Possible physiological role of epidermal growth factor in the development of the mouse mammary gland during pregnancy

Epidermal growth factor stimulated cell proliferation in a primary mammary epithelial cell culture derived from mice at different stages of pregnancy. Moreover, the peptide hormone inhibited casein production induced by the synergistic actions of insulin, cortisol and prolactin. The inhibitory effect of epidermal growth factor was influenced by the gestational stages of the mammary gland. These effects of epidermal growth factor were exerted at physiological concentrations. The dual actions of epidermal growth factor on mammary cells implicate its participation in regulation of the growth and differentiation of the mammary gland during pregnancy.     

A Highly Sensitive Enzyme Immunoassay for Mouse β Nerve Growth Factor

Abstract: A sensitive two-site enzyme immunoassay system for mouse β nerve growth factor (NGF) was developed, based on the sandwiching of the antigen between anti-mouse β NGF antibody IgG coated to a polystyrene tube and anti-mouse β NGF antibody Fab'-linked β- d -galactosidase (β- d -galactoside hydrolase, EC 3.2.1.23). This method has the following advantages: (a) the procedures are simple and rapid compared to bioassay or two-site radioimmunoassay; (b) antibody Fab'-β- d -galactosidase complex is more stable than ¹²⁵I-labeled antibody; (c) purified β NGF is detectable at a concentration as low as 10 pg/ml. Our enzyme immunoassay was used to examine the levels of NGF in some tissues of mice. The submaxillary gland contained a high concentration of NGF. However, other tissues, such as the heart, brain, and skeletal muscle, and serum did not contain detectable NGF. These results support recent findings by other investigators that NGF was not found in the organs/tissues other than the submaxillary gland of mice.     

Molting in a parasitic nematode, Phocanema decipiens—VII. The mode of action of the ecdysial hormone

The cycle of aminopeptidase activity demonstrated by histochemical methods in the activated excretory gland could not be detected in homogenates. In the electron microscope, the secretory granules in dormant glands were dense and irregular in shape and the mitochondria elongate, relatively dense, and with a crenellated outer membrane. The excretory gland was activated when the neuroendocrine system was stimulated by farnesyl methyl ether. In activated glands the secretory granules became larger, less dense and the membranes began to fuse with membranes of the ductules which ramify through the gland. The mitochondria became swollen. Aminopeptidase activity was displayed by a large uniformly less dense granules but not by the denser granules, and was seen in the endoplasmic reticulum, Golgi apparatus and in the lumen of the ducts. It is suggested that the ecdysial hormone from the neurosecretory cells sets in train a sequence of events which leads to entry of water into the gland and consequent activation of the enzyme in the granules, and to changes in the membranes of the granules which facilitate fusion with the membrane lining the ducts.     

The secretory nature of the excretory gland cells of Strephanurus dentatus. 3. Proteinase inhibitors

A proteinase inhibitor(s) was found in extracts of the excretory gland cells, intestines, esophagi, reproductive organs, and body walls from Stephanurus dentatus adults. The specific activity of the inhibitor(s) in the excretory gland cell extract was 45–175 times greater than in the other tissues. It is heat stable at pH 5.0 and inhibits the esterolytic activity of trypsin and chymotrypsin using p-toluenesulfonyl-l-arginine methyl ester hydrochloride (TAME) and benzoyl-l-tyrosine ethyl ester (BTEE) as the substrates, respectively, and also the proteolytic activity of both chymotrypsin and trypsin using casein as the substrate. S. dentatus adults maintained in NCTC 109 medium, secreted a trypsin inhibitor.     

The ultrastructure of the sinus gland of Carcinus maenas (Crustacea: Decapoda)

Summary The sinus gland of Carcinus maenas consists of the swollen axonal endings of the neurosecretory cells of the major ganglia and acts as a storage release centre for the membrane bound neurosecretory material. These neurosecretory granules fall into five different types based on size and electron density. Their contents are released by exocytosis of the primary granules or smaller units budded from the primary granules.I thank Professor E. Naylor for his constant advice and Professor E. W. Knight-Jones, Department of Zoology, University College, Swansea, for the provision of laboratory facilities. I am grateful to the Science Research Council for the financial support. Finally, I thank the Electron Microscope Unit, Southampton General Hospital, where the work was completed.     

