摘要:

Summaryi. The head of the sea‐urchin spermatozoon is pear‐shaped and axially symmetrical. The sub‐microscopic morphology of the middle piece has not been investigated, but the tail, which terminates in an axial fibre, probably contains spiral or coiled structures, as in mammalian spermatozoa.2. Spermatozoa ofPsammechinus miliarisswim in spirals (frequency, 30–40 per sec), at an average translatory speed of 200/x/sec. at 18oC. This figure applies to very dilute suspensions. The spermatozoa ofEchinus esculentusdo not always swim in spirals.3. The evidence in favour of sea‐urchin spermatozoa being attracted by egg secretions is not conclusive. Experiments to settle this controversial question could be done without great difficulty.4. Little is known about the metabolism of sea‐urchin spermatozoa. The most important features are:(a)No movement in absence of oxygen.(b)Negligible acid production in presence or absence of oxygen.(c)Over certain limits, oxygen consumption per spermatozoon an inverse function of sperm concentration.(d)Cytochromesa, b, c, eanda3, succinic dehydrogenase, cocarboxylase, and catalase (in significant quantities) present.(e)Endogenous substrate unknown, though possibly carbohydrate.(f) Respiration inhibited by cyanide, and photo‐reversibly by carbon monoxide.A large number of substances, of widely different types, are said to stimulate or maintain the oxygen consumption of semen or spermatozoa. Among these are succinate, malonate, iodoacetate, copper, zinc, calcium, albumin and seminal plasma. The mode of action of these substances is in general obscure.5. Sea‐urchin spermatozoa contain a proteolytic enzyme which decreases the viscosity of gelatine, and desoxyribonuclease.6. Sea‐urchin spermatozoa contain or secrete three substances with characteristic chemical and biological properties. These substances and their principal characteristics are:(a)Androgamone I.Not a protein. Inhibits sperm movement in certain circumstances.(b)Androgamone II.Protein. Dissolves or precipitates egg jelly. Also called Antifertilizin.(c)Androgamone III.Not a protein. Liquefies egg cortex. Sometimes called Sperm Lysin.7. The spontaneously reversible agglutination of sea‐urchin spermatozoa in the presence of egg secretions, and in particular of Gynogamone II, has a number of characteristics in common with serological reactions. In recent years this subject has been extensively studied and reviewed by Tyler (1948). Some of the more important conclusions are:(a)Spermatozoa and G. II are multivalent with respect to their complementary combining groups, a condition which is responsible for the agglutination of spermatozoa in G. II.(b)Multivalent G. II can be converted into a univalent form in which it reacts with homologous spermatozoa, but without causing agglutination.(c)The sperm‐G. II reaction exhibits the zone phenomenon (maximum agglutination when the two reactants are present in particular proportions).(d)The sperm‐G. II reaction causes a reduction in the fertilizing capacity of a

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1951.tb00771.x

出版商:Blackwell Publishing Ltd    

年代:1951

数据来源: WILEY

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1951.tb00772.x

出版商:Blackwell Publishing Ltd    

年代:1951

数据来源: WILEY

摘要:

