Γ-MELANOTROPHIN-LIKE IMMUNOREACTIVITIES IN HUMAN PITUITARIES, ACTH-PRODUCING PITUITARY ADENOMAS, AND ECTOPIC ACTH-PRODUCING TUMOURS: EVIDENCE FOR AN ABNORMALITY IN GLYCOSYLATION IN ECTOPIC ACTH-PRODUCING TUMOURS

Using gel exclusion chromatography on Bio-Gel P-60, gamma-melanotropin-like immunoreactivity (gamma-MSH-LI) in three human pituitary glands, two ACTH-producing pituitary adenomas, and three ectopic ACTH-producing tumours (two medullary thyroid carcinomas and one thymoma) was divided into one or two molecular weight classes. The largest component eluted near the position of mouse 16K fragment and was designated big gamma-MSH-LI. This big gamma-MSH-LI was present in all samples. The second one, designated intermediate gamma-MSH-LI, eluted between the position of mouse 16K fragment and human ACTH, and was demonstrated only in two ectopic ACTH-producing tumours. No gamma-MSH-LI emerged at the elution position of synthetic gamma 3-MSH. Affinity chromatography on concanavalin A-agarose revealed that a significant fraction (52-68%) of gamma-MSH-LI from human pituitary glands, ACTH-producing pituitary adenomas, and one ectopic ACTH-producing tumour bound to the column and was eluted with alpha-methyl-D-mannopyranoside. In two ectopic ACTH-producing tumours which contained big and intermediate gamma-MSH-LI, a relatively small fraction (27-35%) of gamma-MSH-LI bound to the column and was similarly eluted. These observations suggest that human gamma-MSH-LI is glycosylated and that there is an abnormality in the glycosylation of gamma-MSH-LI in some ectopic ACTH-producing tumours.     

Presence of immunoreactive gamma-melanocyte-stimulating hormone, adrenocorticotropin, and beta-endorphin in human gastric antral mucosa

gamma MSH-like, ACTH-like, and beta-endorphin-like immunoreactivities (gamma MSH-LI, ACTH-LI, and beta-endorphin-LI, respectively) were detected in water extracts of four human gastric antral mucosa. The concentrations of gamma MSH-LI, ACTH-LI, and beta-endorphin-LI in the boiling water extracts were 9.9 +/- 3.3, 6.2 +/- 1.8, and 3.9 +/- 1.3 ng/g (mean +/- SE), respectively. Gel exclusion chromatography on a Bio-Gel P-60 column showed that most ACTH-LI and beta-endorphin-LI were eluted at the elution positions of human ACTH and beta-endorphin, respectively. The major peak of gamma MSH-LI was eluted at the elution position of big gamma MSH-LI, but another peak was eluted at the elution position of small gamma MSH-LI, as in bovine intermediate pituitary. Concanavalin A-agarose affinity chromatography showed that 52% of gamma MSH-LI was specifically bound to the column, but only 8% of ACTH-LI and none of beta-endorphin-LI were specifically bound. These results suggest that there exists an ACTH/beta-lipotropin common precursor protein in human antral mucosa and that the processing of the precursor is accelerated as a bovine intermediate pituitary, indicating possible roles of these peptides in the function of the gastrointestinal tract.     

Evidence for gamma-MSH-like immunoreactivity in ectopic ACTH-producing tumors

Using a specific radioimmunoassay for gamma-MSH, a predicted peptide in the cryptic N-terminal portion of the adrenocorticotropin-beta-lipotropin precursor, gamma-MSH-like immunoreactivity (gamma-MLI) was detected in two ectopic ACTH producing tumors. Gel chromatographic studies on Bio-Gel P-60 revealed one or two peaks of gamma-MLI; one was eluted near th elution position of beta-LPH, compatible with gamma-MLI in human pituitary and the other emerged near the position of beta-endorphin. These results indicate that ectopic ACTH-producing tumors eleborate not only ACTH, beta-endorphin but also gamma-MLI.     

