopy as a new minimally invasive approach for adrenalectomy: results of 30 adrenalectomies in 27 patients.

Posterior retroperitoneoscopic adrenalectomy is a new minimally invasive method. It represents an alternative to conventional open procedures and laparoscopic techniques. Between July 1994 and November 1995 a total of 30 retroperitoneoscopic adrenalectomies were performed on 27 patients. In 24 patients, unilateral tumors were seen (size 1-7 cm): seven Cushing adenomas, five Conn adenomas, seven pheochromocytomas, four hormonally inactive tumors, one cyst. Three patients suffered from Cushing syndrome with bilateral adrenal gland hyperplasias (two inoperable pituitary gland tumors, one bronchial carcinoid with ACTH secretion). The operations were carried out in prone position. After balloon dilatation of the retroperitoneum and creation of a pneumoperitoneum the preparation of the adrenal gland was performed via three trocar sites positioned below the 12th rib. Twenty-five adrenalectomies were completed endoscopically, and five times (among four patients) conversion to the conventional posterior technique was necessary. The average operating time of complete endoscopic adrenalectomies was 124 minutes (45-225 minutes); blood loss was 10 to 120 ml. With minimal need for postoperative analgesia (average dosage 7.9 mg of piritramide), mobilization and adequate food uptake were possible on the day of operation. The posterior retroperitoneoscopic adrenalectomy is a relatively fast, safe method, with the advantages of the posterior open approach and minimally invasive surgery. It therefore represents an important addition to adrenal gland surgery.

Adenoma↗

PubMed1996

Enhanced functional activity in thyroid adenomas in vitro.

The majority of thyroid adenomas have been shown to be of clonal origin. In a portion of them, somatic or germline point mutations leading to altered TSH receptor or Gs alpha-proteins have been found. The constitutive activation of these proteins consecutively stimulate cAMP-levels. Expression of the TSH receptor mutants in mammalian cells leads to increased cAMP-production compared to cells transfected with the wild type receptor. Presently, the role of these mutations in the development and growth of such tumours is still unclear. In our own investigations we made an attempt to evaluate the functional significance of these observations. In nodular tissue derived from patients with functioning autonomous adenoma we found significantly higher basal and TSH stimulated thyroid hormone releasing activity than in the surrounding paranodular tissue and in thyroid tissue derived from patients with euthyroid goiter. These findings indicate a functional relevance of constitutively activated intracellular signal transducing cascade in thyroid adenomas that may lead to hyperthyroidism in the presence or absence of external thyroid stimulators.

Adenoma↗

PubMed1996

Stimulation of thyroidal and extrathyroidal thyrotropin receptors.

TSH receptor plays a pivotal role in the regulation of thyroid function and is intimately involved in the pathogenesis of common thyroid disorders. A lack of specificity and absence of down regulation upon stimulation renders the human TSH receptor susceptible to exogenous overstimulation, which forms the basis of hyperthyroidism in TSHoma, Graves' disease and gestational thyrotoxicosis. Further, TSH receptor activation in the absence of exogenous stimulators due to the expression of endogenously active mutant receptors has recently been described, and may in part account for hyperthyroidism in autonomously functioning thyroid nodules. Signal bifurcating by coupling of TSH receptor to different G proteins may be a likely mechanism to explain the multitude of distinct effects caused by TSH receptor activation including mainly hormone production and growth promotion. Also, TSH receptor appears to mediate immunological stimulation, its activation by TSH R Ab inducing expression of adhesion molecules and HLA class II antigens on thyrocytes. Increasing evidence suggests that TSH receptor is not restricted to thyroid and may be expressed in extrathyroidal tissues with a potential role in the pathogenesis of Graves' orbitopathy.

Humans↗

PubMed1996

Human chorionic gonadotropin-beta in the differentiation of malignancy-related and nonmalignant ascites.