SummaryInvestigations made up to the present time on the action of male and female sex hormones on non‐sexual cells have been reviewed and the mode of action of these hormones discussed. The studies were made on rabbit fibrocytes and on amphibian eggs in various stages of development. The action of testosterone and of some of its derivatives was studied, together with that of oestradiol, and also of stilboestrol which is strongly oestrogenous although it does not occur in the animal body. The hormones were used in concentrations of i: 20,000 to 1: 1,000,000.1.Action of the male sex hormonesTestosterone and its derivatives scarcely slowed down growth in cultures of fibrocytes. Damage to cells showed itself by a characteristic change in the mechanism of mitosis, involving an increase in abnormal metaphases. According as the damage was weak or strong, fewer or more chromosomes failed to become attached to the spindle and lay outside the area of division.In experiments with Amphibia, the eggs ofTriton alpestriswere used in various stages of cleavage and at the beginning of gastrulation. The action of testosterone always began to show itself in the course of gastrulation and was most pronounced in the neurula stage. In 55% of cases neurulation was abnormal, in 19% of these embryos the medullary plate was defective on both sides and in 81% on one side only. In extreme cases half‐embryos arose, which appeared externally to be a mere pad of muscle. Sections showed that internally too they were only organized on one side, the mesoderm being undeveloped on the unorganized side while on the other side it was normally segmented.These disturbances of neurulation were correlated with an inhibition of growth. In the half‐embryos there were noticeably fewer mitoses on the undeveloped side, while with bilateral disturbances the number of mitoses was diminished on both sides. The abnormalities in mitosis were of the same nature as in the fibrocyte cultures.2.Action of the female sex hormonesOestrone and oestradiol were noticeably more effective than testosterone even at weaker concentrations. At higher concentrations (i: 10,000 to 1: 50,000) there was a complete standstill in 9 hours, while with weaker doses the metaphase was delayed and chromosome scattering became almost the rule, so that at the end of the period of observation up to 82 % of the equatorial plates were abnormal.Stilboestrol had a considerably stronger action than oestradiol and even in a concentration of 1: 200,000 led to a marked lengthening of the period of mitosis, owing to a blocking of early metaphase. The critical concentration was 1: 125,000; below this there was no effect.Female sex hormones acted much more strongly on amphibian eggs than on fibrocyte cultures. They already became effective in the course of cleavage, acting within a few hours from the beginning of an experiment. They upset the rhythm of cleavage in proportion to their concentration. Either the whole egg was affected or certain blastomeres were selected. Mitoses were always abnormal. The spindle was often loosened and the spindle fibres irregularly arranged. Among the pathological metaphases there occurred, together with equatorial plates with detached chromosomes, other types of injury such as an irregular arrangement of the chromosomes, incomplete dissolution of the resting nuclei, dwindled spindles and giant metaphases. Just as often the ana‐telophases were upset, in that delayed parting of the daughter chromosomes or incomplete dissolution of isolated sections of the nucleus were evident. The resting nuclei, too, were at times abnormal, but prophases were never affected.Besides the damage to nuclei, especially evident during mitosis, disturbances due to cytoplasmic damage were observed. These were evident above all in blastomeres of eggs which had been exposed to large doses of stilboestrol (1: 300,000 to 1: 500,000). They were apparent as early as 4 to 8 hours after the beginning of experiments and consisted in displacement of pigment, secondary dissolution of cell boundaries and the formation of cysts. In strongly damaged cells the spindle was absent, so that chromosomes lay in the middle of the yolk.Similar phenomena were observed in the egg ofTubifex.Here it was sufficient to place the eggs in the solution during metaphase for a breakdown of the whole nuclear apparatus to result.3.Influence of female sex hormones on the development of eggsOnly those eggs which had been exposed to strong doses of hormone showed abnormalities in morphogenesis. Gastrulation was often made impossible by an insufficiently developed or absent blastocoele. Only those embryos developed further which had completed an undisturbed gastrulation. But the medullary plates were mostly narrow and the medullary folds rudimentary. At best such embryos attained only the tail‐bud stage.To test the action of oestradiol and stilboestrol on growth and differentiation, newt embryos at Glasner's stage 29 were exposed to the hormone action. The disturbances occurred in all organs in which cell multiplication was active. Stil‐boestrol caused a stoppage of growth in the limb blastemas, while in the neural tube and in the retina the typical standstill occurred only in the matrix, with subsequent cell degeneration. In the central regions those cells which had already begun to differentiate proceeded no further.4.Action of the sex hormonesA possible connection between damage to mitosis and structural formulae was first investigated. For male hormones it was shown that unsaturated bonds always act by damaging mitoses, saturated bonds never. It was further shown that hormone specificity and damage to mitosis are wholly independent. Thus the damage caused by single male or female hormones is unaffected by the presence of a hormone of the opposite sex.In relation to the place of action of the harmful hormones, it was pointed out that carcinogenous hydrocarbons which cause the same damage to mitoses as sex hormones accumulate in certain lipophil cell structures, which may well be identical with mitochondria.The question of the relationship of the active steroids to nucleic acid metabolism was particularly studied. During gastrulation and neurulation there is a very intensive synthesis of nucleoproteids. Embryos treated with stilboestrol or oestradiol showed a disturbance in the distribution of nucleoproteids in single (? particular) cells and in the whole embryo. From this fact it was concluded that developmental processes and normal nucleoproteid metabolism are closely linked. In support of a direct connection there is the fact that an addition of nucleic acid to the harmful hormones is able completely or partially to neutralize their action. The observation that on the unorganized side of half‐neurulae produced by testosterone treatment there is a distinct decrease in the number of pyroninafnne granules lends support to the idea of a connection between nucleic acid metabolism and the mode of action of sex hormones.On a basis of the experimental results we arrive at the following scheme for the mode of action of sex hormones. The sex hormones accumulate inside cells at those places which are distinguished by their content of nucleoproteids, SH‐proteins and various enzyme systems, and which are important as metabolic centres in the life of the cell. The SH‐proteins which accompany nucleoproteids and play a decisive part in development are important in the detoxication of the harmful compounds but are not the primary point of attack of these hormones. The places at which sex hormones accumulate may be the mitochondria. Certain steroids are able to influence the synthesis and breakdown of nucleic acid through their structural peculiarities. The necessary preliminaries for the complete or partial synthesis of thymonucleic acid are thereby disturbed, just as by the use of the cytoplasmic nucleic acids. As a consequence abnormalities arise in the course of mitosis, with degeneration phenomena

