The structure of Bowman's capsule as an index of age and sex variations in normal mice.код для вставкиСкачать
T H E STRUCTURE O F BOWMAN'S CAPSULE AS AN INDEX O F AGE AND S E X VARIATIONS I N NORXAL MICE CHARLOTTE CRABTREE Department of Zoology, Smith College, Northampton, Massachzi.setts SEVEN FIGURES I. INTRODUCTION Among mammals secondary sex characteristics include variations in a large number of unrelated structures. The size and shape of the masseter muscles, the character and distribution of hair, subcutaneous f a t distribution, the weights of various endocrine organs, and the shape of the glottis are a few of the many possible variations noted between males and females of the same species. A number of statements in recent articles have indicated the possibility of sexual variations in the normal kidney. I n 1927 MacKay and R'IacKay reported that the renal weights, in albino rats of all ages, bore a direct and constant relationship to body surface measurements. I n a second paper published the same year (MacKay and MacKay, '27 b) they modified this statement, indicating that sex was a factor influencing renal weights. I n the normal female albino rat the renal tissue per unit of body surface averages 27 mg. less than in the normal male. Hall and NcGregor ('3'7) found a sex difference in the renal weights of cats: females and young males maintain a constant kidney weight/ body weight ratio while in adult males the ratio is markedly increased owing to the deposition of fat in the tubular walls. Contributions from the Zoology Department, Smith College, No. 192. A thesis subinitted to the faculty of Smith College in partial fulfillinelit of t h e degree of Master of Arts. 395 396 CHARLOTTE CBABTREE An analagous condition has been demonstrated in the human kidney by Wald ( '37) who found the mean absolute weight of normal kidneys of the human female to be 40 to 75 gm. less than those of a similar representative group of males. There also exists a certain amount of evidence indicatiiig that renal weights a r e under hormonal influence and can be increased in both normal and gonadectomized animals by injections of sex hormones. Korenchevsky et al. found that young castrate rats treated with testosterone showed a definite and significant increase in renal weight (Korenchevsky, Dennison and Kohn-Speyer, ' 3 3 ) . I n the renal weights of castrated rats, the same workers found an increase of 6% to 24% when oestriii alone was injected, of 10% to 15% when male and female sex hormones were injected simultaneously (Koreiichevsky and Dennison, '34). Selye observed a comparable renal increase in normal female mice injected daily with small amounts of testosterone propionate. Histological study of these kidneys showed that the increase in weight was owing to hypertrophy of the secreting tubules and also to the preeence of numerous modified Bowman's capsules of the type to be described shortly (Selye, '39). These workers' results indicate that sex hormones have a stimulating effect on kidney weight. The vertebrate Bowman's capsule generally pictured in textbooks of normal histology is a goblet-shaped structure consisting of a double-walled sac of flattened cells. The inner, o r visceral layer of the capsule is continuous and non-syncytial in nature (Rensley and Beiisley, '30) and is closely applied to the capillary loops of the glomerular tuft. The outer, o r parietal layer is usually composed of a continuom, flat layer of epithelial cells which may or may not be separated from the visceral layer by the presence of filtrate in the lumen between the two layers. The entire capsule is surrounded by a structureless basement membrane which is deflected inward at the vascular pole and separates the cells of the glomerular endothelium from those of the visceral epithelium. The basement membrane is also continuous a t the urine pole with the STRUCTURE OF BOWMAN’S CAPSULE IN MICE 397 membrane surrounding the urinifcrous tubule. This area of juncture of the capsule arid the urinifcrous tubule is commonly designated as the neck. I n many cold-blooded animals a group of characteristically flattened ciliated cells make up a definite, fairly long, thin-walled neck seapent of the uriniferous tubule (von Rlollendorff, ’29). In reptiles, birds, and mammals, however, the neck is either