The clinical value of the tumor marker human chorionic gonadotropin-beta (hCG-beta) in ascitic fluid for the differentiation of malignancy-related and non-malignant ascites was evaluated. Ascitic fluid protein, cholesterol and cytological examination were determined for comparison. Thirty-six patients with malignancy-related ascites (27 peritoneal carcinomatosis, 9 miscellaneous malignant causes without peritoneal carcinomatosis) and 69 patients with nonmalignant ascites (55 with liver cirrhosis, 14 with miscellaneous nonmalignant causes) were investigated. hCG-beta concentrations were elevated in malignant samples and with a cut-off value of 10 mIU/ml hCG-beta yielded a sensitivity of 61%, specificity of 94% and efficiency of 83%. Ascitic fluid protein (cut-off value 3.0 g/100 ml) and cholesterol (cut-off value 45 mg/100 ml) concentrations showed a sensitivity of 64%/83%, specificity of 77%/81% and efficiency of 72%/82%. The combination of hCG-beta and cytological examination yielded 89.5% differential diagnostic efficiency, superior to the combinations of protein and cytology or protein and hCG-beta. hCG-beta tended to be superior to protein/cholesterol determination regarding sensitivity (44% vs. 11%/33%) and specificity (79% vs. 50%/57%) in the subgroups of patients with miscellaneous causes of ascites. In conclusion, hCG-beta is frequently elevated in malignancy-related ascites and seems to be as useful a parameter as total protein for the differentiation of malignancy-related from nonmalignant ascites.

Ascites↗

PubMed1996

Expression of the human chorionic gonadotropin-beta gene cluster in human pituitaries and alternate use of exon 1.

Previous studies have indicated that in addition to other glycoprotein hormones, the pituitary gland produces small amounts of hCG beta, the classical pregnancy and tumor marker. At the gene transcription level, definitive proof for hCG beta messenger ribonucleic acid transcription was still lacking, largely due to the 90% homology to hLH beta at the DNA sequence level, which renders specific hCG detection in the presence of a vast excess of LH difficult. We investigated both the presence of hCG beta messenger ribonucleic acid and the protein itself in normal human female postmenopausal (n = 4) and male pituitaries (n = 2). Reverse transcription-PCR and subsequent restriction enzyme analysis revealed that the hCG beta 3, 5, 7, and 8 genes coding for genuine hCG beta were transcribed in all pituitaries. Additionally, three alternatively spliced gene products derived from hCG beta genes 1 and 2 were detected and verified by single strand sequencing of the complementary DNAs. The most abundant fragment (244 bp) showed a point mutation (T-->A) in the splice donor site for the first intron, resulting in an alternate use of exon 1 and a frame shift in the open reading frame that might give rise to a hypothetical protein, 132 amino acids in length. With regard to protein synthesis, we confirmed the pituitary as the site of production for hCG beta by reverse phase high performance liquid chromatography and subsequent immunoradiometric assays, including a monoclonal antibody directed against the unique C-terminal extension of hCG beta.

Aged↗

PubMed1995

Crude urinary human chorionic gonadotropin contains variant forms of HCG with low sialic acid content that exhibit an increased thyrotropic activity in CHO cells expressing the human TSH receptor.

Hyperthyroidism occurs in association with pregnancy or trophoblastic tumours. This is due to the secretion of thyroid stimulators by trophoblastic cells, most likely hCG or a variant form of hCG. In the present studies we sought to identify hCG variants with enhanced thyrotropic activity contained in crude hCG extract from pregnancy urine (hCGc). Such studies seem now feasible, because highly sensitive assays employing CHO cells transfected with the recombinant human TSH receptor recently became available. Initially, we found the activity of hCGc to both inhibit the binding of 125I-bTSH to CHO-TSHr cells and to stimulate the cAMP release by the cells to be increased, compared to highly purified hCG (hCGp), which was tested in comparable immunological concentrations. We then processed hCGc on a DEAE-52 anionexchange column to separate materials of interest, termed hCGv, from hCGp. HCGv was further purified by gel chromatography, and found to be enriched in terms of both, its holo-hCG immunoactivity and its TSH binding inhibiting activity, compared to hCGc where it was derived from. It also proved more potent than hCGp to bind to recombinant hTSH receptor and to stimulate adenylate cyclase activity in CHO-TSHr cells. Enzymatic desialylation was able to increase the potency of both hCGv and hCGp, and rendered the two desialylated hCG forms nearly equipotent. Isoelectric focusing and direct measurement of sialic acid contents revealed hCGv to be less sialylated than hCGp.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Immunoreactive human chorionic gonadotropin beta core fragment in human pituitary.