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1951.tb00773.x

出版商:Blackwell Publishing Ltd    

年代:1951

数据来源: WILEY

摘要:

Summaryi. Degenerations of embryonic cells have either been reported as such or have been misinterpreted by various authors as ‘mitotic metabolites’ or blood cells.2. There is ample support for the morphological identification of dying cells from the following considerations: the degeneration ‘granules’ are initially Feulgen‐positive and have thus originated from nuclear constituents; the stages of cell deaths seen in normal embryos are identical with those produced experimentally and with those observed directly in tissue cultures; degenerating cells react in the same manner to supravital stainsin vivoandin vitro.3. The process of degeneration varies with the degree of specialization of the cell, with its functional state (e.g. mitosis), with the type of animal and under experimental conditions with the causative agents.4. Cell death may take from less than 1 hr. to about 7 hr. when only a small proportion of a living tissue dies, but may be prolonged to days when numerous cells die simultaneously and their resorption is delayed.5. Degenerations have been found during the normal development in embryos of all vertebrate animals examined. The occurrence of necrosis in embryos of pure genetical lines is excluded from this article.6. The incidence of embryonic cell deaths according to site, tissue, developmental stage or process and type of animal is summarized in Table 1.7. While some degenerations have no obvious function in embryonic development, others seem to play a significant role in embryonic processes, e.g. the morphogenesis and histogenesis of tissues and organs, and the representation and regression of phylogenetic steps (Table 2).8. Morphogenetic degenerations precede changes in the form of epithelial organs, e.g. during the invagination of the optic cup, the formation of the crystalline lens, the olfactory pit, the neural tube, etc. They bring about the separation of rudiments such as that of the neural tube and the lens from the ectoderm. They reduce the excessive thickening of uniting edges such as those of the body wall and of the mandibles. They are involved in the production of lumina in the solid rudiments of glands and the intestinal tract. In the mesenchyme they precede and make possible the influx of specialized tissue such as the sternal plates or the ingrowth of myogenic tissue in the mandible.9. Histiogenetic degenerations are related to the differentiation of tissues and organs. The differentiation of the three cell layers of the frog tadpole retina, for instance, is accompanied by three waves of degeneration. Similar cell deaths of early neuroblasts are found in the spinal ganglia outside the limb regions. In amphibia a partial sarcolysis during metamorphosis provides a blastema for the permanent musculature. Sex differentiation of the individual involves the partial degeneration of the Mullerian or Wolffian ducts. Cell deaths also occur in relation to fibre formation and to the appearance of bone and cartilage matrix. Their role in these and in evocatory processes needs further elucidation. Whether cell deaths in the central nervous system and the sense organs at the time of vascularization and neurotization are related to these phenomena remains to be further investigated.10. Phylogenetic cell deaths are of two types: those which represent a vestigial organ such as the paraphysis or the second muscle stage in higher vertebrates, and those concerned with the regression of larval structures such as the conjunctival papilla, parts of the ganglia of branchial nerves, of the pro‐ and mesonephros. Some of these larval organs have a function in embryonic development, viz. the apical ridge on the limb buds.11. The causation of the distinctly localized morphogenetic degenerations is obscure. Vascular or nutritional disturbances are unlikely to be responsible for these cell deaths which precede changes in form and appear in the same localizations and amounts in the vascularized tissue of the intact embryo and after explantation in tissue cultures.. Most of the histiogenetic and phylogenetic cell deaths, as well as some of the not strictly localized morphogenetic degenerations, may be due to the fading out of stimuli for their proliferation or for the completion of their differentiation. If such cells fail to divide, they age and die on reaching the end of their normal life span. This conception assumes that stimuli for the formation of embryonic tissues and organs act for limited periods only and extend over a field of cells. Some of these cells respond fully to stimulation, while others are late to react or do so only partially or receive only a fraction of the whole stimulus. The partial differentiation of cells unfits them for division, for dedifferentiation and redifferentiation in another direction.12. The localized morphogenetic degenerations are correlated with the incidence and orientation of mitosis and of cell movements, and changes in the form of embryonic organs are brought about by the integration of these three cellular activities. Cell deaths are abundant wherever the regular arrangement and close packing of cells prevent free cell movements; they are rare or absent when, as, for instance, in the tadpole eye, a loose arrangement of cells and a decrease in cell volume (by resorption of yolk) allow of free cell movements.14. Cell degeneration in vertebrate ontogeny is an important mechanism of integration of cells into tissues and organs by helping to shape the form of organs, by the removal of superfluous cells or by the preparation of a dedifferentiated blastema in histio‐ and

