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M Bigazzi

Publications and source records attributed to M Bigazzi.

At least 37 records · Page 2Linked to original sources
PubMed1994

Relaxin influences growth, differentiation and cell-cell adhesion of human breast-cancer cells in culture.

The effects of different concentrations of relaxin (RLX) on growth and differentiation of a human breast-cancer cell line (MCF-7) have been studied after various times of exposure. The cells were cultured for 4 and 7 days in the absence (control) and the presence of highly purified porcine RLX at concentrations of 10(-9) M and 10(-6) M. (3H)-Thymidine uptake assay was used to evaluate cell proliferation. Electron microscopy and immunocytochemistry for the cell-cell adhesion molecule E-cadherin were carried out to evaluate cell differentiation. Analysis of DNA changes associated with apoptosis was performed to clarify whether RLX induces active cell death in the MCF-7 cells. The findings obtained show that RLX, when applied at micromolar concentrations, or even at nanomolar concentrations for long exposure times, suppresses proliferation, stimulates differentiation, and enhances expression of the surface molecule E-cadherin. Growth inhibition is not accompanied by apoptosis. The results of this study show that RLX can be recognized as a novel agent active in influencing growth and differentiation of MCF-7 breast-cancer cells. When applied at appropriate concentrations and exposure times, the peptide has a growth-inhibitory action, thus reversing the growth-stimulatory effect exerted at low concentrations for short exposure times, and promotes differentiation and cell-cell adhesion. These last-mentioned properties might result in a decrease in invasiveness of breast adenocarcinoma cells.

Adenocarcinoma↗
PubMed1994

Differentiation of breast cancer cells in vitro is promoted by the concurrent influence of myoepithelial cells and relaxin.

Our previous studies showed that relaxin promotes differentiation of MCF-7 breast adenocarcinoma cells. In the current investigation, we aimed to elucidate whether the effect of the hormone is potentiated when MCF-7 cells are grown together with myoepithelial cells, thus creating a microenvironment reminiscent of the organised tissue architecture of the mammary parenchyma in vivo. The findings obtained reveal that most MCF-7 cells cultured alone have an undifferentiated, blast-like phenotype, only a minority showing a more differentiated phenotype with more organelles and rudimentary intercellular junctions. When co-cultured with myoepithelial cells more MCF-7 cells acquire ultrastructural features consistent with a more differentiated phenotype, such as a rich organellular complement, apical microvilli and intercellular junctions. When relaxin was added to the co-cultures, the ultrastructural signs of differentiation could be observed in even more MCF-7 cells and became more pronounced than in the absence of the hormone, judged by the appearance of a clear-cut polarisation of cytoplasmic organelles, an almost continuous coat of apical microvilli and numerous intracellular pseudolumina.

Adenocarcinoma↗
PubMed1994

Effects of relaxin on mast cells. In vitro and in vivo studies in rats and guinea pigs.

The results of the current study demonstrate that relaxin inhibits histamine release by mast cells. This effect is related to the peptide concentrations, and could be observed in both isolated rat serosal mast cells stimulated with compound 48/80 or calcium ionophore A 23187, and in serosal mast cells isolated from sensitized guinea pigs and challenged with the antigen. The morphological findings agree with the functional data, revealing that relaxin attenuates calcium ionophore-induced granule exocytosis by isolated rat serosal mast cells. Similar effects of relaxin have also been recognized in vivo by light microscopic and densitometric analysis of the mesenteric mast cells of rats which received the hormone intraperitoneally 20 min before local treatment of the mesentery with calcium ionophore. Moreover, evidence is provided that relaxin stimulates endogenous production of nitric oxide and attenuates the rise of intracellular Ca2+ concentration induced by calcium ionophore. The experiments with drugs capable of influencing nitric oxide production also provide indirect evidence that the inhibiting effect of relaxin on mast cell histamine release is related to an increased generation of nitric oxide. It is suggested that relaxin may have a physiological role in modulating mast cell function through the L-arginine-nitric oxide pathway.

Animals↗
PubMed1992

Relaxin influences the growth of MCF-7 breast cancer cells. Mitogenic and antimitogenic action depends on peptide concentration.

