Gastone Bani

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.

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.

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 μg (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 incostant 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 μg 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.

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 o1 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.

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.

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.

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.

ULTRASTRUCTURE OF THE CELLS OF THE BOUNDARY LAYER OF SMALL VESSELS IN THE DIGESTIVE GLAND OF THE GASTROPOD PULMONATE EOBANIA VERMICULATA (MÜLLER)

SUMMARY We have described the vascular network of the digestive gland of Eobania vermiculata (Muller), with special reference to the ultrastructure of endothelial-like cells forming the capillary wall. These cells functionally correspond to elements of the normal endothelium but possess some exclusive ultrastructural features. The particular position of the cell nuclei and the relationship to the surrounding connective tissue (the loose perivascular connective tissue and interstitial vesicular cells) are shown. Irregular microvilli and pinocytosis vesicles are found on both inner and outer surfaces and oriented bundles of filaments occupy the central portion of the cytoplasm, anchoring to the plasmalemma. The hypothesis is advanced that these filaments are contractile in nature and, therefore, endothelial-like cells are retained capable of autoregulative processes, in order to adjust the calibre of the capillary lumen according to the rate of blood-tissue exchanges.

Ultrastructure of Merkel cells in the epidermis of Hyla arborea

Abstract In this ultrastructural study of the epidermis in Hyla arborea, cells quite similar to the Merkel cells already described in several vertebrate species are reported, and their relationships to the nerve terminals in intimate contact examined. Merkel cells occur rather frequently in the dorsal and ventral epidermis having features like these in other amphibian species: they contain specific, dense granules of various sizes throughout the cytoplasm, with focal accumulation near the plasma membrane areas apposed to nerve terminals. Occasionally seen are nerve endings with a peculiar fine structure suggestive of efferent nerve endings, for which a possible modulating function is proposed.

STRUCTURE OF THE FINGER-LIKE GLAND OF VAGINULA BORELLIANA (COLOSI) (GASTROPODA PULMONATA)

SUMMARY The finger-like gland of Vaginula borelliana (Colosi) (Gastropoda Pulmonata) was studied in serial sections obtained from both secretory tubules and draining pathways. There are two types of secretory tubules which differ chiefly in the staining properties of both the secretory cells and the secretion within the tubular lumina. Both tubules have in their walls two additional layers besides the secretory layer: one of smooth muscle cells and one of periluminal epithelial cells. The muscle layer, located upon the secretory cells, occupies an unusual position and probably aids in the rapid discharge of the secretion accumulated in the tubular lumen. The role of the periluminal epithelium, whose structure varies in different zones of the gland, may change according to its localization. A comparison between the histology of the finger-like gland of Vaginula and that of the multifid glands of Helix reported in the literature, reveals clear differences between these sex organs which are regarded as analo...