The major immunoreactive alpha-melanocyte-stimulating hormone (alpha MSH)-like substance found in human fetal pituitary tissue is not alpha MSH but may be desacetyl alpha MSH (adrenocorticotropin1-13NH2)

Pituitary glands were obtained from human abortuses during the second half of gestation. Acid extracts were made from the anterior and neurointermediate lobes, and alpha MSH immunoreactivity (alpha MSHi) was quantified by RIA. alpha MSHi was found in both lobes of the pituitary gland, with 20-80% of the total pituitary alpha MSHi being present in extracts of the anterior lobe. Anterior and neurointermediate lobe extracts subjected to gel filtration on Sephadex G-50 revealed one peak of alpha MSHi having an elution profile identical to those of alpha MSH and desacetyl alpha MSH (ACTH1-13NH2). To characterize further the alpha MSHi extracts were subjected to high pressure liquid chromatography. No alpha MSH could be identified in extracts of the anterior lobe, and most of the alpha MSHi had an elution profile identical to that of desacetyl alpha MSH. Although small amounts of alpha MSH might be present in the neurointermediate lobe, most of the alpha MSHi in this lobe coeluted with desacetyl alpha MSH. Since alpha MSH was not converted to desacetyl alpha MSH during the extraction and chromatographic procedures, we hypothesize that the predominant form of alpha MSH-like material in the human fetal pituitary gland may be desacetyl alpha MSH.     

Immunocytochemical evidence for the presence of gamma 1-MSH-like immunoreactivity in pituitary corticotrophs and ACTH-producing tumours

The presence of gamma 1-MSH has been demonstrated in bovine neuro-intermediate lobe by biochemical methods, thus suggesting that this peptide is cleaved from the cryptic region of pro-opiocortin. In this study we report the localisation of gamma 1-MSH-like immunoreactivity in the adenohypophysis of man, ox, pig, dog and guinea-pig using immunocytochemical procedures at both light and electron microscope levels. Antisera recognising the C-terminal Arg-Phe-amide and the C-terminal penta-peptide-amide of gamma 1-MSH have been used throughout this study. The immunostaining was found in all endocrine cells of the pars intermedia (where present) and in scattered cells of the pars distalis identified as corticotrophs. No gamma 1-MSH immunoreactivity was detected in rat adenohypophysis. In addition, 7 ACTH-producing tumours (1 pituitary adenoma and 6 ectopic) were investigated and shown to contain gamma 1-MSH immunoreactive cells.     

Calcitonin in human gastric mucosa and carcinoma

Summary The localization of immunoreactive calcitonin (IR-CT) in the human gastric mucosa and tumor tissues was studied using an immunohistochemical peroxidase-antiperoxidase method. A small number of IR-CT-containing cells were observed in both infant and adult gastric antral mucosa and the ratio of IR-CT-containing cells to G cells was about 1:50-100. Moreover, tissue content of IR-CT in normal antral mucosa was 2.37±0.35 ng/g wet weight. IR-CT-containing cells and G cells decreased with the progress of chronic atrophic gastritis and were totally absent in intestinal metaplastic glands. IR-CT was detected in G cells, suggesting a paracrine relation between gastrin and CT. IR-CT was not found in tumor cells of 35 gastric adenomas and 40 well differentiated adenocarcinomas. On the other hand, it was demonstrated in a very small number of tumor cells in 4 of 46 poorly differentiated adenocarcinomas, and in a good number in 3 of 7 scirrhous argyrophil cell carcinomas. IR-CT in plasma could serve, therefore, as a tumor marker of scirrhous endocrine cell carcinoma, and its production in cancer cells was considered to be eutopic rather than ectopic.Supported in part by Grant-in Aid for Cancer Research from the Ministry of Education, Science and Culture (No. 59010074).     

Size heterogeneity of beta-MSH in ectopic ACTH-producing tumors: presence of beta-LPH-like peptide.

Gel chromatographic, immunologic and biologic properties of beta-melanocyte-stimulating hormone (beta-MSH) in tumor tissues obtained from eight patients with the ectopic ACTH syndrome were studied and compared to those of pituitary beta-MSH. Size heterogeneity of immunoreactive beta-MSH was found in all the tumors studied as well as in normal human pituitaries. Both the tumors and pituitaries contained immunoreactive beta-MSH of a larger molecular size than the well-characterized beta-MSH of small molecular size. The large molecular weight beta-MSH also predominated in the plasma. It was found to be bioactive by an in vitro MSH assay, immunologically indistinguishable from human beta-MSH, and chromatographically very similar to beta-lipotropic hormone (beta-LPH). Tryptic digestion of the large molecular weight beta-MSH under controlled conditions promptly produced bioactive beta-MSH of small molecular size, followed by the appearance of immunologically active but biologically inert fragments. These results suggest that the ectopic ACTH-producing tumor as well as the pituitary elaborate beta-LPH-like peptide which might be the predominant component of immunoreactive beta-MSH in man.     