The human pituitary has been shown to produce small amounts of immunoreactive human chorionic gonadotropin (hCG) and its alpha- and beta- subunit (hCG alpha, hCG beta). The aim of the present studies was to further examine the various hCG-related materials in the human pituitary, particularly to search for the existence of pituitary hCG beta core fragment (hCG beta cf)--like material. HCG beta cf has been found in the urine of pregnant women, patients with trophoblastic tumors and also in postmenopausal women. Gel chromatography of pituitary extract on Superdex 200 showed three distinct peaks of hCG-related immunoreactivities, i.e. hCG, hCG beta and hCG beta cf, which were distinguishable from hLH and hLH beta peaks. HCG beta cf was recognized by a specific immunometric assay (crossreactivities with hCG beta 0.016%, hLH beta 0.04%), but unreactive in an hLH + hLH beta assay. It was purified and displayed physical properties similar to those of hCG beta cf derived from pregnancy urine. Apart from immunological differences between the small molecular weight forms or fragments of hCG and LH origin, reversed phase HPLC was able to physically discriminate between hCG beta cf and hLH beta fragment. The latter was much more abundant than the former in the pituitary extract. HCG beta cf showed microheterogeneity related to its sialic acid content. In conclusion, the present data indicate that immunoreactive hCG beta cf is present in human pituitary extracts. The physical and immunological properties of pituitary hCG beta cf are distinguishable from those of the more abundant hLH beta and its fragment, and compare favorably with those of urinary hCG beta cf of trophoblastic origin.

Aged↗

PubMed1995

Measurement of human chorionic gonadotropin-related immunoreactivity in serum, ascites and tumour cysts of patients with gynaecologic malignancies.

Human chorionic gonadotropin (hCG)-like molecules have been reported to be elevated in a substantial fraction of serum samples from patients with various gynaecologic tumours and have been discussed as possible markers in these malignancies. Employing highly sensitive and specific immunoradiometric assays, we determined total hCG-related immunoreactivity (hCG/hCG beta), as well as free alpha-subunit (alpha-SU), common to all glycoprotein hormones, in serum (n = 106) and malignant effusions (n = 26) of women with gynaecologic malignancies. For comparison, we also measured hCG/hCG beta in nonmalignant ascitic fluids (n = 21). HCG/hCG beta serum levels were elevated (> 5 IU L-1) in 39 of 106 patients (37%) with gynaecologic malignancies, whereas free alpha-SU was above normal range only in seven (6.6%). Frequencies of hCG/hCG beta elevations were similar in women with endometrial, (n = 39), cervical (n = 40) and ovarian (n = 27) cancer, being 30%, 35% and 41%, respectively. In malignant ascites (n = 15) and tumour cyst fluids (n = 11) of patients with ovarian cancer, hCG/hCG beta concentrations were significantly higher than in the corresponding serum samples and benign ascitic samples. Free alpha-SU, on the other hand, was increased in only one of 26 malignant effusions. In conclusion, hCG/hCG beta is frequently elevated in serum of patients with endometrial, cervical and ovarian cancer and may serve as a tumour marker in these malignancies, particularly in patients where other markers are negative. In this respect, analysis of ascitic or tumour cyst fluids may be of higher diagnostic value as serum measurements.

Adult↗

PubMed1995

Variation in the thyrotropic activity of human chorionic gonadotropin in Chinese hamster ovary cells arises from differential expression of the human thyrotropin receptor and microheterogeneity of the hormone.

