Thyroidal modulation of androgenic expression in mice submandibular gland

We investigated the influence of testes and thyroid gland on the maintenance of biochemical parameters and of [3H]R1881 binding sites of adult mice submandibular gland (SMG). Castration (Cx) performed at beginning of puberty prevented sex-dependent SMG development without interfering with maximal androgen binding capacity. Thyroidectomy (Tx) had strong effects on SMG, mainly by lowering the number of androgen binding sites. All alterations could be fully reverted after treatment with testosterone (5 mg/animal, single dose) or with thyroxine (T4, 250 micrograms/animal per day during 5 days). The effects of Cx on SMG could be reverted by therapy with testosterone, T4, or with both hormones (testosterone + T4) in a non-synergistic fashion. It is shown the importance of thyroidal activity on the physiological maintenance of androgen receptors in the murine SMG; the role played by thyroid gland seems to be essential for the full expression of the androgen-dependent SMG activity in adult mice.     

Global analysis of gene expression profiles in the submandibular salivary gland of klotho knockout mice

Salivary dysfunction commonly occurs in many older adults and is considered a physiological phenomenon. However, the genetic changes in salivary glands during aging have not been characterized. The present study analyzed the gene expression profile in salivary glands from accelerated aging klotho deficient mice (klotho?/?, 4 weeks old). Microarray analysis showed that 195 genes were differentially expressed (z‐score > 2 in two independent arrays) in klotho null mice compared to wild‐type mice. Importantly, alpha2‐Na⁺/K⁺‐ATPase (Atp1a2), Ca²⁺‐ATPase (Atp2a1), epidermal growth factor (EGF), and nerve growth factor (NGF), which have been suggested to be regulators of submandibular salivary gland function, were significantly decreased. When a network was constructed from the differentially expressed genes, proliferator‐activated receptor‐γ (PPAR γ), which regulates energy homeostasis and insulin sensitivity, was located at the core of the network. In addition, the expression of genes proposed to regulate various PPAR γ‐related cellular pathways, such as Klk1b26, Egfbp2, Cox8b, Gpx3, Fabp3, EGF, and NGFβ, was altered in the submandibular salivary glands of klotho?/? mice. Our results may provide clues for the identification of novel genes involved in salivary gland dysfunction. Further characterization of these differentially expressed genes will be useful in elucidating the genetic basis of aging‐related changes in the submandibular salivary gland.

     

Proline-rich-protein promoters direct LacZ expression to the granular convoluted tubular cells of the submandibular gland in adult transgenic mice

The ability of two mouse PRP gene promoters to direct the expression of the bacterial lacZ reporter gene was tested in transgenic mice. Transgenes A1-lacZ and C1-lacZ consisted of 8.2 kb A1 and 7.8 kb C1 PRP promoters respectively fused to the lacZ coding sequence. A1 and C1 are two A-type PRP genes isolated from the inbred SWR mice, which show the same gene structure and similar sequence to the closely related MP2 and M14 PRP genes previously cloned from outbred CD-1 mice. We here show that both A1-lacZ and C1-lacZ transgenes have very similar expression patterns: (1) they expressed the lacZ gene in all 14 established transgenic lines under normal (non-stimulated) conditions; (2) the expression was restricted to the granular convoluted tubular cells of the submandibular glands; (3) the expression was developmentally regulated beginning at sexual maturation and lasting to at least 1.5 years of age; and (4) expression in some lines was probably influenced by sex hormones, since higher expression was found in males than in females. A1-lacZ and C1- lacZ are the first transgenes derived from the PRP/GRP (glutamine/glutamic acid-rich protein) gene superfamily to be expressed in the granular convoluted tubular cells (with known endocrine functions), rather than in the acinar cells (with mainly exocrine functions) of the submandibular glands     

Gene expression profiling in porcine mammary gland during lactation and identification of breed-and developmental-stage-specific genes

A total of 28941 ESTs were sequenced from five 5′-directed non-normalized cDNA libraries, which were assembled into 2212 contigs and 5642 singlets using CAP3. These sequences were annotated and clustered into 6857 unique genes, 2072 of which having no functional annotations were considered as novel genes. These genes were further classified into Gene Ontology categories. By comparing the expression profiles, we identified some breed-and developmental-stage-specific gene groups. These genes may be relative to reproductive performance or play important roles in milk synthesis, secretion and mammary involution. The unknown EST sequences and expression profiles at different developmental stages and breeds are very important resources for further research.     