An ectopic ACTH-producing carcinoid tumor localized by the measurement of ACTH in the bronchial lavage

We report a case of an ectopic ACTH-producing carcinoid in the lung. Typical Cushingoid appearance, elevated plasma ACTH and serum cortisol, bilateral enlargement of the adrenal glands, absence of pituitary adenoma and negativity in petrosus sinus venous sampling indicated the ectopic ACTH syndrome. Venous samplings from a lung tumor which was detected by the chest X-ray, did not show any step-up of ACTH. However, ACTH concentration in the bronchoscopic lavage was as high as that in the peripheral blood. Removal of the tumor, which was an ACTH producing carcinoid, resulted in normalization of ACTH and cortisol concentrations. Measurement of ACTH in the bronchoscopic lavage was useful for the diagnosis of ectopic ACTH-producing tumor.     

Human beta-melanocyte-stimulating hormone revisited.

It is generally accepted that human beta-melanocyte-stimulating hormone (h beta MSH) does not normally exist in humans but was merely an artifactually generated 22-amino acid peptide corresponding to a lipotropin (LPH) fragment (residues 35-56). We examined whether the shorter 18-amino acid peptide h beta MSH-(5-22) could be detected in some human tissues. Normal human pituitaries and hypothalami as well as corticotropin-secreting pituitary and nonpituitary tumors were extracted and chromatographed on Sephadex G-50, and the fractions were measured with two radioimmunoassays using either a COOH-terminal human gamma LPH (h gamma LPH) antiserum that recognized equally h gamma LPH, h beta MSH, and h beta MSH-(5-22) or a mid-portion h gamma LPH antiserum that recognized h gamma LPH and h beta MSH but not h beta MSH-(5-22). Normal pituitaries and pituitary tumors contained a single immunoreactive material coeluting with h gamma LPH. The hypothalami and the nonpituitary tumors all contained h gamma LPH and a smaller molecular weight material that was only detected in the COOH-terminal h gamma LPH radioimmunoassay; its elution volume (Ve/V, 0.75) was identical to that of h beta MSH-(5-22) but different from that of h beta MSH (Ve/V, 0.60); on reversed-phase HPLC, it coeluted with synthetic h beta MSH-(5-22) with a retention time different from that of h beta MSH. It is concluded that h beta MSH-(5-22) that corresponds to the 18-amino acid peptide h beta LPH-(39-56), flanked by two pairs of basic amino acids within the h beta LPH molecule, is a normal maturation product of proopiomelanocortin in human nonpituitary tissues.     

The antral mucosa as a new site for endocrine tumors in multiple endocrine neoplasia type 1 and Zollinger-Ellison syndromes

Carcinoid tumors were identified in the antro-pyloric mucosa of four patients with multiple endocrine neoplasia type 1 (MEN-1)/Zollinger-Ellison syndrome, accounting for 8.7% of 46 patients with this condition examined by endoscopy and histology. In contrast, no tumors were found in the antral biopsies from 124 cases of sporadic Zollinger-Ellison syndrome (P < 0.001), indicating a prominent role for the MEN-1 gene defects in tumor development. Immunohistochemically the tumors did not express the hormones produced by antral endocrine cells (gastrin, somatostatin, serotonin). In contrast, two of them were diffusely immunoreactive for the isoform 2 of the vesicular monoamine transporter (VMAT-2), a marker specific for the gastric nonantral enterochromaffin-like (ECL) cells. In one of these patients a second antral VMAT-2-positive carcinoid was seen 21 months after the first diagnosis. The other two antral carcinoids were unreactive for VMAT-2. Multiple ECL cell tumors were found in the gastric body-fundus mucosa of the two patients with VMAT-2-positive, but not in those with VMAT-2-negative, antral carcinoids. In one case, the former tumors were diagnosed 22 months after the detection of the antral tumor. We conclude that the antral mucosa is an additional tissue that may harbor endocrine tumors in MEN-1 syndrome. These tumors did not express the phenotype of normal antral endocrine cells and, in at least two cases, were identified as ectopic ECL cell carcinoids.     