The role of hCG as a stimulator of the human thyroid has been a subject of controversy, because discrepant results have been obtained in different in vitro assays. In an attempt to explain the variation observed in the thyroid response to hCG, we investigated the ability of hCG and that of its isoforms and glycosylation variants to inhibit [125I]bovine (b) TSH binding and stimulate adenylate cyclase in two clones, JP09 and JP26, of Chinese hamster ovary cells stably transfected with the human TSH receptor (hTSHr). The two clones differed with respect to the number of hTSHr expressed per cell (34,000 in JP09 and 2,000 in JP26 cells). Both responded extremely well to bTSH; the cAMP response to 0.001 IU/L bTSH was distinguishable from basal values. Interestingly, JP09 cells were readily stimulated by hCG (20-100 mg/L; 0.52-2.6 x 10(-6) mol/L) to release cAMP, whereas JP26 cells showed little if any response. Also, cAMP stimulation produced by asialo-hCG was 12-fold in JP09 cells and only 4-fold in JP26 cells compared to 45- and 67-fold stimulations by bTSH, respectively. Stimulation by asialo-hCG was approximately 30% that of bTSH in JP09 cells, but less than 6% in JP26 cells. When assessing the thyrotropic activity of the microheterogeneous isoforms of hCG, more alkaline pI forms were found to be more active than those of a more acidic pI regardless of whether they were derived from normal or molar pregnancy urine. Further studies with hCG, asialo-hCG, asialoagalacto-hCG, and deglycosylated hCG revealed that removal of sialic acid caused a marked increase in both its affinity for hTSHr and its cAMP-releasing potency, whereas removal of further carbohydrate, although it slightly enhanced receptor binding, was detrimental to adenylate cyclase activation. In conclusion, differences in hTSHr expression may cause a variation in the cAMP response to hCG or its glycosylation variants, as does the microheterogeneity of the hormone itself. These mechanisms may be responsible at least in part for the divergent responses of different cell types to hCG and render interpretation of the physiological meaning of the data obtained in recombinant receptor systems difficult.

Animals↗

PubMed1995

Spontaneous regression of hepatocellular carcinoma.

Spontaneous regression of cancer is a rare phenomenon seldom described in patients with hepatocellular carcinoma. A case of spontaneous regression of hepatocellular carcinoma is reported and compared with the reports published in the English literature. A 52-yr-old man presented with biopsy-proven hepatocellular carcinoma, which was considered to be unresectable at initial laparotomy. The tumor subsequently regressed without specific treatment, as assessed radiologically and by normalization of a previously elevated alpha-fetoprotein level. At repeat laparotomy 14 months after initial diagnosis, intraoperative ultrasound failed to disclose a hepatic mass, and multiple biopsies showed no evidence of malignancy. To date, only nine case reports of apparently spontaneous regression of hepatocellular carcinoma have been published in the English literature. Clinical characteristics discriminating these patients from less fortunate patients with hepatocellular carcinoma could not be identified. The mechanisms underlying this intriguing phenomenon remain unknown.

Biopsy↗

PubMed1994

Alpha-subunit and human chorionic gonadotropin-beta immunoreactivity in patients with malignant endocrine gastroenteropancreatic tumours.

In the serum of patients with malignant endocrine gastroenteropancreatic (GEP) tumours, both alpha-subunit (alpha-SU), common to all glycoprotein hormones, as well as free beta-subunit of human chorionic gonadotropin (hCG-beta) have been reported to be elevated in a substantial fraction. Both have been discussed as markers of malignancy in these neoplasms. In the present study we evaluated the diagnostic significance of alpha-SU and hCG-beta as serum markers in patients with malignant endocrine gastroenteropancreatic tumours. The study group consisted of 52 patients with endocrine GEP-malignancies (24 nonfunctioning, 23 carcinoid syndromes, four gastrinoma, one glucagonoma), located in the small intestine (n = 29), pancreas (n = 17), colon or rectum (n = 3), retroperitoneum (n = 2) and stomach (n = 1). alpha-SU and hCG-beta immunoreactivity was also assessed in the serum of patients with benign GEP-tumors (five insulinoma, and three gastrinoma). Concentrations of alpha-SU and hCG-beta were determined using two highly sensitive and specific immunoradiometric assays employing two monoclonal antibodies each. In 19 of 52 patients (37%), either alpha-SU (n = 9), hCG-beta (n = 7) or both subunits (n = 3) were elevated. In the subgroup of 24 patients with nonfunctioning GEP-tumours, increased concentrations of either alpha-SU (n = 6) or hCG-beta(n = 3) or both subunits (n = 1) were found in 10 of 24 patients (42%). In four of 23 patients with carcinoid syndrome (17%), either alpha-SU (n = 2), hCG-beta(n = 1) or both subunits (n = 1) were above the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Interaction of human chorionic gonadotropin (hCG) and asialo-hCG with recombinant human thyrotropin receptor.