much reduced or entirely absent, ‘’LOW“ CELL CAPSULE A ‘H\6YmCEU-CAPSULE a Fig. 1 A. Diagram of a ‘ L l o w ” cell capsule of the type usually described :IS characteristic of niamnialinii kidneys. B. Diagraui of a “high ” cell capsule with the squanious cells of tlie parietal layer replaced by cuboidal cells similar to those of tlie proxiirial convoluted tubule. and the transition from flat, squamous parietal cells of the capsule t o cuboidal cells of the tubule is usually very abrupt (see fig. 1 A ) . The development of the capsule in the human fetus and in iiifant,s in the first 2 years of postiiatal life has been worked out in detail (Risak, ’28; Gruenwald and Popper, ’40). The cells which develop into Bowman’s capsule are of mescnchpmal origin and appear first as a rounded sac of cuboidal and/or 398 CHARLOTTE CRABTREE columnar epithelium. As the adjaceiit glomerulus develops, it invaginates this sac to form a primitive capsule. The epithelium of the parietal layer is first to flatten. This process may occur even in the first half of embryonic life at which time the loops of‘ the glomerulus a r e closely adherent and the entire tuft is still covered with a layer of simple columnar epithelium cliaractcrized by large numbers of closely-grouped nuclei. a. d. b. e. C. f. CIS. DEVELOPMENT OF BOWMAN’S CAPSULE Fig. 2 Diagram showing the development of the human Bowman’s capsule. Based 011 the description of Gruenwald and Popper ( ’40). After birth the glomcrular loops fill with blood and expand, while the epithelial cell layer ruptures. Deep fissures are formed between the loops, thus exposing portions of naked endothelial malls which appear to be covered gradually by a thin layer of cells, the “glomerulothelium” of Randrath (’32) forming the visceral layer of the adult Bowman’s capsule (see fig. 2 ) . Whethei. the visceral layer of the capsule thus formed STRUCTURE OF BOWMAN'S CAPSULE IN MICE 399 is composed of cells modified from the primitive columnar epithelium originally present, as claimed by Zimmerman ('33) and others, or whether it is reticular in origin and develops from cells carried into the capsule via the vascular pole, a s suggested by von Mollendorff ( '27) and others, is a question beyond the scope of this paper. It is sufficient here to point out that, in the normal course of events, the parietal layer of Bowman's capsule in the human is invariably observed to be the first to flatten. These observations have been confirmed by the author in a series of kidney sections from premature infants from the Boston Lying I n Hospital. This description applies to the structure and development of the type of capsule most frequently observed and commonly described for mammals. As early a s 1887, however, Benda noted in mice kidneys a second type of capsule which differs from the description just given. The two types of capsules are essentially the same in structure save for the histological details of the neck and the parietal lamina of the capsule. I n the second type (in mice) the orifice from the capsule to the uriniferous tubule is wider than usual, and the neck is entirely absent. Instead of a n abrupt transition in this region from squamous to cuboidal epithelium, the cuboidal cells of the proximal convoluted tubule continue upwards into the capsule to varying extents, replacing the usual squamous cells of the parietal lamina. These cuboidal cells can frequently be found encroaching on the equator of the capsule, and occasionally extending as far a s the vascular pole. I n well-stained sections, brush borders are sometimes visible. At other times the cell outlines appear indistinct and irregular, with processes which protrude into the lumen (see fig. 1B). The observations of von Mollendorff ( '29), Rytand ( '38), and Carpenter ('39) confirm this finding. I n 1935 Bemliolz reported the existence of capsules of this type in a number of different species of mammals. I n the rabbit, pig, horse, guinea pig, fox and coon he observed no encroachment of cuboidal cells on the capsule. I n the mouse, dog, mink and woodchuck, however, he found large numbers of these modified 400 C H A R L O T T E CRABTREE capsules which were particularly numerous in the kidneys of four Pekinese dogs. He omitted mentioning tlie sex of the animals studied. Selye ('39), in the paper