Glial-derived neurotropic factor and RET gene expression in normal human anterior pituitary cell types and in pituitary tumors

Glial-derived neurotropic factor (GDNF) signaling is mediated through a 2-component system consisting of the so-called GDNF receptor-alpha (GFRalpha1), which binds to GDNF. This complex activates the tyrosine kinase receptor RET. In this paper we demonstrate GDNF, GFRalpha1, and RET mRNA and protein expression in the human anterior pituitary gland. Double immunohistochemistry of anterior pituitary sections showed GDNF immunoreactivity in more than 95% of somatotrophs and to a lesser extent in corticotrophs (20%); it was almost absent in the remaining cell types. Also, although more than 95% of somatotrophs were stained for RET, no positive immunostaining could be detected in other cell types. Furthermore, we have looked for GDNF and RET in human pituitary adenomas of various hormonal phenotypes. Strong positive immunostaining was found for c-RET in all of the GH-secreting adenomas screened as well as in 50% of ACTH-producing adenomas. Positive immunostaining for GDNF was found in all of the GH-secreting adenomas and in 10% of the corticotropinomas. Lastly, we found strong positive immunostaining for GFRalpha1 in 90% of the somatotropinomas and 50% of the corticotropinomas as well as in 1 of 8 prolactinomas and 1 of 13 nonfunctioning adenomas. All of the remaining pituitary tumors screened were negative for RET, GDNF, and GFRalpha1. This study indicates that GDNF may well be acting in the regulation of somatotroph cell growth and/or cell function in the normal human anterior pituitary gland. The expression of RET in all of the somatotropinomas and in 50% of the ACTH-producing tumors implies that GDNF and RET could be involved in the pathogenesis of pituitary tumors.     

D-2 dopaminergic agonists and adenosine 3',5'-monophosphate directly regulate the synthesis of alpha-melanocyte-stimulating hormone-like peptides by cultured rat melanotrophs

When placed in short term (2-day) tissue culture, the melanotrophs from the intermediate lobe of the rat pituitary gland synthesize a proopiomelanocortin-like material (POMC-LM). Exposure of these cells to bromocriptine (CB 154), an agonist upon their D-2 dopamine receptor, reduces the synthesis of POMC-LM; spiroperidol, an antagonist of the D-2 receptor, prevents this effect of CB 154. Cultured melanotrophs secrete an alpha MSH-like material. The amount of this alpha MSH-like material, either stored intracellularly or secreted into the culture medium, can be quantified in a specific RIA; the material identified in this manner is designated immunoreactive alpha MSH (IR-alpha MSH). CB 154 inhibits the secretion of IR-alpha MSH from these cells. Either spiroperidol or 8-bromo-cAMP prevent this inhibitory effect of CB 154. The capacity of these cells to synthesize alpha MSH-like molecules and release them into the culture medium can be assessed by incubation in the presence of [3H]tyrosine, followed by immunoprecipitation with an antibody directed against alpha MSH. This newly synthesized immunoprecipitable material is designated immunoprecipitable alpha MSH (IP-alpha MSH) and should be distinguished from IR-alpha MSH. Both CB 154 and quinpirole, a selective D-2 agonist (but not SKF 38393, a selective D-1 agonist), inhibit the synthesis and secretion of IP-alpha MSH. YM-09151-2, a selective D-2 antagonist (but not SCH 23390, a selective D-1 antagonist), blocks the inhibitory effects of quinpirole. Several compounds affecting cAMP metabolism (cholera toxin, forskolin, 8-bromo-cAMP, and 3-isobutyl-1-methylxanthine) can also prevent the inhibitory effect of CB 154 on the synthesis of IP-alpha MSH. We conclude the following. The D-2 receptor in the intermediate lobe directly regulates the synthesis and secretion of IP-alpha MSH. cAMP can regulate either the synthesis of POMC-LM or the processing of this substance into alpha MSH-like peptides.     