hCG is a putative thyroid stimulator. The present studies were undertaken to examine its interaction and that of its desialylated variant asialo-hCG with recombinant human TSH (hTSH) receptor (hTSHr). To this end, we transfected a human thyroid carcinoma cell line (HTC) lacking endogenous TSHr with the full-length cDNA of the hTSHr. Unlike the wild type, the transfected cells, termed HTC-TSHr cells, were able to bind bovine TSH (bTSH) with high affinity and increase cAMP production in response to bTSH stimulation. Of the hCG forms, intact hCG displayed a weak activity to inhibit [125I] bTSH binding to HTC-TSHr cells, with 100 mg/L (2.6 x 10(-6) mol/L) producing maximally a 20% inhibition, whereas asialo-hCG achieved half-maximum binding inhibition at a concentration of 8 mg/L (2.3 x 10(-7) mol/L). The inhibitory constant (Ki) of asialo-hCG for recombinant hTSHr was calculated from saturation experiments in the presence of variable doses of bTSH and a fixed concentration of asialo-hCG to be approximately 8 x 10(-8) mol/L. The interaction of asialo-hCG with TSHr was further assessed by studies of the direct binding of the radioactively labeled hormone to both HTC and HTC-TSHr cells. [125I]Asialo-hCG binding to HTC-TSHr cells was 4.7%, compared to 1.5% in the wild-type cells lacking TSHr and was displaceable by bTSH (0.1-100 IU/L), indicating specific binding of the tracer to TSHr. Functionally, hCG (up to 100 mg/L; 2.6 x 10(-6) mol/L) proved unable to evoke any significant cAMP response over basal values in HTC-TSHr cells, as did asialo-hCG. Asialo-hCG, but not hCG, inhibited bTSH-stimulated adenylate cyclase activity in the cells in a dose-dependent manner. In conclusion, the present data show that intact hCG binds only weakly to HTC-TSHr cells and produces no significant cAMP stimulation, which is at variance with data obtained in FRTL-5 and Chinese hamster ovary-TSHr cells, but in good accord with previous findings in human thyroid membranes. Asialo-hCG, on the other hand, strongly binds to recombinant TSHr and inhibits the cAMP response to bTSH in HTC-TSHr cells, indicating that the desialylated hCG variant directly interacts with the receptor and truly is an antagonist of the hTSHr.

Asialoglycoproteins↗

PubMed1994

Systemic iodine absorption during endoscopic application of radiographic contrast agents for endoscopic retrograde cholangiopancreaticography.

Hyperthyroidism induced by contrast agents in a major problem in patients with pre-existing thyroid disease, particularly in patients with functional thyroid autonomy. The present study was undertaken to evaluate whether contrast media applied during endoscopic retrograde cholangiopancreaticography (ERCP) may result in a significant increase of serum iodine levels and thus may be associated with the risk of iodine-induced hyperthyroidism. The courses of serum concentrations of total iodine and free iodide, as well as of urinary iodine excretion, were measured in 15 patients before and up to 21 days after ERCP. During ERCP, the non-ionic contrast medium iopamidol was instilled in amounts resulting in a total iodine load of 57.4 +/- 22.8 mmol (7.3 +/- 2.9 g). In all patients, ERCP resulted in a highly significant increase in serum levels of total iodine from 0.8 +/- 0.5 to 85.2 +/- 116.9 mumol/l 4 h after application of the contrast agent. In parallel, serum iodide levels were raised from 0.06 +/- 0.04 to 5.42 +/- 6.09 mumol/l and urinary iodine excretion from 71.1 +/- 35.7 mumol/mol creatinine to 621,620.9 +/- 636,492.2 mumol/mol creatinine. Peak concentrations of serum iodine are well related to the total amount of iodine applied (p < 0.05). During follow-up, iodine levels returned to pre-exposure levels within 2-3 weeks. Levels of thyrotropin, free thyroxine, and free triiodothyronine remained unchanged during the follow-up period. In conclusion, endoscopic application of iodinated contrast agents during ERCP leads to significant increases of serum levels of total iodine and free iodide and of urinary iodine excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1994