already cited, fouiid large numbers of this type of capsule in the hypertrophied kidneys of his testosterone-treated female mice. Helmholz ('35) noted in a human kidney from an infant with pyelonephyitis a similar continuation of cuboidal epithelium into the parietal layer of the capsule. I n a second case, that of a 9-year-old boy, he reported that some of the capsules showed development of cuboidal cells in the parietal lamina, while in others squamous cells similar to those of the typical human capsule made up the first part of the proximal convoluted tubule. Risak ('28) reported the presence of cuboidal cell capsules in an adult woman with chronic pyelonephritis, renal calculus, and hydroneplirosis. As an explanation of the occurrence of this type of mammalian capsule with high cuboidal cells in the parietal lamina, Risak ('28) suggested that they might be the result of arrested development, but was forced t o reject the hypothesis. Since the parietal layer is the first to flatten in the human (see fig. 2 D ) arrested development would be characterized by the presence of cuboidal cells in the visceral instead of the parietal lamina. Since one can also find in sections of young mouse kidney embryonic capsules with squamous cells composing the parietal lamina but columiiar cells still adhering to the glomernlar loops similar to those observed in the human, as well as cuboidal cell capsules such as those originally described by Henda (188?), it does not seem probable that these cuhoidal cell capsules represent arrested development in either the human or in the mouse. The findings of Bertelli ('30) are the converse of the results of the workers just cited: he claims to have observed in the normal frog, salamander, guinea pig, and cat, capsnles with the high columnar cells occurring more frequently in the visceral than in the parietal layer. I have been unable to confirm his observations in adult frogs or guinea pigs of either sex. STRUCTURE OF BOWMAN'S CAPSULE IN MICE 401 There is adequate evidence, a s indicated in this brief survey, that three facts have been established concerning variations in thc kidney in certain mammals: the kidneys of the two sexes vary in weight ; weight variations can be produced experimentally by castration or by injection of sex hormones; two types of Bowman's capsules occur normally. Indication that a correlation exists between the age and sex of the animal and the relative numbers of the two types of Bowman's capsules liere described has been reported in a preliminary publication (Crabtree, '40). Proof, based on diffcrciitial counts of the two types of capsules in a series of kidneys of mice of known age and sex, is here presented. 11. MATERIAL AND METHODS Twenty mice from five diffei*ent litters and two separate strains were used for this experiment : seven pairs were from the mixed stock of the Smith College animal colony, a hybrid stock exhibiting a large variety of external characteristics ; three pairs were pure albino from the Carworth F a r m stock. Males and females were placed in separate cages at the time of weaning and maintained on the regular stock diet. I n order to minimize the possibility of influencing genetic factors, litter mates were always used f o r comparisons between sexes of mice of any one age. The animals were killed by a blow on the head, and the kidneys removed immediately, washed in physiological salt solution, fixed for 6 hours in Susa, and dehydrated in Dioxan. Penetration of the fixative was insured by cutting the tissue into small pieces a t the end of the first hour of fixation. After fixation the tissues were transferred for 24 hours to Dioxan to which a little crystalized iodine had been added to remove the mercuric chloride of the fixative. Both kidneys of each animal were weighed together (correct to the nearest milligram) 24 hours after killing. Following dehydration for several days in Dioxan, the tissues were embedded in 56'48" paraffin and sectioned a t 6 u. One kidney of each animal was sectioned longitudinally and one transversely, and some sections of each kidney were stained with iron liaematoxylin and some with Mallory 's triple stain. One sec- 402 CHARLOTTE CRABTREE tioii of each stain from each kidney, making four slides in all, were selected for detailed study of each