Gene expression profiling in porcine mammary gland during lactation and identification of breed-and developmental-stage-specific genes

The mammary gland provides an excellent system to study questions pertaining to organogenesis, cell differentiation and oncogenesis. Intensive efforts have been made to understand the development of the mammary gland, particularly in terms of lactogenesis…     

Gene expression profiling during gland morphogenesis of a mutant and a glandless upland cotton

To identify genes involved in pigment gland morphogenesis in cotton, gene expression was profiled using genechip (Affymetrix) during pigment gland morphogenesis in cotton variety Xiangmian-18, which has glandless seeds but glanded plants, and a glandless line, N5. The results showed that 303 genes were differentially expressed by a factor greater than two during gland morphogenesis; 59% (180) of these genes shared similarity with known genes in GenBank. These genes play roles in defense response, response to oxidative stress, peroxidase activity, and other metabolic pathways. KOBAS (KEGG Orthology-Based Annotation System) indicate that these genes are involved in 68 biochemical pathways. These findings suggest that the related defense response, gossypol biosynthesis pathway and other complex regulation may be associated with pigment gland morphogenesis in cotton. The results may provide a basis for further study and serve as a guide for related research.     

Species specificity of cytokeratin polypeptide expression in the submandibular gland.

Using nine monospecific and seven polyspecific monoclonal antibodies (MoAbs) against cytokeratin (CK), we immunohistochemically studied the species specificity of CK localization in human, rat, mouse, hamster and guinea pig submandibular glands (SMGs). All species showed different staining patterns with various degrees of intensity. The pattern of immunostaining was broadly classified into three groups. Group I showed positive reactivity to the rodent salivary gland, but not to human SMGs (6B10 and 34betaE12). Group 2 showed the reverse staining pattern (M20, A53-B/A2 and Ks19.1). Group 3, for which almost all species were positive, showed interspecific diversity in the staining pattern (CY-90, K8.12, K8.13, C-11 and KH-1). Species specificity of CK should always be taken into consideration when immunohistochemically examining CK expression during development or during carcinogenesis in rodents.     

Gene expression profiles of mouse submandibular gland development: FGFR1 regulates branching morphogenesis in vitro through BMP- and FGF-dependent mechanisms

Analyses of gene expression profiles at five different stages of mouse submandibular salivary gland development provide insight into gland organogenesis and identify genes that may be critical at different stages. Genes with similar expression profiles were clustered, and RT-PCR was used to confirm the developmental changes. We focused on fibroblast growth factor receptor 1 (FGFR1), as its expression is highest early in gland development. We extended our array results and analyzed the developmental expression patterns of other FGFR and FGF isoforms. The functional significance of FGFR1 was confirmed by submandibular gland organ culture. Antisense oligonucleotides decreased expression of FGFR1 and reduced branching morphogenesis of the glands. Inhibiting FGFR1 signaling with SU5402, a FGFR1 tyrosine kinase inhibitor, reduced branching morphogenesis. SU5402 treatment decreased cell proliferation but did not increase apoptosis. Fgfr, Fgf and Bmp gene expression was localized to either the mesenchyme or the epithelium by PCR, and then measured over time by real time PCR after SU5402 treatment. FGFR1 signaling regulates Fgfr1, Fgf1, Fgf3 and Bmp7 expression and indirectly regulates Fgf7, Fgf10 and Bmp4. Exogenous FGFs and BMPs added to glands in culture reveal distinct effects on gland morphology. Glands cultured with SU5402 were then rescued with exogenous BMP7, FGF7 or FGF10. Taken together, our results suggest specific FGFs and BMPs play reciprocal roles in regulating branching morphogenesis and FGFR1 signaling plays a central role by regulating both FGF and BMP expression.