Immunological recognition and clinical significance of nicked human chorionic gonadotropin in testicular cancer.

We studied the physical properties, immunological recognition, and clinical significance of nicked human chorionic gonadotropin (hCGn) in testicular cancer. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions, the beta-subunit of hCGn (hCG beta n) dissociated into two peptides, and, by reversed-phase chromatography, hCG beta n was found to be less hydrophobic than hCG beta. Immunologically, hCGn lacked two epitopes specific for holo-hCG (c1, c2), whereas at least five hCG beta epitopes (beta 1-beta 5) were preserved, and, as a result, recognition of hCGn by different hCG assays varied widely. In 309 sera and 88 urine samples from patients with seminomatous or nonseminomatous testicular cancer, hCG-only, hCG+hCGn, and hCG+hCGn+hCG beta+hCG beta n+hCG beta core-fragment assays gave parallel results. hCGn was more abundant in urine than in serum samples. In conclusion, hCGn lacks two conformationally dependent epitopes of hCG, causing a change in hydrophobicity and explaining its failure to react in certain holo-hCG assays. Recognition of hCGn, however, does not seem to be crucial in the routine use of serum hCG as a tumor marker in patients with testicular cancer.

Chemical Phenomena↗

PubMed1993

Increased binding capacity of receptors for the epidermal growth factor in benign thyroid nodules and thyroid malignancies.

To determine the role of epidermal growth factor (EGF) receptors in thyroid tumorigenesis, EGF binding was compared in membranes from malignant and from benign thyroid tumors. Surgical specimens were obtained from 28 patients with thyroid carcinomas (3 papillary, 13 follicular, 6 undifferentiated, and 6 medullary carcinomas) and from 30 patients with benign thyroid tumors (15 scintigraphically functional and 15 nonfunctional nodules). In 30 cases normal tissue adjacent to the tumor was also obtained. EGF binding was seen to be increased not only in thyroid carcinomas but also in benign thyroid tumors, particularly in functional thyroid adenomas. The highest EGF binding was found in undifferentiated carcinomas. A direct comparison of the EGF binding characteristics in tumor and adjacent normal thyroid tissue revealed that the increased binding of EGF is due mainly to an increase in the number of binding sites rather than an alteration in receptor affinities. EGF binding capacities were 18.4 +/- 16.7 fmol/mg protein in thyroid carcinomas and 10.5 +/- 5.2 fmol/mg in the corresponding normal tissue (P < 0.05, Kd 0.84 +/- 0.26 nM, n = 11). In autonomously functioning thyroid adenomas binding capacities were 14.2 +/- 8.2 fmol/mg in the nodules and 8.9 +/- 4.8 fmol/mg in normal tissue (P < 0.01, Kd 0.73 +/- 0.62 nM, n = 15). In conclusion, EGF receptor levels are increased not only in malignant thyroid tumors but also in well-differentiated benign thyroid nodules.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Molecular heterogeneity of human chorionic gonadotropin in serum and urine from patients with trophoblastic tumors.