animal. Immediately following removal of the kidneys to fixative the remainder of the animal body was weighed directly, disregarding intestinal contents and blood loss. Thus the computed body weights and percentage weights are not accurate beyond a ienth of a gram, but are included in the report merely for comparison. All the Bowman’s capsules in four slides from each animal were counted and classified either as cuboidal o r “high” cell capsules or as syuamous or “low” cell capsules, as described above. Capsules were regarded as “high” if cuboidal cells of the parietal lamina extended around some part of the glomerulus o r if the cuboidal cells, in sections where the urine pole was visible, were definitely seen to encroach on the parietal lamina of the capsule. Capsules obviously embryonic, i.e., in which the two layers had not reached adult form, were disregarded. 111. RESULTS Tlie following table summarizes the actual numerical results obtained in counting and classifying the capsules in these mouse kidneys. The accuracy of this method is indicated by the uniform results obtained. I n only one slide of one animal (D7 0 ) was a percentage of low capsules found which varied more than 7% from the total average for that animal, o r which differed more than 10% from a corresponding average for any other single section from the same animal. As indicated in the above chart, a further increase in accuracy was sought in some animals of representative ages by counting a larger number of sections. Whenever serial sections were used, only every fourth or more section was studied so that the same capsule should not be counted twice. Since a capsule with cuboidal cells extending only partly around the parietal lamina can conceivably be cut in a number of planes which do not include the cuboidal cells, the figures quoted in the above table may be somewhat lower than the TABLE 1 Resilts of chsificatiow of capsules AGE I N mRIES NUMBER WEEKS D16 0 Birth D21 J Birth D15 0 2 D14 2 2 D24 0 D25 8 3 3 D13 0 4.5 D12 8 4.5 D28 9 7 D29 d 7 D60 9.5 s 9.5 D9 D26 0 D27 8 10.5 10.5 D70 11.5 D11 d 11.5 D8? 20 D10 8 20 s. Mal. No. low cap. Total no. cap. yolow cap. No. low cap. Total no. cap. yolow cap. No. low cap. Total no. cap. yolow cap. No. low cap. Total no. cap. yolow cap. No. low cap. Total no. cap. yolow cap. No. low cap. Total no. cap. yolow cap. No. low cap. Total no. cap. % low cap. No. low cap. Total no. cap. yolow cap. No. low cap. Total no. cap. % low cap. No. low cap. Total no. cap. % low cap. No. low cap. Total no. cap. % low cap. No. low cap. Total no. cap. Yo low cap. No. low cap. Total no. cap. yo low cap. No. low cap. Total no. cap. 70low cap. No. low cap. Total no. cap. % low cap. No. low cap. Total no. cap. yolow cap. No. low cap. Total no. cap. % low cap. No. low cap. Total no. cap. % low cap. xs. Mal. Is. FeH. xs. FeH. TOTALS 85% Figure based on a count of every 4th slide of a serial 91% 83% 83% 93% 99 82% 87% 59 90% 27 82% Figure based on a count of 30 sections from a serial Figure based on a count of 10 sections from a serial 56 59 38 55 82 54 79 79 70% 75% 68% 70% 37 53 31 50 53 88 78 49 64% 70% 60% 63% 56 76 103 65 73 137 91 106 77% 72 % 75% 71% 17 14 24 27 70 109 57 97 25% 24% 25% 25% 73 50 57 87 113 74 85 127 6996 6770 65% 68% 30 20 18 19 115 79 65 77 23% 26% 29% 25% Figure based on a count of 1 2 serial sections Figure based on a count of 12 serial section 40 31 85 107 37% 36% 29 13 84 196 15% 15% 42 36 94 88 45yo 41% 9 6 84 174 11% 3% 403 8770 114 131 87% 189 223 85% 1343 1603 84% 754 819 92 70 208 294 71% 171 270 63% 300 40 7 74yo 82 333 25% 267 399 67% 87 336 26% 967 1396 7070 216 1086 20% 124 385 32 % 80 513 16% 136 347 39% 31 503 6% 404 CHARLOTTE CRABTREE actual condition warrants. This possibility is equally present in all the sections examined, but for this reason the figures must be regarded not as absolute values, but as denoting a general trend toward a specific condition. There is little doubt that the capsules of both types are fairly equally distributed throughout the cortex ; since, in cross, longitudinal, and serial sections, uniform results were obtained. The following table correlates the numerical data from table 1with other data derived from the study of these animals. The weight ratios obtained in this study are in general agreement with results of other workers already cited. Although in prepnbertal groups the kidneys of the female mouse may be slightly larger than those of the male of correspondTABLE 2 Summary of rrsults of the study of normal kirln~ysin mice SERIES NUMBER SEX D16 0 D21dz D15 0 D14 d D24ly2 D25ldZ D13 ?! D12 6 D2S19 D29 * D60 D9 D26 D27 s 0 8 D7P nll d D80 n1o 6 'ER CENT WEIGHT AGE I N WEEKS KIDNCY \\EIGHT Birth Birth 1.1 3 0.0151 0.0149 0.0582 0.0929 0.1929 0.1773 4.5 4.5 0.0881 0.0828 1.6 7 7 9.5 9.5 10.5 10.5 11.5 11.5 20 30 0.3198 0.5130 ... 