scholarly journals Prolactin Suppression of Gonadotropin-Releasing Hormone Initiation of Mammary Gland Involution in Female Rats

Endocrinology ◽  
2016 ◽  
Vol 157 (7) ◽  
pp. 2750-2758 ◽  
Author(s):  
Duangjai Rieanrakwong ◽  
Titaree Laoharatchatathanin ◽  
Ryota Terashima ◽  
Tomohiro Yonezawa ◽  
Shiro Kurusu ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Mast Cells ◽  
Epithelial Cells ◽  
Female Rats ◽  
Local Administration ◽  
Boyden Chamber ◽  
Plasma Prolactin ◽  
Mammary Gland Involution ◽  
Prolactin Suppression ◽  
Mammary Tissues

It has been demonstrated that mammary gland involution after lactation is initiated by accumulation of milk in alveoli after weaning. Here, we report that involution is also dependent on mammary GnRH expression that is suppressed by PRL during lactation. Reduction of plasma prolactin (PRL) by the withdrawal of suckling stimuli increased GnRH and annexin A5 (ANXA5) expression in the mammary tissues after lactation with augmentation of epithelial apoptosis. Intramammary injection of a GnRH antagonist suppressed ANXA5 expression and apoptosis of epithelial cells after forcible weaning at midlactation, whereas local administration of GnRH agonist (GnRHa) caused apoptosis of epithelial cells with ANXA5 augmentation in lactating rats. The latter treatment also decreased mammary weight, milk production, and casein accumulation. Mammary mast cells were strongly immunopositive for GnRH and the number increased in the mammary tissues after weaning. GnRHa was shown to be a chemoattractant for mast cells by mammary local administration of GnRHa and Boyden chamber assay. PRL suppressed the mammary expression of both ANXA5 and GnRH mRNA. It also decreased mast cell numbers in the gland after lactation. These results are the first to demonstrate that GnRH, synthesized locally in the mammary tissues, is required for mammary involution after lactation. GnRH is also suggested to introduce mast cells into the regressing mammary gland and would be in favor of tissue remodeling. The suppression of these processes by PRL is a novel physiological function of PRL.

scholarly journals Prototheca zopfiiGenotype II induces mitochondrial apoptosis in models of bovine mastitis

2019 ◽  
Author(s):  
Muhammad Shahid ◽  
Eduardo R. Cobo ◽  
Liben Chen ◽  
Paloma A. Cavalcante ◽  
Herman W. Barkema ◽  
...  
Keyword(s):  
Cell Death ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Bovine Mastitis ◽  
Mammary Epithelial ◽  
Mitochondrial Apoptosis ◽  
Prototheca Zopfii ◽  
Severe Inflammation ◽  
Mammary Tissues

AbstractPrototheca zopfiiis an alga increasingly isolated from bovine mastitis. Of the two genotypes ofP. zopfii(genotype I and II (GT-I and II)),P. zopfiiGT-II is the genotype associated with acute mastitis and decreased milk production by unknown mechanisms. The objective was to determine inflammatory and apoptotic roles ofP. zopfiiGT-II in cultured mammary epithelial cells (from cattle and mice) and murine macrophages and using a murine model of mastitis.Prototheca zopfiiGT-II (but not GT-I) invaded bovine and murine mammary epithelial cells (MECs) and induced apoptosis, as determined by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling assay. ThisP. zopfiiGT-II driven apoptosis corresponded to mitochondrial pathways; mitochondrial transmembrane resistance (ΔΨm) was altered and modulation of mitochondrion-mediated apoptosis regulating genes changed (increased transcriptionalBax, cytochrome-c andApaf-1and downregulatedBcl-2), whereas caspase-9 and -3 expression increased. Apoptotic effects byP. zopfiiGT-II were more pronounced in macrophages compared to MECs. In a murine mammary infection model,P. zopfiiGT-II replicated in the mammary gland and caused severe inflammation with infiltration of macrophages and neutrophils and upregulation of pro-inflammatory genes (TNF-α,IL-1βandCxcl-1) and also apoptosis of epithelial cells. Thus, we concludedP. zopfiiGT-II is a mastitis-causing pathogen that triggers severe inflammation and also mitochondrial apoptosis.Author summaryBovine mastitis (inflammation of the udder) reduces milk production and quality, causing huge economic losses in the dairy industry worldwide. Although the algaPrototheca zopfiiis a major cause of mastitis in dairy cows, mechanisms by which it damages mammary tissues are not well known. Here, we used cell cultures and a mouse model of mastitis to determine howProtothecacaused inflammation and cell death in mammary tissues.Protothecainvaded mammary gland cells, from cattle and mice, as well as macrophages (white cells that take up and kill pathogens) and caused cell death by interfering with mitochondria. Furthermore,Protothecacauses severe inflammation and tissue damage when injected into the mammary glands of mice. Although there are two genotypes ofP. zopfii, only genotype II causes tissue damage, whereas gentotype I, common in farm environments, does not damage mammary tissues. SinceP. zopfiiis an alga and not a bacterium, antibiotic treatments, frequently used to treat mastitis in cattle, are not effective against this organism. Understanding howP. zopfiidamages mammary tissue and causes mastitis is important new knowledge to promote future development of evidence-based approaches to prevent and treat mammary gland infections with this organism.