Many studies on the structure and function of human chorionic gonadotropin (hCG) have relied on purified hCG preparations obtained from pregnancy urine. In the present studies, in order to demonstrate possible differences between the hCG species present in serum and those released into urine, we examined serum and urinary samples derived from patients with trophoblastic tumors and of pregnancy origin by sodium dodecyl sulfate electrophoresis, isoelectric focusing, and two-dimensional electrophoresis including immunostaining with a specific hCG antibody and densitometry of the protein bands. This type of analysis was presently feasible only in patients presenting with extremely high serum levels of hCG and was therefore limited to seven patients with testicular cancers, one woman with a hydatidiform mole, and one pregnancy sample. We found marked differences in the isoelectric focusing pattern between urinary and serum hCG samples, with the urinary hCG consisting of more alkaline pI variants than that present in the serum of the same patients. Tumor hCG differed from pregnancy hCG in that it contained more acidic variants, and this was true for urinary and serum-derived materials. In some tumor and pregnancy samples an hCG immunoreactive material of lower molecular weight than hCG itself was found. In conclusion, the present studies, extending previous findings on the microheterogeneity of hCG, indicate that serum and urinary-derived hCG may differ in the composition of the isoform spectrum, as does tumor and pregnancy hCG. Further, in some patients hCG immunoreactive molecules exist that differ markedly from hCG in size and charge. These observations suggest that, whenever possible, serum-derived hCG materials should be used to define the molecular structure of hCG and assess its biological activities.

Adult↗

PubMed1993

Thyroid stimulation by placental factors.

There is now convincing evidence that the human placenta produces factors which have some role in regulating maternal thyroid function during normal pregnancy and are capable of inducing overt hyperthyroidism in some pregnant women and in patients with trophoblastic tumors. As far as the biochemical nature of these placental thyroid stimulators is concerned, a bulk of evidence indicates that hCG, which is abundant in the blood of pregnant women and patients with trophoblastic diseases and shares some structural similarities with human TSH, is the putative thyroid-stimulating factor. However, it is disturbing that most in vitro studies have failed to prove that hCG is truly capable of stimulating the human thyroid. Therefore, factors other than hCG have also to be considered, particularly some molecular variant forms of hCG with enhanced thyrotropic activity. Both the existence of tumor-associated hCG variants in patients with trophoblastic diseases and their ability to stimulate thyroid hormone release in human thyroid tissue have been demonstrated. To complicate things further, other variants of hCG have been identified and purified from pregnancy urine that have a thyroid inhibitory effect in human thyroid membranes. The variant forms of hCG have been shown to differ from the native hormone mainly in the carbohydrate moiety, with the more acidic, more glycosylated variants being the ones capable of stimulating the human thyroid and the more alkaline sialic acidic deficient variants on the other hand, being potent thyroid inhibitors. Future studies should reveal if the different thyroid stimulators and thyroid inhibitors may possibly interact with specific regions of the human TSH receptor that confer their respective functional activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Factors↗

PubMed1993

Inhibition of functional and immunological responses to thyroid-stimulating antibodies from patients with Graves' disease by blockade of the thyrotropin receptor.

Thyrotropin (TSH) receptor is the main autoantigen and the target of thyroid-stimulating antibodies in Graves' disease. In the present studies, in order to shed further light on the role of TSH receptor in thyroid autoimmune disease, we investigated the effects of TSH receptor blockade on functional and immunological responses to thyroid stimulation by Graves' immunoglobulins in the nude mouse bearing human thyroid transplants. Injecting the nude mice with purified Graves' immunoglobulins G resulted in a dose-dependent stimulation of thyroid hormone production, an inducement of cellular hypertrophy of transplant thyrocytes, and an expression of the HLA-DR antigen by up to 75% of the transplant thyroid follicular cells. Treatment of the animals with the TSH receptor antagonist asialoagalacto-hCG was able to inhibit the stimulation by Graves' immunoglobulins G of thyroxine production, cellular hypertrophy of transplant thyrocytes, and HLA-DR expression by thyroid follicular cells in the human transplants. The present data provide direct evidence for an involvement of the human TSH receptor in mediating both the functional disturbance (hyperthyroidism) and the immunological disorder in Graves' disease and add further support to the concept of using TSH receptor antagonists in the management of the disease.

Animals↗