BACKGROUND: The effects of relaxin (RLX) on the human breast adenocarcinoma cell line MCF-7 have been evaluated. METHODS: The cells were maintained in culture with Dulbecco's modified Eagle's medium with 1% and 10% fetal calf serum. Highly purified porcine RLX was added at concentrations ranging between 10(-11) and 10(-6) M, and, after 96-hour incubation in the presence of the peptide, cell proliferation, intracellular cyclic adenosine monophosphate (cAMP) content, percent cycling cells, and structural and ultrastructural pattern were studied. RESULTS: The results indicate that RLX is a direct modulator of MCF-7 cell proliferation, stimulating growth at low concentrations and inhibiting growth at high concentrations. Determinations of percent cycling cells and intracellular cAMP accumulation agree with the results of the growth studies. Addition of different concentrations of 8-Br-cAMP to the culture medium results in a dose-related stimulation of MCF-7 cell proliferation. Morphologic examination shows that, in the current experiments, RLX does not induce any clear-cut signs of differentiation of MCF-7 cells in terms of activation of secretion or intracellular lipid deposition. CONCLUSION: These findings indicate that RLX should be regarded as a novel agent involved in the control of growth of human breast cancer cells.

Adenocarcinoma↗
PubMed1990

Response of the pigeon crop sac to mammotrophic hormones: comparison between relaxin and prolactin.

The effects of relaxin (RLX), a hormone that has previously been demonstrated to have mammotrophic properties, were studied in the pigeon crop sac, a well-known target organ for mammotrophic and lactogenic hormones, and compared with the effects produced by prolactin (PRL). The two hormones were injected directly over the crop at different doses and the response was evaluated after differing times of exposure. RLX causes a dose-related increase in wet and dry weights and [3H]thymidine and [3H]uridine uptake by the crop mucosa, as well as morphological changes indicating growth and differentiation of the epithelial cells similar to those occurring during physiological activation in incubation and hatching. At the doses assayed, the effects of RLX were nearly identical to those obtained following PRL in the short-term experiments, but differences in functional responses were found in the long-term experiment.

Animals↗
PubMed1989

Responsiveness of mouse parametrial fat to relaxin.

The effects of relaxin on the hypertrophy of the parametrial fat cells in ovariectomized virgin mice have been studied histologically and morphometrically. This hormone has been previously demonstrated by us to induce hypertrophy also in the adipose cells of the mouse mammary gland. This effect produced by relaxin on mammary adipocytes was greater than that due to estrogen alone and independent of pretreatment with estrogen. When insulin was given after estrogen in place of relaxin the effect was nearly the same as that following relaxin alone. On the contrary, in parametrial adipocytes under the same hormonal conditions, we found an increase in the mean diameter of 28% following estrogen alone, 57% following relaxin alone, 80% when relaxin was given after pretreatment with estrogen, and 60% when insulin was given after pretreatment with estrogen at the same dose as relaxin. These results clearly reveal that relaxin is a very active hormone in promoting lipid deposition in the parametrial adipose cells, and that such an effect attains a maximum following a pretreatment with estrogen. Moreover, these findings indicate that the parametrial fat cells can be included in the list of the targets of relaxin.

Adipose Tissue↗
PubMed1988

Relaxin: a mammotropic hormone promoting growth and differentiation of the pigeon crop sac mucosa.

The pigeon crop sac is responsive to local administration of mammotropic hormones independently of systemic hormonal influences. We showed previously in mice that relaxin promotes growth of the mammary gland only after pre-treatment with estrogen. In this study we investigated whether relaxin, locally administered, has a stimulatory effect without estrogen pre-treatment. The results of this study show that relaxin stimulates the crop sac mucosa causing changes in its gross appearance and histological modifications indicating enhanced growth and differentiation of the mucosal epithelium. The effects of relaxin are dose-related, as demonstrated by the increases of the wet and dry weights, the [3H]thymidine and [3H]uridine uptakes of the mucosa, and the histochemically detectable DNA content of the mucosal epithelium. These results strengthen the idea that relaxin should be included in the list of mammotropic hormones.

Animals↗
PubMed1988

Effects of relaxin on the microvasculature of mouse mammary gland.

The effects of RLX on the microvasculature of the mouse mammary gland are reported. RLX (pure porcine standard NIH-RXN-P1) at a dose of 3 GPU was administered subcutaneously to virgin adult mice ovariectomized 12 days before. The mammary glands were removed 18-20 h after RLX injection and their examination by light microscopy did not reveal any substantial growth-response to the hormone. Histology and morphometry indicated striking dilation of microvessels, especially capillaries, and electron microscopy revealed an increase in the micropinocytotic vesicles, thus suggesting enhanced transendothelial transport of substances. Such phenomena, which were independent of a release of granules by mast cells, may represent an important component of the mammotrophic action of RLX.

