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Revista Da Associacao Medica Brasileira... Jun 2021To assess the impact of the metoclopramide-induced hyperprolactinemia in cellular death and proliferation in the harderian gland of female mice.
OBJECTIVE
To assess the impact of the metoclopramide-induced hyperprolactinemia in cellular death and proliferation in the harderian gland of female mice.
METHODS
Twenty female mice were divided into two groups of 10 animals each and treated: 0.2 mL of saline solution (controls, Ctr) and 200 µg of metoclopramide (experimental, hyperprolactinemia), both for 50 consecutive days and at 12:00 a.m. On the 50th day, the female were euthanized, and the harderian glands were removed and processed for immunohistochemistry for detected ki67 and TUNEL method. Data were statistically analyzed by unpaired Student's t test (p<0.05).
RESULTS
The harderian gland of the hyperprolactinemia group showed increase in the immunoexpression of Ki67 and TUNEL compared to the Ctr group (p<0.05), and there was no significant difference in the amount of porphyrin in the HPrl group compared to the Ctr group.
CONCLUSION
The hyperprolactinemia led to increased cell death in the acini the harderian gland and cell proliferation in the stroma glandular, fact that suggesting a reduction process of cellular activity and fibrosis, which suggests impairment in the functioning of the lacrimal harderian.
Topics: Animals; Cell Proliferation; Female; Harderian Gland; Hyperprolactinemia; Lacrimal Apparatus; Mice; Porphyrins
PubMed: 34550251
DOI: 10.1590/1806-9282.20200737 -
Frontiers in Physiology 2020Photoperiod is an important factor of mammalian seasonal rhythm. The Harderian gland (HG) appears to act as a "standby" structure of the retinal-pineal axis, mediating...
Photoperiod is an important factor of mammalian seasonal rhythm. The Harderian gland (HG) appears to act as a "standby" structure of the retinal-pineal axis, mediating light signals and neuroendocrine regulation ; however, the effect of photoperiod on the HG is not clear. Here, we studied morphological differences in the HG of female striped dwarf hamsters (), a small mammal that experiences an annual rhythm, under different photoperiods (i.e., SP, short photoperiod; MP, moderate photoperiod; LP, long photoperiod), and further investigated the molecular mechanisms related to these morphological differences. Results showed that body weight, carcass weight, and HG weight were higher in the SP and LP groups than that in the MP group. Protein expression of hydroxyindole-o-methyltransferase, a key enzyme in melatonin synthesis, was higher in the SP group than in the other two groups. Somatostatin showed highest expression in the LP group. Furthermore, comparison of changes in the HG ultrastructure demonstrated autolysosome formation in the SP group. Protein aggregation and mRNA expression of LC3 and protein expression of LC3II/LC3I were higher in the SP group than in the MP group, indicating elevated autophagy under SP. Chromatin agglutination and mitochondrial damage were observed and bax/bcl2 and cytochrome C expression increased at the protein and mRNA levels in the SP and LP groups, suggesting increased apoptosis. Protein expression of dynamin-related protein 1 and mitochondrial fission factor (Mff) were highest in the SP group, suggesting elevated mitochondrial fission. Protein expression levels of adenosine triphosphate (ATP) synthase and citrate synthase were lower in the LP group than in the SP and MP groups. These results indicated that autophagy and apoptosis imbalance under SP and LP conditions may have led to HG weight loss and up-regulation of mitochondrial apoptosis may have weakened mitochondrial function under LP conditions. Finally, melatonin synthesis appeared to be positively correlated with the time hamsters entered darkness.
PubMed: 32435203
DOI: 10.3389/fphys.2020.00408 -
Comparative Medicine Dec 2022A Cancer Rainbow mouse line that expresses 3 fluorescently labeled isoforms of the tumor-driver gene (HER2BOW) was developed recently for the study of tumorigenesis in...
A Cancer Rainbow mouse line that expresses 3 fluorescently labeled isoforms of the tumor-driver gene (HER2BOW) was developed recently for the study of tumorigenesis in the mammary gland. The expression of 1 of the 3 HER2 isoforms in HER2BOW mice is induced through the Cre/ system. However, in addition to developing palpable mammary tumors, HER2BOW mice developed orbital tumors, specifically of the Harderian gland. Mice were euthanized, and histopathologic examination of the Harderian gland tumors was performed. Tumors were characterized by adenomatous hyperplasia to multinodular adenomas of the Harderian gland. Fluorescent imaging of the Harderian gland tissue confirmed the expression of HER2 in the tumors. Here we discuss monitoring and palliative approaches to allow attainment of humane experimental endpoints of mammary tumor growth in this mouse line. We describe a range of interventions, including close monitoring, topical palliative care, and surgical bilateral enucleation. Based on our data and previous reports in the literature, the overexpression of HER2 in Harderian gland tissue and subsequent tumor formation likely was driven by MMTV-Cre expression in the Harderian gland.