0.3049 0.3499 0.3628 0.3829 1.5 ...... ... 0.3276 0.4423 1.5 2 2 3 ...... PER CENT HIGH PER CENT L O W P 87 1.1 85 1.3 92 63 25 26 1.6 20 16 Carworth Farm stock. Figures based on counts of serial sections. 6 S T R U C T U R E O F BOWMAN’S CAPSULE I N MICE 405 ing age, in the older, mature animals the males’ kidney weight exceeds that of the females’. Except for the pairs killed at birth and at 10; weeks, the kidney in the male always constitutes a greater percentage of the total body weight than in the female. The relative numbers of the two types of capsules form a striking and significant unit of measurement f o r age and sex. I n young mice, 43 weeks or less in age, the percentage of cuboidal cell capsules is uniformly low in both sexes. With the onset of sexual maturity, which occurs somewhere between the fifth and sixth weeks in these strains of mice, a marked change is noted. I n the female the percentage of cuboidal cell capsules increases steadily but slowly until by 114 weeks more than half of the total number of capsules may be included in the high cell group. The greatest increase (50%) occurs between lo& and 11; weeks. I n the male, however, the increase is far more rapid and extensive. From 43 weeks through the twentieth week the male kidney always contains a higher percentage of cuboidal cell capsules than the kidney of a female litter mate. At the seventh week a large increase of high cell capsules suddenly occurs in the male; the kidney attains at this time a percentage of cuboidal cell capsules higher than is ever reached by the female. The relative numbers of cuboidal cell capsules continues to increase in the male until by the twentieth week 94% of all the capsules observed have some cuboidal cells in the parietal lamina. As already pointed out, the remaining 6% may have contained cuboidal cells, but were cut so that none of these cells were included in the section. Thus the presence of cuboidal cells in the parietal lamina is a normal occurrence in mice. The relative numbers of the two types of capsules is dependent on the age and sex of the animal. Renal sexual differentiation occurs earlier in the male than in the female, but in both sexes the percentage of cuboidal cells in the capsules tends to increase with age. The postpubertal male kidney, however, always has a higher per- 406 CHARLOTTE CRABTREE centage of cuboidal cell capsules than does the female of corresponding age. IV. DISCUSSION The exact nature of the cells which invade the parietal lamina is still not determined. Gorer (’40) listed these cells as characteristic of one of three types of renal lesions common to mice, but the above results indicate that, on the contrary, their occurrence is normal to the species. His statement: “None of the lesions appear to occur more frequently in either sex” is probably not based on statistical methods of examination. His observations of their frequent occurrence “in old members of the CBA strain” is in agreement with my findings. I n appearance the cuboidal cells of the capsules are continuous with and identical with the cells of the proximal convoluted tubule ; the cytoplasm is granular in appearance with brush borders usually demonstrable ; frequently basal granules can be seen. Pfeiffer, Emmel and Gardner (’40) state that mitochondria of the capsular cells are similar in structure and in intracellular location t o the mitochondria of the tubule cells. Still further evidence of the structural and physiological similarity of the cuboidal cells of the capsule and those making up the proximal convoluted tubule can be established by the use of vital staining. Trypan blue granules are characteristically collected and stored in the form of large crystals by the cuboidal cells of the proximal end of the proximal convoluted