Progesterone metabolism by major salivary glands of rat--I. Submandibular and sublingual glands

The metabolism of progesterone by the submandibular and sublingual salivary glands of female (nonpregnant and pregnant) and male rats was studied. The metabolism was in both sexes significantly greater in submandibular than in sublingual glands. Sex differences were not seen in sublingual glands but less metabolism was found in homogenates and microsomal fractions of female (nonpregnant and pregnant) submandibular glands compared to that of males. The metabolism did not differ between pregnant and nonpregnant female rats. The metabolites were mainly 5 alpha-pregnane-compounds. On the basis of the metabolites identified it can be concluded that rat submandibular and sublingual glands contain at least 3 alpha-, 3 beta-, 20 alpha- and 20 beta-hydroxysteroid dehydrogenase, 5 alpha- and 5 beta-steroid hydrogenase and 17 alpha-steroid hydroxylase activity. 5 alpha-steroid hydrogenase activity was significantly higher in all preparations of male submandibular glands than in females. In sublingual glands some enzyme activities showed pregnancy-related decreased.     

Distinct expression of calnexin in major human salivary glands

Calnexin (Cnx) has been characterized as a membrane-bound protein that transiently interacts in a unique chaperone system with newly synthesized glycoproteins in order to allow the establishment of their proper tertiary and, in most cases, quarternary structures. The aim of the study was to identify and to locate the expression of Cnx in the three major salivary glands of humans by different methods. Strong expression of Cnx protein and mRNA were generally found in serous salivary secretory units. With regard to mucous secretory units, expression of Cnx was only detectable at a low level in mucous acinar cells of sublingual glands, but not of submandibular glands. Expression of Cnx was always preserved in the surface epithelium of intralobar and interlobular duct segments. In addition, expression of Cnx was detected in sebaceous glands of parotid tissues, with a distribution pattern resembling that seen in sebaceous glands of the normal skin. In conclusion, production of saliva is associated with the expression of Cnx. Synthesis of molecules in mucous secretory units is not necessarily associated with a strong Cnx expression, whereas synthesis in serous secretory units apparently is. The tissue-specific Cnx expression is also paralleled by the observation that the secretions produced by the major salivary glands differ in their composition and amount.     

Fine needle aspiration biopsy cytology of major salivary glands

Fine needle aspiration biopsy of the major salivary glands was performed on 160 patients. In 146 patients with satisfactory samples, the cytologic diagnosis was correlated with clinical follow-up and histologic findings. There were 122 benign lesions, including 47 tumors. There were 24 malignant lesions, 10 of which were primary and 14 metastatic. The overall accuracy was 98%. The sensitivity of the technique was 87.5%. There was no false-positive diagnosis. There were three false-negative diagnoses due to sampling errors and inexperience during the initial period of the study. This study documents that needle aspiration biopsy cytology of the salivary glands is accurate, simple, rapid, inexpensive, well tolerated and harmless to the patient.     

Progesterone metabolism in human endometrial stromal and gland cells in culture.

Metabolism of progesterone by human endometrium has been described, but the rapidity and extent of progesterone metabolism is incompletely documented in cellular fractions of normal endometrium. Therefore, we evaluated progesterone metabolism in separated stromal and gland cells in culture obtained from normal human endometrium by thin-layer chromatography. We find that in both cell types, the most abundant metabolite is 3beta-hydroxy-5alpha-pregnan-20-one (70%), followed by 5alpha-pregnane-3,20-dione (15%), and 3alpha-hydroxy-5alpha-pregnan-20-one (10%). A small amount is metabolized to 5alpha-pregnane-3alpha/3beta,20alpha-diols and to 3beta,6alpha-dihydroxy-5alpha-pregnan-20-one. The metabolism of progesterone in cultured endometrial cells occurs rapidly; 70% of progesterone is metabolised in 8 h, and 90% by 24 h. We conclude that when in vitro experiments are conducted utilizing progesterone treatment, the rapidity and the extent of the metabolism of this steroid should be taken into account.     

Effects of acute starvation on carbohydrate metabolism in rat salivary glands.

1. Effects of acute starvation on enzymes of carbohydrate metabolism were determined in rat submandibular and parotid glands. 2. Activities of glycolytic enzymes were high in submandibular gland, but those of pentose phosphate pathway and glycogen metabolism were high in parotid gland. 3. Enzyme activities were lowered by acute starvation. Refeeding the rats with solid diet restored the enzyme activities, but with liquid diet, only partial recoveries were found in submandibular gland.     

Peptidergic innervation of the major salivary glands of the ferret

In parotid, sublingual and submandibular glands of the ferret, morphological correlates were looked for, using immunocytochemistry, to previous physiological findings showing parasympathetic "atropine-resistant" salivary secretion and neuropeptide-evoked salivation in this species. Nerve fibers storing VIP were numerous in association with acini, ducts and blood vessels, while the number of fibers storing substance P was moderate and those containing CGRP and galanin few; also the number of NPY-containing fibers was low around acini and ducts but relatively high around vessels. Sympathectomy eliminated all NPY- and almost all dopamine beta-hydroxylase-containing fibers. Parasympathectomy of the parotid gland resulted in a total loss of the VIP-containing fibers, and a profound reduction in the number of substance P- and CGRP-containing fibers.     