Topics: Mice; Animals; Mice, Transgenic; Harderian Gland; Mammary Neoplasms, Animal
PubMed: 36744508
DOI: 10.30802/AALAS-CM-22-000061 -
Comptes Rendus Biologies Mar 2018The Harderian gland (HG) of the rat (Rattus norvegicus) secretes copious amounts of lipids, such as cholesterol. Here we report a study of the expressions of the StAR...
The Harderian gland (HG) of the rat (Rattus norvegicus) secretes copious amounts of lipids, such as cholesterol. Here we report a study of the expressions of the StAR protein and key steroidogenic enzymes in the HG of male and female rats. The objective of the present investigation was to ascertain (a) whether the rat HG is involved in steroid production starting with cholesterol, and (b) whether the pattern of gene and protein expressions together with the enzymatic activities display sexual dimorphism. The results demonstrate, for the first time, the expression of StAR gene and protein, and Cyp11a1, Hsd3b1, Hsd17b3, Srd5a1, Srd5a2 and Cyp19a1 genes in the rat HG. StAR mRNA and protein expressions were much greater in males than in females. Immunohistochemical analysis demonstrated a non-homogeneous StAR distribution among glandular cells. Hsd17b3 and Cyp19a1 mRNA levels were higher in males than in females, whereas Srd5a1 mRNA levels were higher in females than in males. No significant differences were observed in mRNA levels of Cyp11a1, Hsd3b1 and Srd5a2 between sexes. Furthermore, the in vitro experiments demonstrated a higher 5α-reductase activity in the female as compared to the male HG vice versa a higher P450 aro activity in males as compared to females. These results suggest that the Harderian gland can be classified as a steroidogenic tissue because it synthesizes cholesterol, expresses StAR and steroidogenic enzymes involved in both androgen and estrogen synthesis. The dimorphic expression and activity of the steroidogenic enzymes may suggest sex-specific hormonal effects into the HG physiology.
Topics: Androgens; Animals; Enzymes; Female; Gene Expression Regulation; Harderian Gland; Lipogenesis; Male; Phosphoproteins; RNA, Messenger; Rats; Sex Characteristics
PubMed: 29534958
DOI: 10.1016/j.crvi.2018.02.001 -
Journal of Anatomy Aug 1994The harderian gland was first described in 1694 by Johann Jacob Harder (1656-1711). It occurs in most terrestrial vertebrates and is located within the orbit where, in... (Review)
Review
The harderian gland was first described in 1694 by Johann Jacob Harder (1656-1711). It occurs in most terrestrial vertebrates and is located within the orbit where, in some species, it is the largest structure. It may be compound tubular or compound tubuloalveolar, and its secretory duct is usually morphologically distinct only after leaving the substance of the gland to open on the surface of the nictitating membrane. The tubules of the gland are formed of a single layer of columnar epithelial cells surrounded by myoepithelial cells. The chief product(s) of the gland varies between different groups of vertebrates, and epithelial cells possess granules or vacuoles whose contents may be mucous, serous or lipid. In rodents, the gland synthesises lipids, porphyrins and indoles. In the case of lipid vacuoles, the gland is unusual in releasing these by an exocytotic mechanism. It is unclear whether the gland can act both as an exocrine and endocrine organ. There is control of gland structure and synthesis through a variety of humoral agents, including gonadal, thyroid and pituitary hormones; in addition there is a rich autonomic innervation and many neuropeptides have been identified. The proposed functions of the gland are remarkably diverse and include the gland being (1) a source of 'saliva', (2) a site of immune response, (3) a photoprotective organ, (4) part of a retinal-pineal axis, (5) a source of pheromones, (6) a source of thermoregulatory lipids, (7) a site of osmoregulation, and (8) a source of growth factors. The gland is discussed in terms of its embryology and phylogeny, and in relation to ecological variables. Several goals of future research are identified.
Topics: Amphibians; Animals; Birds; Harderian Gland; Mammals
PubMed: 7559104
DOI: No ID Found -
BMC Veterinary Research Sep 2022Infectious laryngotracheitis (ILT) is an economically crucial respiratory disease of poultry that affects the industry worldwide. Vaccination is the principal tool in...