ULTRASTRUCTURAL CHANGES ACCOMPANYING INVOLUTION OF THE MAMMARY GLAND IN THE ALBINO RAT

1971 ◽  
Vol 51 (1) ◽  
pp. 127-135 ◽  
Author(s):  
R. C. RICHARDS ◽  
G. K. BENSON
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Alveolar Epithelial Cells ◽  
Female Rats ◽  
Ultrastructural Changes ◽  
Albino Rat ◽  
Alveolar Epithelial ◽  
Cellular Debris ◽  
Progressive Necrosis ◽  
Removal Of Fat

SUMMARY Adult female rats undergoing their first lactation were experimentally weaned by removing their pups on day 4 of lactation. The initial phase of mammary gland involution began with the removal of protein granules from the milk by digestion in large stasis vacuoles in the alveolar epithelial cells. Later stages involved a progressive necrosis of the epithelial cells by auto-phagocytosis. Removal of fat droplets and cellular debris occurred at this time and was accomplished by macrophage-like cells. Finally, epithelial cells were detached from the basement membrane and were found, in varying stages of degeneration, lying free in the lumina of the alveoli.

scholarly journals Immune Cells and Immunoglobulin Expression in the Mammary Gland Tumors of Dog

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1189
Author(s):  
Alessandra Sfacteria ◽  
Ettore Napoli ◽  
Claudia Rifici ◽  
Daria Commisso ◽  
Giada Giambrone ◽  
...  
Keyword(s):  
Mammary Gland ◽  
B Cells ◽  
Mast Cells ◽  
Epithelial Cells ◽  
Immune Cells ◽  
Therapeutic Potential ◽  
Inflammatory Cells ◽  
Mammary Gland Tumors ◽  
Peritumoral Stroma ◽  
Canine Mammary Gland

Inflammatory cells have a role in tumor progression and have prognostic and therapeutic potential. The immunohistochemical expression for Mast Cell Tryptase, Macrophage Marker, CD79a, IgA, IgM and IgG on 43 cases of canine mammary gland lesions was analyzed. In hyperplasia, a few B cells (BCs) and Tumor-Associated Macrophages (TAMs) were observed, while the number of Tumor-Associated Mast Cells (TAMCs) was the highest. In the peritumoral stroma of malignant lesions, low number of TAMCs and a high number of TAMAs and BCs were present. Immune cells of each type were always lower in the intratumoral than peritumoral stroma. Positivity to CD79a was also detected in the epithelial cells of simple and micropapillay carcinomas. Immunoglobulin reactivity was mainly located in the epithelial cells where an intense positivity to IgA and IgG and a weak positivity for IgM were detectable. On the basis of our preliminary results and literature data, we suggest that such cells and molecules could be directly involved in the biology of canine mammary gland tumors. In breast cancer, stromal inflammatory cells and cancer derived immunoglobulins have been correlated with the progression, malignancy and poor prognosis of the tumor. The results herein reported show that the dog’s mammary gland epithelium also expresses immunoglobulins, and they mostly show a direct relationship with the infiltration of macrophages. In addition, this study shows that the infiltration of mast cells, B-cells and macrophages varies depending on the degree of malignancy of neoplasia.

scholarly journals Two distinct phases of apoptosis in mammary gland involution: proteinase-independent and -dependent pathways

Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 181-193 ◽  
Author(s):  
L.R. Lund ◽  
J. Romer ◽  
N. Thomasset ◽  
H. Solberg ◽  
C. Pyke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
Tissue Remodeling ◽  
Apoptotic Cells ◽  
Gelatinase A ◽  
Casein Gene ◽  
Mammary Gland Involution ◽  
Beta Casein

Postlactational involution of the mammary gland is characterized by two distinct physiological events: apoptosis of the secretory, epithelial cells undergoing programmed cell death, and proteolytic degradation of the mammary gland basement membrane. We examined the spatial and temporal patterns of apoptotic cells in relation to those of proteinases during involution of the BALB/c mouse mammary gland. Apoptosis was almost absent during lactation but became evident at day 2 of involution, when beta-casein gene expression was still high. Apoptotic cells were then seen at least up to day 8 of involution, when beta-casein gene expression was being extinguished. Expression of sulfated glycoprotein-2 (SGP-2), interleukin-1 beta converting enzyme (ICE) and tissue inhibitor of metalloproteinases-1 was upregulated at day 2, when apoptotic cells were seen initially. Expression of the matrix metalloproteinases gelatinase A and stromelysin-1 and the serine proteinase urokinase-type plasminogen activator, which was low during lactation, was strongly upregulated in parallel starting at day 4 after weaning, coinciding with start of the collapse of the lobulo-alveolar structures and the intensive tissue remodeling in involution. The major sites of mRNA synthesis for these proteinases were fibroblast-like cells in the periductal stroma and stromal cells surrounding the collapsed alveoli, suggesting that the degradative phase of involution is due to a specialized mesenchymal-epithelial interaction. To elucidate the functional role of these proteinases during involution, at the onset of weaning we treated mice systemically with the glucocorticoid hydrocortisone, which is known to inhibit mammary gland involution. Although the initial wave of apoptotic cells appeared in the lumina of the gland, the dramatic regression and tissue remodeling usually evident by day 5 was substantially inhibited by systemic treatment with hydrocortisone. mRNA and protein for gelatinase A, stromelysin-1 and uPA were weakly induced, if at all, in hydrocortisone-treated mice. Furthermore, mRNA for membrane-type matrix metalloproteinase decreased after hydrocortisone treatment and paralleled the almost complete inhibition of activation of latent gelatinase A. Concomitantly, the gland filled with an overabundance of milk. Our data support the hypothesis that there are at least two distinct phases of involution: an initial phase, characterized by induction of the apoptosis-associated genes SGP-2 and ICE and apoptosis of fully differentiated mammary epithelial cells without visible degradation of the extracellular matrix, and a second phase, characterized by extracellular matrix remodeling and altered mesenchymal-epithelial interactions, followed by apoptosis of cells that are losing differentiated functions.

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