tubule. The kidney of a young mature male mouse (exact age unknown) treated with trypan blue was found t o exhibit characteristic storage of the large blue granules in the cells of the proximal convoluted tubule as expected, but also storage of stain in the cuboidal cells of the capsule whenever these cells were present (see fig. 3 ) . ‘ F o r 3 days the mnuse was given daily intraperitoneal injertions of about 1.5 cc. of a 1% trypan blue solution made up in 0.8% NaC1. A t the end of the third day the animal was killed, and the kidneys removed, preserved, and sectioned in the same manner as the others of this series. Mayer’s Paracarmine in 70% alcohol was used a8 a rounterstain, thus avoiding the use of water which tends to dissolve the trypan blue. STRUCTURE OF BOWMAN’S CAPSULE IN MICE 407 These granules were distributed in the cytoplasm around the nucleus in a n identical manner by both capsular and tubular cells. Save for an occasional granule in a macrophage either of the interstitial tissue of the medulla or in the connective tissue around a blood vessel, trypan blue crystals were found nowhere else in the kidney, indicating that this specific storage ability is characteristic only of this one type of renal epithelium. It would seem evident, therefore, that cuboidal cells of the capsule, if present, a r e identical with those of the .05rna Fig. 3 Camera lucida drawing showing the deposition of trypan blue granules in the cuboidal cells of the Bowman’s capsule and of the proximal cnd of the proximal convoluted tubule. proximal end of the proximal convoluted tubule. As the animal grows older the total number of capsules increases, but this increase is not in proportion to the rapid change in the percentage of high cell capsules. Thus in a single capsule a change from the squarvious to the cuboidal type is inferred, but there is no direct evidence t o prove whether the cuboidal cells arise from migration of tubular cells or metaplasia and differentiation of preexisting squanious epitlielium of the parietal lamina. 408 CHARLOTTE CRABTREE An interesting and probably significant correlation between the development of the mouse kidney and of the adjacent adrenal gland also exists. The origin, development, and subsequent degeneration of the androgenic or x-zone of the mouse adrenal has occupied the attention of a number of workers TABLE 3 Coniparison of the decelopment of the x-zone of the adrenal gland witA the number of cuboidal cell capsules in t h e kidney DIALE .4GE 1-3 weeks 4-5 weeks 7-8 weeks 10-12 weeks I FEMALE x-zone of tlie adrenal gland Early developmentSame as in f e of x-zone. Same male (8% t o as in fcmale 15%) X-zone begins t o Number begins t c atrophy increase (37%) X-zone entirely 75% high capsules gone .?yo to 10% in No change crease (80% tc 84%) No. of high re11 r a p - sules in the kidney Early develop- Same a s in male ment of x-zone. (13% t o 15%) Same as in malc X-zone continues Slight increase in to develop number (29%) No change No change X-zone degener- Peak number of ates female series (68%) reachcd for the last 10 years. Table 3 compares the times of appearance and disappearance of the x-zone a s noted by Dearisley (’28) with the times of sudden increase of cuboidal cell capsules of normal male and female kidneys. During the first 3 weeks of postnatal life both the kidneys and the adrenal glands of the two sexes a r e essentially alike. During the fifth week the x-zone of the male adrenal begins to Figures 4 t o 7 Photomicrographs of various capsules from mouse kidneys. Fig. 4 Capsule stained with Mallory’s triple stain t o show brush borders of the cuboidal cells of the capsule. Male mouse, 9.3 weeks old. X 350. Fig. 5 A “low” cell capsule with sqnamous cells making u p the entire parietal layer. Male mouse, 7 weeks. Fc. Haem. X 3.50. Fig. 6 A “high” cell capsules showing the continuity of the cuboidal cells with those of the adjoining proximal convoluted tubule. Adult male mouse. Fe. Haem. X 350. Fig. 7 A and B. Cuboidal cell capsules from a 7 weeks old male mouse. C. Similar capsule from the kidney of an adult male mouse. (a) Pen and ink schema of A. showing the extent of cytoplasm of the capsular ruhoidal cells. Fe. Haem. X 350. 