Animals↗
PubMed1987

Ultrastructural studies on white adipocyte differentiation in the mouse mammary gland following estrogen and relaxin.

White adipocyte differentiation was studied ultrastructurally in the mouse mammary gland following stimulation with 17beta-estradiol and relaxin. These hormones have been previously demonstrated by us to induce hyperplasia and hypertrophy in the adipose cells of the mouse mammary gland. Following hormone treatment new fat cells are formed around the growing ducts. In these sites there is a close relationship between blood vessel growth and adipocyte development, and stromal areas featuring embryonic fat organs can frequently be found. In the sites of adipocyte differentiation the most numerous cell types are undifferentiated mesenchymal cells and preadipocytes, while fibroblasts and macrophages are much less common. No endothelial cells or pericytes were found detaching from the blood capillary walls. There were no fibroblasts or macrophages containing intracellular lipid deposits. Actively degranulating mast cells were frequent. The above findings strongly suggest the direct origin of adipocytes from perivascular mesenchymal cells, without the intermediate stages of well-differentiated fibroblasts, macrophages, endothelial cells or pericytes. The earliest morphologically recognizable stage in adipocyte differentiation is a 'pale preadipocyte', characterized by its irregular shape due to cytoplasmic processes, clear cytoplasmic matrix, well-developed organelles (especially ribosomes and Golgi apparatus), few and small lipid droplets, numerous pinocytotic vesicles and a very thin basal lamina. The next stage in adipocyte differentiation is a 'dark preadipocyte' showing a denser cytoplasmic matrix, reduced organelles and more abundant lipid accumulations. The pinocytotic vesicles are very numerous and the enveloping basal lamina is still thin. The subsequent maturation stages are the well-known globular multivacuolated adipocyte and finally the mature univacuolated, signet-ring, white adipocyte.

Adipose Tissue↗
PubMed1986

The effects of relaxin on the mouse mammary gland. II. The epithelium.

The study deals with the effects of relaxin (RLX) on epithelial cells of the mammary ducts in ovariectomized virgin mice, evaluated by light and electron microscopy. One microgram (3 GPU) pure porcine RLX (NIH-RXN-P1) was administered either alone or after pretreatment with estrogen. The possibility of a non specific binding of RLX to insulin receptors on the mammary epithelial cells was excluded by comparing the effects of the administration of the two hormones at the same doses. Our findings indicate that RLX greatly enhances the growth of the mammary duct epithelial cells, as demonstrated by the extensive branching and elongation of the ducts, and by the rather frequent occurrence of mitoses in the epithelial cell precursors and of the intermediate stages of their differentiation into mature duct cells. Three GPU RLX, administered alone, had only an inconstant and slight effect on the epithelial cell growth, a priming dose with estrogen being necessary to obtain the highest levels of duct growth. Moreover the treatment with 1 microgram of insulin for the same time showed a very inconstant and lesser effect in comparison to RLX. We did not find any evidence of alveolar maturation and milk secretion in the RLX-treated mice. The recognition of a stimulatory role of RLX on the proliferation and growth of the mammary duct epithelium may be of a certain importance in the understanding of hormonal control of the mammary development in physiological conditions and the genesis and growth of mammary neoplasms.

Animals↗
PubMed1986

Effects of relaxin on the mouse mammary gland. III. The fat pad.

The effects of relaxin on the growth of the mammary fat cells of ovariectomized virgin mice have been studied histologically and morphometrically. To characterize the effects of relaxin and investigate a possible synergism in promoting growth of the mammary fat pad, some animals were treated with other mammotrophic hormones, namely estrogen and insulin. The data obtained after 18-20 h of relaxin treatment suggest that this hormone induces hypertrophy and hyperplasia of adipose cells. The degree of hypertrophy is the same if relaxin is given either alone or after estrogen priming. The action of estrogen seems to be obligatory to obtain fat cell hyperplasia. Indeed, a de novo formation of fat cells occurs in all animals treated with estrogen, either alone or in association with relaxin or insulin. However, the maximum degree of adipose cell hyperplasia was attained only when relaxin followed a pretreatment with estrogen, thus suggesting a synergistic action of these two hormones in promoting the overall growth of the mammary fat pad. These findings follow the observation that relaxin stimulates the proliferation and differentiation of epithelial and myoepithelial cells of the duct system and strongly support the idea that relaxin may be regarded as a trophic hormone for the parenchymal and stromal components of the mammary gland.