Chemosensory proteins, major salivary factors in caterpillar mandibular glands

Research in the field of insect-host plant interactions has indicated that constituents of insect saliva play an important role in digestion and affect host chemical defense responses. However, most efforts have focused on studying the composition and function of regurgitant or saliva produced in the labial glands. Acknowledging the need for understanding the role of the mandibular glands in herbivory, we sought to make a qualitative and semi-quantitative comparison of soluble luminal protein fractions between mandibular and labial glands of Vanessa gonerilla butterfly larvae. Amylase and lysozyme were inspected as possible major enzymatic activities in the mandibular glands aiding in pre-digestion and antimicrobial defense. Although detected, neither of these enzymatic activities was prominent in the luminal protein preparation of a particular type of gland. Proteins isolated from the glands were identified by mass spectrometry and by searching an EST-library database generated for four other nymphalid butterfly species, in addition to the public NCBI database. The identified proteins were also quantified from the data using "Quanty", an in-house program. The proteomic analysis detected chemosensory proteins as the most abundant luminal proteins in the mandibular glands. In comparison to these proteins, the relative amounts of amylase and lysozyme were much lower in both gland types. Therefore, we speculate that the primary role of the mandibular glands in Lepidopteran larvae is chemoreception which may include the detection of microorganisms on plant surfaces, host plant recognition and communication with conspecifics.     

Rescue of salivary gland function after stem cell transplantation in irradiated glands

Head and neck cancer is the fifth most common malignancy and accounts for 3% of all new cancer cases each year. Despite relatively high survival rates, the quality of life of these patients is severely compromised because of radiation-induced impairment of salivary gland function and consequential xerostomia (dry mouth syndrome). In this study, a clinically applicable method for the restoration of radiation-impaired salivary gland function using salivary gland stem cell transplantation was developed. Salivary gland cells were isolated from murine submandibular glands and cultured in vitro as salispheres, which contained cells expressing the stem cell markers Sca-1, c-Kit and Musashi-1. In vitro, the cells differentiated into salivary gland duct cells and mucin and amylase producing acinar cells. Stem cell enrichment was performed by flow cytrometric selection using c-Kit as a marker. In vitro, the cells differentiated into amylase producing acinar cells. In vivo, intra-glandular transplantation of a small number of c-Kit(+) cells resulted in long-term restoration of salivary gland morphology and function. Moreover, donor-derived stem cells could be isolated from primary recipients, cultured as secondary spheres and after re-transplantation ameliorate radiation damage. Our approach is the first proof for the potential use of stem cell transplantation to functionally rescue salivary gland deficiency.     

Distinct immunohistochemical expression of osteopontin in the adult rat major salivary glands

Osteopontin is a multifunctional protein secreted by epithelial cells of various tissues. Its expression in the adult rat major salivary glands has not yet been studied. We examined osteopontin expression by immunohistochemistry using a well characterized monoclonal antibody. Submandibular glands of young adult male rats (70–100 days old) showed specific expression in secretion granules of granular duct cells but also in cells of the striated ducts and excretory duct. In the major sublingual as well as the parotid gland expression was found solely in the duct system. In addition, a few interstitial-like cells exhibiting very strong immunostaining for osteopontin could be found in either organ. Expression could neither be seen in acinar cells nor in cells of the intercalated ducts. Moreover, in submandibular glands of more aged rats (6- to 7-month old) which show well developed granular convoluted tubules, there was almost exclusive expression of osteopontin in granular duct cells as well as in some interstitial-like cells, but barely in the striated/excretory duct system. Western blot analysis of the submandibular gland showed a specific band migrating at approximately 74 kDa, detectable at both age stages. Osteopontin secreted fom granular duct cells may influence the compostion of the saliva, e.g. thereby modulating pathways affecting sialolithiasis. Its expression in striated duct cells may also hint to roles such as cell–cell attachment or cell differentiation. The cell-specific expression detected in the rat major salivary glands differs in part from that reported in mice, human and monkey.Nicholas Obermüller and Nikolaus Gassler contributed equally to this work.     

Differential expression of laminin chains in the human major salivary gland

Laminin represents a macromolecule family. The heterotrimeric isoforms of laminin can be determined by immunohistochemical demonstration of the single chains. The laminin chain heterogeneity of the basement membrane in adult human major salivary glands was evaluated in relation to cellular differentiation of the epithelia and the stromal compartment. Monoclonal antibodies to the laminin alpha1, alpha3 (BM165) chains and epiligrin reacted with the basement membranes of serous and mucous acini and of intercalated, striated and excretory ducts. As evidenced by a double-labelling technique, the alpha2 chain showed a spatial association with the myoepithelium of the acini, whereas the ductal basement membranes containing no myoepithelial cells were negative. Almost exclusively, beta1 chain was detected in acinar basement membrane, beta2 chain whereas in ductal basement membrane. gamma2 chain is a unique chain belonging to the laminin-5 isoform. It was restricted to the ductal basement membrane. alpha1, alpha2, beta1, beta2 and gamma1 chains were detected in nerves of salivary tissue and alpha1, alpha3, beta1, beta2 and gamma1 chains and epiligrin in blood vessels. Our results indicate that the acinar ductal unit contains basement membranes with different isoforms, which relate to cell differentiation and cell function. © 1998 Chapman & Hall     

Comparative analysis of lysosomal hydrolases and natural glycoprotein substrates in the rat major salivary glands.

1. The activities of some lysosomal hydrolases and the concentrations of their natural substrates were studied in the submandibular and sublingual glands of male and female rats using biochemical procedures. 2. In sublingual gland enzyme activities and substrate concentrations show the highest values. 3. The enzyme activities appear, in general, lower and the natural substrate concentrations higher in the females with respect to males. 4. In both glands beta-galactosidase shows the highest activity and beta-glucosidase the lowest. 5. These findings suggest that metabolic turnover of glycoproteins is slower in females than in males, probably because the oestrogens control the activity of lysosomal hydrolases.