Infectious laryngotracheitis (ILT) is an economically crucial respiratory disease of poultry that affects the industry worldwide. Vaccination is the principal tool in the control of the disease outbreak. In an earlier study, we comprehensively characterized the circulating strains in Egypt and identified both CEO-like and recombinant strains are dominant. Herein, we investigated the pathogenicity of two virulent strains representing the CEO-like (Sharkia_2018) and recombinant strain (Qalubia_2018). Additionally, we evaluated the efficacy of different commercial vaccines (HVT-LT, CEO, and TCO) against the two isolates in terms of the histopathological lesion scores and the viral (gC) gene load. A total of 270 White Leghorn-specific pathogen-free male chicks were divided into nine groups of 30 birds, each housed in separate isolators. Birds were distributed as follows; one group was non-vaccinated, non-challenged, and served as a negative control. Two groups were non-vaccinated and infected with the two isolates of interest and served as a positive control to test the pathogenicity. Six groups were vaccinated and challenged; two groups were vaccinated with vector vaccine at one day old. The other four groups were vaccinated with either the CEO- or TCO- vaccine (two groups each) at four weeks of age. Three weeks after vaccination, birds were infected with the virulent ILTV isolates. The larynx, trachea, and harderian gland samples were taken at 1, 3, and 7 days post-infection for histopathological lesion score and molecular detection. Notably, The recombinant strain was more virulent and pathogenic than CEO-like ILTV strains. Moreover, the TCO vaccine was less immunogenic than the vector and CEO vaccines.
Topics: Animals; Chickens; Egypt; Herpesviridae Infections; Herpesvirus 1, Gallid; Male; Poultry Diseases; Vaccine Efficacy; Vaccines, Attenuated; Viral Vaccines; Virulence
PubMed: 36163027
DOI: 10.1186/s12917-022-03458-3 -
Journal of Lipid Research Sep 2015Acyl-CoA binding protein (ACBP) is a small, ubiquitously expressed intracellular protein that binds C14-C22 acyl-CoA esters with very high affinity and specificity. We...
Acyl-CoA binding protein (ACBP) is a small, ubiquitously expressed intracellular protein that binds C14-C22 acyl-CoA esters with very high affinity and specificity. We have recently shown that targeted disruption of the Acbp gene leads to a compromised epidermal barrier and that this causes delayed adaptation to weaning, including the induction of the hepatic lipogenic and cholesterogenic gene programs. Here we show that ACBP is highly expressed in the Harderian gland, a gland that is located behind the eyeball of rodents and involved in the production of fur lipids and lipids used for lubrication of the eye lid. We show that disruption of the Acbp gene leads to a significant enlargement of this gland with hypertrophy of the acinar cells and increased de novo synthesis of monoalkyl diacylglycerol, the main lipid species produced by the gland. Mice with conditional targeting of the Acbp gene in the epidermis recapitulate this phenotype, whereas generation of an artificial epidermal barrier during gland development reverses the phenotype. Our findings indicate that the Harderian gland is activated by the compromised epidermal barrier as an adaptive and protective mechanism to overcome the barrier defect.
Topics: Acinar Cells; Animals; Cholesterol; Diazepam Binding Inhibitor; Epidermis; Harderian Gland; Lipids; Lipogenesis; Liver; Mice; Monoglycerides
PubMed: 26142722
DOI: 10.1194/jlr.M060780 -
Autophagy 2015The epithelial derived Harderian gland consists of 2 types of secretory cells. The more numerous type A cells are responsible for the secretion of lipid droplets, while...
The epithelial derived Harderian gland consists of 2 types of secretory cells. The more numerous type A cells are responsible for the secretion of lipid droplets, while type B cells produce dark granules of multilamellar bodies. The process of autophagy is constitutively active in the Harderian gland, as confirmed by our analysis of LC3 processing in GFP-LC3 transgenic mice. This process is compromised by epithelial deletion of Atg7. Morphologically, the Atg7 mutant glands are hypotrophic and degenerated, with highly vacuolated cells and pyknotic nuclei. The mutant glands accumulate lipid droplets coated with PLIN2 (perilipin 2) and contain deposits of cholesterol, ubiquitinated proteins, SQSTM1/p62 (sequestosome 1) positive aggregates and other metabolic products such as porphyrin. Immunofluorescence stainings show that distinct cells strongly aggregate both proteins and lipids. Electron microscopy of the Harderian glands reveals that its organized structure is compromised, and the presence of large intracellular lipid droplets and heterologous aggregates. We attribute the occurrence of large vacuoles to a malfunction in the formation of multilamellar bodies found in the less abundant type B Harderian gland cells. This defect causes the formation of large tertiary lysosomes of heterologous content and is accompanied by the generation of tight lamellar stacks of endoplasmic reticulum in a pseudo-crystalline form. To test the hypothesis that lipid and protein accumulation is the cause for the degeneration in autophagy-deficient Harderian glands, epithelial cells were treated with a combination of the proteasome inhibitor and free fatty acids, to induce aggregation of misfolded proteins and lipid accumulation, respectively. The results show that lipid accumulation indeed enhanced the toxicity of misfolded proteins and that this was even more pronounced in autophagy-deficient cells. Thus, we conclude autophagy controls protein and lipid catabolism and anabolism to facilitate bulk production of secretory vesicles of the Harderian gland.