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1951.tb00774.x

出版商:Blackwell Publishing Ltd    

年代:1951

数据来源: WILEY

摘要:

SummaryThe many early hypotheses put forward to account for the production of hydrochloric acid by the stomach were based on electro‐, inorganic or organic chemistry. They are discussed and shown to be incorrect or incomplete. The site of hydrochloric production is the pericanalicular zone round the intracellular canaliculi of the oxyntic cells.Hydrochloric acid secretion in the intact animal and by isolated gastric mucosa can be stimulated by histamine; there is a concomitant rise in the rate of respiration. For every hydrogen ion secreted by the oxyntic cells there is an uptake of one molecule of carbon dioxide, and one bicarbonate ion is formed and exchanged for a chloride ion from the sodium chloride of the bloodin vivo, or of the saline solutionin vitro.The consequent increase in the sodium bicarbonate content of the blood leads to the ‘alkaline tide’ of the urine following acid secretion, and the hydration of carbon dioxide to form these bicarbonate ions is so rapid that carbonic anhydrase activity is required within oxyntic cells. The amount of this enzyme found in oxyntic cells is easily able to produce the required extra uptake of carbon dioxide. Virtually complete inhibition of carbonic anhydrase in isolated gastric mucosa leads to inhibition of acid secretion and damage to the cells indistinguishable from that occurring when acid secretion is stimulated by histamine in the absence of external supplies of carbon dioxide. A similar inhibition of carbonic anhydrase in the intact animal would lead to its speedy death by interference with carbon dioxide transport in the blood.The actively acid‐secreting stomach requires supplies of carbon dioxide from the arterial blood and has a negative respiratory quotient. There is an overall uptake of oxygen and carbon dioxide. The rate of acid secretion is so high relative to the oxygen uptake that the hydrogen ions cannot arise from, or be produced at the same rate as, acids such as pyruvic or carbonic formed during the normal course of oxidative metabolism with the oxyntic cells.The initial source of the hydrogen ions of the gastric juice must be largely or entirely the hydrogen atoms of water.There is a natural, maintained potential difference (p.d.) across gastric mucosa, the secretory surface being negative in an external circuit to the nutrient surface. When the two sides of the mucosa are connected electrically a continuous current can be maintained representing up to about 10% of the metabolic energy. The natural potential decreases with the onset of acid secretion. The rate of acid secretion can be increased or decreased by passing electric current from a battery through the mucosa so as to increase or decrease the p.d. across the tissue.Experiments with a variety of metabolic inhibitors show that the whole of the main pathways of aerobic respiration, fermentation and the related phosphorylations are apparently required to maintain the p.d. and acid secretion.The very high rates of acid secretion in mammalian oxyntic cells and the rates of secretion relative to the oxygen uptakes in amphibian oxyntic cells show that the thermodynamic efficiency of the process is remarkably high.The available evidence shows that two related mechanisms of acid secretion are possible. In mechanism i, the metabolic hydrogen atoms from glucose and water, which are transported by the dehydrogenases, become oxidized to hydrogen ions at the cytochrome level, and the electrons react with oxygen and water to form first hydroxyl ions, and then bicarbonate ions by further reactions with carbon dioxide. This process uses the redox energy from the level of atmospheric oxygen to that of the cytochromes.In mechanism 2, phosphate bond energy, generated by reactions at lower redox levels, is utilized to concentrate hydrogen ions, formed by ionization from water, in an electron‐cycle mechanism in which hydrogen ions are reduced to covalent hydrogen atoms, transported by a carrier system and oxidized to hydrogen ions at high concentration as a result of a coupled phosphorylation. Kinetic and thermodynamic considerations show that the hydrogen carrier and electron transport systems could be oxaloacetate‐malate and cytochromebor perhaps fumarate‐succinate and cytochromec.Both mechanisms require a spatial array of enzymes in the pericanalicular zone of the oxyntic cells, and in both cases chloride ions move in the opposite direction to, and as a result of, the movement of the electrons carried by the cytochromes.The rate of transport of water by the oxyntic cells is so enormous that it could not be handled molecule by molecule by any known enzyme systems. The water must be moved in bulk, and probably flows osmotically as a result of the secretion of the hydrogen and chloride ions by the

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1951.tb00775.x

出版商:Blackwell Publishing Ltd    

年代:1951

数据来源: WILEY