Effect of solution of low pH on releases of beta-endorphin-like immunoreactivity and ACTH-like immunoreactivity from human gastric antral mucosa in vitro

The presence of beta-endorphin-like and ACTH-like immunoreactivities (beta-EpLI, and ACTH-LI, respectively) in human gastric antral mucosa and their release were studied. beta-EpLI (14.1 +/- 4.8 ng/g wet weight) and ACTH-LI (11.1 +/- 1.2 ng/g wet weight) were detected in human gastric antral mucosa. The two activities gave similar curves for inhibition of human beta-Ep and ACTH on radioimmunoassay, respectively. On gel-filtration chromatography of a gastric antral extract, three components of beta-EpLI and two components of ACTH-LI were separated. When human gastric antral mucosa was incubated with a solution of pH 4.0 or pH 2.0, the release of beta-EpLI and ACTH-LI from the mucosa into the incubation medium increased 2.3-9.8-fold. However, incubation with 20 mM glucose or 20 mM amino acids did not have any effect on the release of beta-EpLI and ACTH-LI. These results indicate that beta-EpLI and ACTH-LI present in human gastric antral mucosa are released by direct action of a solution of low pH on the gastric antral mucosa.     

Expression of cytokeratins in Helicobacter pylori -associated chronic gastritis of adult patients infected with cagA ＋ strains： An immunohistochemical study

AIM:To investigate the expression of differentcytokeratins(CKs)in gastric epithelium of adult patientswith chronic gastritis infected with Helicobacter pylori(Hpylori)cagA strains.METHODS:The expression of CK 7,8,18,19 and 20was studied immunohistochemically in antral gastricbiopsies of 84 patients.All the CKs were immunostainedin cagA H pylori gastritis(57 cases),non-H pylori gastritis(17 cases)and normal gastric mucosa(10 cases).RESULTS:In cagA H pylori gastritis,CK8 wasexpressed comparably to the normal antral mucosafrom surface epithelium to deep glands.Distributionof CK18 and CK 19 was unchanged,i.e.transmucosal,but intensity of the expression was different in foveolarregion in comparison to normal gastric mucosa.Cytokeratin 18 immunoreactivity was significantly higherin the foveolar epithelium of H pylori-positive gastritiscompared to both Hpylori-negative gastritis and controls.On the contrary,decrease in CK19 immunoreactivityoccurred in foveolar epithelium of H pylori-positive gastritis.In both normal and inflamed antral mucosawithout Hpylori infection,CK20 was expressed strongly/moderately and homogenously in surface epithelium andupper foveolar region,but in H pylori-induced gastritissignificant decrease of expression in foveolar regionwas noted.Generally,in both normal antral mucosa andH pylori-negative gastritis,expression of CK7 was notobserved,while in about half cagA H pylori-infectedpatients,moderate focal CK7 immunoreactivity of theneck and coiled gland areas was registered,especially inareas with more severe inflammatory infiltrate.CONCLUSION:Alterations in expression of CK 7,18,19 and 20 together with normal expression of CK8 occurin antral mucosa of H pylori-associated chronic gastritisin adult patients infected with cagA strains.Alterationsin different cytokeratins expression might contribute toweakening of epithelial tight junctions observed in Hpylori-infected gastric mucosa.     

Beta-endorphinlike immunoreactivity and somatostatinlike immunoreactivity in normal gastric mucosa, muscle layer, and adenocarcinoma

beta-Endorphinlike immunoreactivity and somatostatinlike immunoreactivity were detected in the mucosa and muscle layer of normal gastric antrum and corpus and in moderately differentiated adenocarcinoma derived from the antral mucosa. The concentration of beta-endorphinlike immunoreactivity in the normal gastric tissues was 4-15 pmol/g wet wt tissue; this value varied from 9.64 to 241.39 pmol/g wet wt tissue (81.38 +/- 37.82 pmol/g wet wt tissue) in adenocarcinomas. The concentration of somatostatinlike immunoreactivity was 18-25 pmol/g wet wt tissue in normal gastric mucosa, whereas it was 1-2 pmol/g wet wt tissue in adenocarcinomas. Gel exclusion chromatography of beta-endorphinlike immunoreactivity revealed two peaks corresponding to beta-endorphin and beta-lipotropin. In normal mucosa and in the whole layer of antrum, the major peak was eluted near the position of beta-lipotropin, and the minor broad peak was eluted near the position of beta-endorphin. In contrast, in adenocarcinoma, beta-endorphinlike immunoreactivity was eluted broadly at the position of beta-endorphin and the other smaller peak was at the position of beta-lipotropin. Gel exculsion chromatography of somatostatinlike immunoreactivity also showed different patterns between antral mucosa and adenocarcinoma. This study revealed the presence of the opioid peptide, beta-endorphinlike immunoreactivity, not only in normal gastric tissue but also in adenocarcinomas with highly increased concentration and different elution patterns in combination with decreased concentration of somatostatinlike immunoreactivity.     