An electron microscope autoradiographic study of DOC conversion to corticosterone in the rat adrenal cortex

Summary Seven thymuses from children between 1 and 12 years were examined by electron microscopy. Biopsies had been taken during surgical correction of congenital heart defects.In all cases we found interdigitating reticulum cells (IRC) in the medulla and inner cortex. These cells resembled the IRC which have been described previously in the thymus-dependent regions of the spleen and lymph node. They were characterized by an irregularly shaped nucleus, narrow cisterns of rough endoplasmic reticulum, and widespread interdigitation and invagination of the cell membrane. The surfaces of the IRC were in close contact with those of small lymphocytes, sometimes polysomal lymphatic cells, epithelial cells, and occasionally with those of lymphatic cells containing ergastoplasm.The IRC is apparently a specific cell of thymus-dependent regions. It may be that the IRC in the thymus, lymph node, and spleen contribute to the microenvironment needed for the differentiation of T-cells.Supported by the Deutsche Forschungsgemeinschaft, SFB 111/CII and III.—We wish to thank Miss M. Neubert and Mrs. R. Köpke for their technical assistance and Mrs. M. Soehring for her help with the translation.     

Sex differences in adrenocortical structure and function

Summary Adrenal glands of adult female rats are heavier than the glands of corresponding male rats. Postpubertal orchiectomy increases the adrenal weight, an effect restored by testosterone replacement. Under the same conditions ovariectomy of 8 weeks duration does not change the adrenal weight while estradiol replacement enhances the relative adrenal weight.Karyometric studies have shown that nuclei in the female zona fasciculata cells are larger (app. 18%) than those of the male. Similar but only slight differences (2%) were observed in the zona reticularis. Orchiectomy results in enlargement of cell nuclei within all zones of the adrenal cortex; testosterone replacement has the opposite effect. Ovariectomy of 8 weeks duration slightly enhances the volume of nuclei of the zona glomerulosa cells, has no effect on the nuclei of the zona fasciculata and reduces the volume of nuclei in the zona reticularis. Estradiol replacement reduces the volume of nuclei of the zona glomerulosa cells but increases nuclear volume in the zona fasciculata and in the zona reticularis.Thus testosterone has an inhibitory effect on the adrenal cortex of the rat while the physiologic effect of estradiol on the morphology of this gland, particularly on the zona fasciculata cells is rather dubious.The author wishes to thank Mrs. B. Westerska and Miss K. Siejak for excellent technical assistance.This research was supported in part by a grant from the Zoological Committee, 2nd Department, Polish Academy of Sciences.This paper is dedicated to the memory of late Kazimierz Mietkiewski, M.D., Ph.D. whose encouragements and suggestions were most stimulating for my work.     

Elektronenmikroskopische Zytomorphologie der männlichen Brustdrüse

Zusammenfassung Im Vergleich zu lichtmikroskopischen Untersuchungen an der Mamma virilis wird anhand von 2 operativ entfernten Brustdrüsen eines 57 und 63 Jahre alten Mannes die elektronenmikroskopisch erfaßbare Zytomorphologie beschrieben. Die Befunde werden den physiologischen Wachstumsimpulsen dieses Organs gegenübergestellt und Fragen der Zelldifferenzierung, der Desquamation und apokrinen Sekretion beantwortet. Elektronenmikroskopisch werden am Drüsenepithel Basalzellen, größere Zellen der oberflächlichen Zellreihen und Myoepithelzellen unterschieden. Diese Zellen entsprechen den Gangepithelien der weiblichen Brustdrüse und besitzen intracytoplasmatische Filamente. Diese stellen ein häufiges Differenzierungsprodukt des Zytoplasmas dar. Mechanismen einer Sekretion waren nicht nachweisbar. In die Drüsenlichtung werden pseudopodienartig vorgewölbte Zytoplasmateile abgeschnürt (Extrasionsvorgang). — Superfiziale Zellen werden desquamiert, wobei die Zytolyse in den marginalen Zytoplasmaschichten erfolgt. Kern und Teile des Zytoplasmas gelangen in die Drüsenlichtung. — Die Befunde zeigen die von Lebensalter und Proliferationsreiz abhängigen Vorgänge eines permanenten Zellersatzes in der männlichen Brustdrüse an.

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Ultrastructure of the mammary gland of the human male

Summary The ultrastructure of two mammary glands obtained operatively from a 57-year old and a 63-year old man was compared to the structure observed in the light microscope, and related to stimuli controlling growth of the gland, cellular differentiation and desquamation, and apocrine secretion. The glandular epithelium, which is analogous to that of the female mammary gland, is differentiated into basic cells, large superficial cells, and myoepithelial cells. The cells have intracytoplasmic filaments, that may be a sign of differentiation. Mechanisms for secretion were not observed, although pseudopodia-like parts of the cytoplasm are extruded into the glandular lumen. Superficial cells are desquamated, followed by cytolysis of their margins. These findings illustrate the replacement of cells due to age and altered stimuli.