Adipose Tissue↗
PubMed1986

The local administration of relaxin induces changes in the microcirculation of the rat mesocaecum.

The clinical improvement of Raynaud's disease during pregnancy has been attributed to the increased relaxin (RLX) level in blood. Therefore we investigated the effect of topical porcine RLX (NIH-RXN-Pl) on the microcirculation of the mesocaecum of Wistar male rats, under direct microscope observation as judged by two observers. The hormone was applied locally to avoid systemic interferences either alone or after norepinephrine (NE) and promethazine (PM). The drugs were coded and the results were recorded independently by two observers. Porcine RLX induced rapid dilatation of the veins of the rat mesocaecum in a dose-related manner. The arteriolas and capillary flows were unchanged, while the venular flow was progressively reduced. The observed effects were sustained and disappeared with tissue wash-out. The RLX effects were reversed by addition of NE; conversely high doses of RLX were able to oppose the NE and PM vasospasm. We conclude that the local administration of RLX influences the microcirculation, possibly through an action on the smooth muscle of the venulae. The effects seems antagonistic with those of NE and PM.

Administration, Topical↗
PubMed1985

Effects of relaxin on the mouse mammary gland. I. The myoepithelial cells.

Myoepithelial cells (MEC) were studied in the mammary gland of ovariectomized virgin mice without any hormonal treatment and following the administration of either estrogen or estrogen plus relaxin (either purified porcine relaxin standard or partially purified human relaxin extracted from decidua). Changes in MEC lineage were observed at both the light and electron microscopic levels in the hormonally treated animals as compared with the untreated controls. After 7 days of estrogen administration, there was a moderate elongation and branching of ducts. At the growing tips and buds undifferentiated precursors and promyoepithelial cells at various stages of their differentiation were seen with some frequency. After relaxin administration (18-20 hrs) to mice pre-treated with estrogen, branching and elongation of ducts were greatly increased as compared to mice treated with estrogen alone. At the growing points the ducts showed multi-layered walls and undifferentiated precursors were quite frequently found with some mitotic figures. Moreover several promyoepithelial cells at various stages of differentiation were observed. These findings, which were similar after administration of the two different relaxin preparations, indicate a high rate of proliferation and differentiation of MEC in these experimental conditions and hence suggest that relaxin greatly enhances the de novo formation of MEC. A stimulatory effect of relaxin on MEC growth is discussed in terms of a possible role of this hormone in the genesis of benign and malignant neoplasms of the mammary gland, in which MEC proliferation can be recognized.

Animals↗
PubMed1984

Morphological changes induced in mouse mammary gland by porcine and human relaxin.

The effects of pure porcine relaxin and of human decidual extracts with relaxin-like activity on the mammary gland of virgin mice primed with estrogen have been studied by the light microscope. Porcine relaxin enhanced the changes induced by estrogen alone; the effect was different in the various mammary tissues. In the stroma, relaxin only slightly increased the loosening of connective tissue, the extent of the adipose tissue and of the capillary bed, as well as the degranulation of the mast cells. The changes in the parenchyma, such as elongation and branching of ducts, are strikingly enhanced. Moreover, relaxin seems to promote differentiation of the cells forming the walls of distal ducts, and of the myoepithelial cells. Tissue extracts of human decidua with relaxin-like activity induce changes in the mammary gland similar to those due to porcine relaxin. Such data indicate that relaxin synergizes with estrogen to cause growth of ducts of the mammary gland and that tissue extracts of human decidua have a similar effect, thus providing further evidence that decidua may be a source of relaxin in humans.

Adipose Tissue↗
PubMed1981

Prolactin and relaxin: antagonism on the spontaneous motility of the uterus.

Prolactin (PRL) and Relaxin (RXL) are present in human decidua at term. In previous experiments we observed that the inhibition of spontaneous uterine contractions produced by decidual RLX was masked or absent if the samples were contaminated with PRL. The present study reports the effect of purified human PRL and of sera from hyperprolactinemic patients on the motility of the uterus in vitro. Also, we studied the effect of RLX on the uterus after exposure to PRL. High-PRL sera and purified human PRL produced prompt increases in the frequency and the amplitude of the spontaneous contractions of the rat uterus. PRL antagonized RLX both when the uterus was exposed first to RLX and then to PRL and when it was exposed first to PRL and then to RLX.

Animals↗