CORTICOTROPHIN-LIKE INTERMEDIARY LOBE PEPTIDE AS A MARKER OF ALTERNATE PRO-OPIOMELANOCORTIN PROCESSING IN ACTH-PRODUCING NON-PITUITARY TUMOURS

In order to evaluate which of human (h) corticotrophin-like intermediary lobe peptide (CLIP) or h beta-melanocyte stimulating hormone5-22 (h beta MSH5-22) was the better marker of alternate pro-opiomelanocortin (POMC) processing, both peptides were simultaneously sought in the same tissue extracts from a normal human pituitary, six corticotrophic adenomas, and four non-pituitary tumours responsible for an ectopic ACTH syndrome. Human CLIP was detected using a combination of gel exclusion chromatography and two different radioimmunoassays (RIAs): a mid-ACTH RIA which recognized ACTH but not CLIP, and a COOH-ACTH RIA which recognized both molecules. Human beta MSH5-22 had been measured previously. Neither hCLIP nor h beta MSH5-22 were detected in the normal or tumoural pituitaries. The four non-pituitary tumours, in contrast, contained both peptides; the hCLIP and h beta MSH5-22 ratios (CLIP/CLIP + ACTH and h beta MSH5-22/h beta MSH5-22 + h gamma LPH) ranged from 40 to 94% and from 24 to 46%, respectively. In a given tissue the hCLIP ratio was always higher than the h beta MSH5-22 ratio. hCLIP is therefore the better marker of alternate POMC processing.     

Processing of the precursor to corticotropin and beta-lipotropin in humans.

The biosynthesis of human corticotropin (ACTH) was studied in organ culture of pituitary adenomas and by translating mRNA from an ectopic ACTH-producing tumor in a cell-free system. Peptides similar to human ACTH, beta-lipotropin, and the amino-terminal glycopeptide are cleaved from a common precursor with an apparent molecular weight of 35,000 on sodium dodecyl sulfate/polyacrylamide gels. The precursors synthesized in pituitary and ectopic ACTH-producing tissues are indistinguishable. The cleavage sites of the peptide chain appear to be similar to those previously deduced for murine and bovine ACTH. Immunoprecipitation studies suggest that the primary structure of the precursor peptide is similar in all three species. However, glycosylation is different in the human and murine precursors: the precursor to human ACTH appears to be glycosylated only in the amino-terminal fragment, not in the ACTH or beta-lipotropin sequences. Studies with an autopsied normal human pituitary suggest that neither normal nor adenomatous pituitary tissue glycosylates the ACTH sequence.     

Analysis of human sodium iodide symporter immunoreactivity in human exocrine glands

The human sodium iodide symporter (hNIS) is an intrinsic transmembrane protein that mediates the active transport of iodide across the basolateral membrane of thyroid follicular cells. In addition to normally functioning thyroid tissue, various extrathyroidal tissues, including salivary gland, lacrimal gland, gastric mucosa, choroid plexus, and lactating mammary gland, have been demonstrated to accumulate iodide. After cloning and molecular characterization of the sodium iodide symporter, expression of hNIS messenger ribonucleic acid has been detected in a broad range of extrathyroidal tissues using Northern blot analysis and RT-PCR. In this study we used both monoclonal and polyclonal antibodies directed against different portions of hNIS protein together with a highly sensitive immunostaining technique to assess hNIS protein expression in tissue sections derived from normal human salivary and lacrimal glands, pancreas, as well as gastric and colonic mucosa. Immunohistochemical analysis of normal human salivary and lacrimal glands revealed marked hNIS immunoreactivity in ductal cells and less intense staining of acinar cells. Further, immunostaining of gastric and colonic mucosa showed marked hNIS immunoreactivity confined to chief and parietal cells in gastric mucosa and to epithelial cells lining mucosal crypts in colonic mucosa. In normal human pancreas, hNIS immunoreactivity was located in ductal cells, exocrine parenchymal cells, and Langerhans islet cells. In conclusion, our study demonstrates the expression of hNIS protein by several human exocrine glands, suggesting that iodide transport in these glands is a specific property conferred by the expression of hNIS protein, which may serve important functions by concentrating iodine in glandular secretions.