Frl. St. Walter, lt. Assistentin des elektronenmikroskopischen Labors, danken wir für Präparationen und Photoarbeiten.     

Les tissus élaborateurs d'hormones stéroïdes chez les amphibiens urodèles

Résumé Les cellules du tissu glandulaire du testicule et de la glande interrénale de pleurodèle montrent les caractères généralement observés dans les cellules stéroïdogènes. Des différences existent entre les deux tissus. Le reticulum endoplasmique du tissu glandulaire est très développé et présent dans toutes les cellules qui sont d'aspect homogène. Au contraire, le tissu interrénal montre deux aspects cellulaires différents. Le premier se caractérise par un reticulum endoplasmique lisse relativement peu développé par rapport au tissu glandulaire, par des mitochondries petites et nombreuses, enfin par des liposomes denses et petits. Le deuxième aspect au contraire, se distingue par le petit nombre de mitochondries souvent géantes et à crêtes plus fréquemment organisées en faisceaux, par des liposomes nombreux de grandes dimensions et peu denses aux électrons.Le tissu glandulaire est très peu touché par l'hypophysectomie. Le reticulum persiste plusieurs mois comme d'ailleurs l'activité 5-3 -hydroxystéroïde deshydrogénase. Dans le tissu interrénal, la proportion des cellules d'aspects différents varie au profit des cellules à lipides abondants et à grandes mitochondries. L'activité 5-3 -hydroxystéroïde deshydrogénase est longtemps décelable.Le rôle du reticulum endoplasmique du tissu glandulaire est discuté en fonction des observations réalisées dans d'autres cellules stéroïdogènes à reticulum abondant. La signification des deux aspects cellulaires observés dans l'interrénale est discutée en relation avec les résultats expérimentaux obtenus en particulier chez le rat.Cette étude révèle que les critères d'activité d'une cellule stéroïdogène sont délicats à établir et doivent être différents d'un tissu à l'autre.

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Tissues secreting steroid hormones in urodele amphibians

Summary The fine structure of testis glandular tissue and interrenal gland cells of Pleurodeles shows the general features observed in other steroïdogenic cells. Certain differences exist between the two tissues. The agranular endoplasmic reticulum of the glandular tissue cells is well developed and present in all cells of similar appearance. On the contrary, the interrenal tissue cells show two different features. The first is characterised by a poorly developed smooth endoplasmic reticulum, compared with that of the glandular tissue, by small and numerous mitochondria, and finally by small electron dense lipid droplets. The second feature is the small number of mitochondria often giant and with fascicles of straight tubular cristae and numerous large lipid droplets of low electron density.The effect of hypophysectomy on the glandular tissue cells seem very slight. The endoplasmic reticulum and the 5-3 -hydroxysteroid dehydrogenase activity persists for several months. In the interrenal tissue, the proportions of the two different cellular features are modified. Cells rich in lipids and with large mitochondria are more abundant. It is possible to demonstrate a 5-3 -hydroxysteroid dehydrogenase activity for a long time after hypophysectomy. The functional significance of the agranular endoplasmic reticulum is discussed in relation to some other observations on different steroidogenic cells with a well developed agranular endoplasmic reticulum. The significance of the two cellular features observed in the interrenal gland is discussed in connection with experimental data obtained in the frog and the rat.This study shows that it is difficult to define criteria of cellular activity, which probably differ from one tissue to another.

Equipe de Recherche associée au C. N. R. S. Cytologie Ultrastructurale n 129.     

The fine structure of the newborn rat adrenal cortex

Summary The structural changes of the zona juxtamedullaris of the rat adrenal cortex at birth, have been examined by the light and the electron microscope. In this zone clusters of medullary cells lying among the strands of cortical tissue were observed. In the inner portion of the zona juxtamedullaris two types of adrenocortical cells were found: light and very-dark cells. The latter are smaller than the light cells and are always in close connection with the medullary tissue. The ultrastructural features of the very-dark cells suggest that these elements are in degeneration. This finding supports the hypothesis that at birth there is a partial degeneration of the rat zona juxtamedullaris, i.e. the zone corresponding to the fetal zone of some mammalian species.It is proposed that in all mammalian species at birth there is a partial regression of the zona juxtamedullaris and that the regression of the fetal zone is only the quantitative increase of this phenomenon. This hypothesis is discussed in relation to numerous data demonstrating that there are enzymatic conditions in the rat during fetal life, which permit a discrete hypertrophy of the adrenal cortex.The author wishes to express his appreciation to Dr. A. Gambino and to Mr. G. Gottardo for technical assistance.