Topics: Animals; Autophagy; Cell Nucleus; Epithelial Cells; Harderian Gland; Lysosomes; Mice; Proteasome Inhibitors; Vacuoles
PubMed: 25484081
DOI: 10.4161/15548627.2014.978221 -
The Anatomical Record Jul 1997The Harderian gland is an orbital feature found in most terrestrial vertebrates. Although there have been several reports on the structure of the squamate Harderian... (Review)
Review
BACKGROUND
The Harderian gland is an orbital feature found in most terrestrial vertebrates. Although there have been several reports on the structure of the squamate Harderian gland, there has been little recent discussion as to its potential function. This article reviews both the recent morphological observations and their implications on the potential functions of the squamate Harderian gland.
METHODS
Literature on the gross structure, histochemistry, and ultrastructure of the squamate Harderian gland and associated structures was reviewed. These observations were then used to assess morphologically the likelihood of the proposed functions.
RESULTS
A high level of morphological variation was found in the squamate Harderian gland. Three functional hypotheses, including roles in orbital lubrication, digestion, and vomerolfaction, were considered. Both morphology of the squamate Harderian gland and the presence of alternate secretory sources suggest that it is unlikely to function in orbital lubrication. There is little evidence to suggest a function in digestion. Both the presence of the connecting lacrimal apparatus and the reduced intrinsic secretory capacity of the vomeronasal organ suggest that the Harderian gland may function in vomerolfaction.
CONCLUSIONS
The most likely role of the squamate Harderian gland seems to be in vomerolfaction. Morphological variations observed in the Harderian gland may mirror the different degrees and mechanisms of vomerolfaction. Further studies, including comparative morphological, experimental, and microchemical analyses, are required to test this hypothesis.
Topics: Animals; Harderian Gland; Lacrimal Apparatus; Orbit; Reptiles; Vomeronasal Organ
PubMed: 9214546
DOI: 10.1002/(SICI)1097-0185(199707)248:3<301::AID-AR1>3.0.CO;2-S -
Investigative Ophthalmology & Visual... Sep 2015To determine the source(s) of vitamin D in tear fluid and examine the expression of the endocytic proteins and putative vitamin D transporters megalin and cubilin in...
PURPOSE
To determine the source(s) of vitamin D in tear fluid and examine the expression of the endocytic proteins and putative vitamin D transporters megalin and cubilin in lacrimal and Harderian glands.
METHODS
Wild-type, heterozygous, and vitamin D receptor (VDR) knockout C57BL/6 mice were used, with a subset of knockout mice fed a replenishment diet for some studies. Mouse lacrimal and Harderian glands from each group were used to measure megalin and cubilin by RT-PCR, Western blot, and immunohistochemistry. New Zealand white rabbits were used to collect lacrimal and accessory gland fluid for vitamin D mass spectroscopy measurements.
RESULTS
Ten-week-old knockout mice were significantly (P < 0.05) smaller than wild-type mice. Real-time PCR and Western blot showed decreased expression of megalin and cubilin in select VDR knockout mouse groups. Immunohistochemistry showed apical duct cell megalin staining and weaker megalin staining in VDR knockout mice compared with controls. Vitamin D2 was more prevalent in rabbit lacrimal and accessory gland fluid than vitamin D3, and greater amounts of Vitamin D2 were found in in tear fluid obtained directly from lacrimal and accessory glands as compared with plasma concentrations.
CONCLUSIONS
This is the first study to demonstrate the presence of megalin and cubilin in lacrimal and accessory glands responsible for producing tear fluid. The results strengthen the hypothesis that megalin and cubilin are likely involved in the secretory pathway of vitamin D into tear fluid by the duct cells.
Topics: Animals; Blotting, Western; Disease Models, Animal; Harderian Gland; Lacrimal Apparatus; Low Density Lipoprotein Receptor-Related Protein-2; Mass Spectrometry; Mice; Mice, Inbred C57BL; Mice, Knockout; Rabbits; Receptors, Calcitriol; Receptors, Cell Surface; Tears; Vitamin D
PubMed: 26348637
DOI: 10.1167/iovs.15-17177