410 CHARLOTTE CRABTREE degenerate, arid a t tlie same time the number of cuboidal cell capsules increases 29% as compared with a 13% increase of the female during the same pci*iod. By tlie end of the seveiith week, when degeneration of the male x-zone is nearing completion, the percentage of cuboidal cell capsules has made a n additional increase of 38% and is approaching the adult limit. I n the female the x-zone persists for 10 to 12 weeks, and concurrently the percentage of cuboidal cell capsules iaemains low until betweeii 10; and 11i weeks, when the relative numbers of this type of capsule jumps abruptly from 30% to 68%. I n both sexes, then, the number of cuboidal cell capsules of the noi*mal kidiiey remains low until the x-zone has disappeared, arid then rises abruptly to adult level. The above correlation in development is not surprising. Functional correlatioii between the adrenal and the gonads lias been established for some time, although the exact nature of the relationship is still f a r from being conipletely understood. I n view of this, and also in view of the embryological origin and anatomical relationships betweeii the adrenal, the genital, and tlie urinary systems, a direct correlatioii between tlie development of the adrerial tmcl the kidney would seem theoretically logical. I n the mouse kidney the relative number of capsules coiitaiiiiiig cuboidal cells in the parietal lamina varies with the age and sex of the animal, increases a t puberty, arid is at all times thereafter higher in the male than in the female of corresponding age. The rate of increase of the euboidal cell capsules is closely correlated with the development of the adrenal gland. These two facts point toward an endocrinological causative agent producing hypertrophy of the llarietal, but not the visceral lamina of Bowman’s capsule. Pfeiffer et 31. ( ’40) have injected estradiol benzoate, est~.ac’lioldipropioiiate, testosterone, and testosterone propionate into normal male mice, and Selye (’39) used testosterone propionate and cholesterol in normal females. Both obtained marked renal hypertrophy a i d noted particularly hypertrophp of the cells of the parietal lamina of Bowman’s capsule. A further study is STRUCTURE OF BOWMAN’S CAPSULE IN MICE 411 indicated to compare with the normals just established the effects on the kidney of castration and the injection of sex hormones. I have already collected data on this problem, and will publish it in a second communication. V. CONCLUSIONS 1. I n some species of mammals, including mice, the parietal layer of Bowman’s capsule normally may be partly o r completely composed of cuboidal cells instead of the more usual squamous epithelium. 2. Capsules of this type are not the product of arrested development. 3. Cuboidal cells in these capsules appear to be identical with those of the proximal convoluted tubule, and both exhibit the highly specialized ability to store granules of trypan blue vital stain, There is no direct evidence, however, to prove whether the cuboidal cells of the capsule arise as a result of migration of tubular cells or of metaplasia of preexisting squamous capsular cells. 4. Indirect evidence indicates that single capsules caii change from the low cell type to the high cell type. 5 . Cuboidal cell capsules are normally present in both sexes in mice of all ages studied. 6. After puberty the percentage of cuboidal cell capsules begins to increase. I n the male this occurs earlier than in the female, and the rate of increase is f a r greater-tending to approach 100% while that of the female of corresponding age always remains decidedly lower. 7. I n both sexes the relative numbers of cuboidal cell capsules remains low until degeneration of the x-zone of the adrenal gland has occurred, and then rises rapidly t o the adult level. This occurs at about 7 weeks of age in the male and about 11weeks in the female. 8. It is suggested that the increase of cuboidal cells in capsules is a specific response of the mouse kidney to an endocrine factor or factors. 412 CHARLOTTE CRABTREE 9. The numerical relationship between high cell and low cell capsules appears t o be a reliable index of age and sex changes in mice. The author wishes to take this opportunity to express her sincere appreciation to Dr. Myra M. Sampson f o r her helpful suggestions concerning the foregoing work. 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