An Unusual Sexually Dimorphic Mosaic Distribution of a Subset of Kallikreins in the Granular Convoluted Tubule of the Mouse Submandibular Gland Detected by an Antibody with Restricted Immunoreactivity

The granular convoluted tubule of the mouse submandibular gland contains a wide variety of biologically active proteins, including several kallikreins. The tubule is under multihormonal regulation, and is sexually dimorphic, being larger in males than in females. Correspondingly, levels of its various protein secretory products are more abundant in males than in females. However, isoelectric focussing studies show that the true tissue kallikrein, mK1, is more abundant in the female than in the male submandibular gland. In this study, an antiserum was prepared with restricted immunoreactivity for mouse mK1, and possibly other kallikrein family members of low abundance in the mouse submandibular gland, and used for the immunocytochemical staining of the granular convoluted tubule cells in the submandibular gland of adult male and female mice, by indirect enzyme-labeled and immunogold-labeled antibody methods for light and electron microscopy, respectively. The distribution of immunoreactive tubule cells showed an unusual sexual dimorphism. In males only a few scattered slender tubule cells were strongly stained, while the more typical large tubule cells were only occasionally weakly positive, and many of them were not stained. By contrast, in females slender tubule cells were not seen, and about two thirds of the more typical tubule cells showed moderate to strong immunostaining. Immunoelectron microscopy revealed that immunostaining was confined to the secretion granules in granular convoluted tubule cells in both sexes. The slender tubule cells of males had many strongly stained small apical secretion granules and occasional basal infoldings; in the weakly positive larger more typical tubule cells not all secretion granules were positive, and there was intergranular variation in the intensity of staining of positive granules. In females, although more tubule cells were stained, intergranular variations in staining intensity were also noted. In both sexes, many tubule cells did not contain any secretion granules that showed immunogold labeling for kallikreins. These findings establish that, in contrast to the situation for the majority of granular convoluted tubules proteins, mK1 and possibly other minor kallikrein family members are more abundant in the granular convoluted tubules of female mice, and that there is considerable variation in the content of these kallikreins not only between different tubule cells, but also in individual secretion granules in any given tubule cell in either sex.     

Immunocytochemical localization of renin in the submandibular gland of the mouse.

Renin was localized in the submandibular gland of the adult mouse at light and electron microscopic levels by the unlabeled antibody enzyme method of Sternberger. At the light microscopic level, renin was confined to the granular convoluted tubule (GCT) segment of the gland with considerable variation among GCT cells in intensity of staining. Some GCT cells failed to stain for renin. The pattern of staining was the same in the gland of male and female mice, but in the glands of females GCT segments were smaller and less numerous. At the electron microscopic level, staining for renin was also confined to the GCT cells, and was localized exclusively to the secretory granules. The intensity of staining of the secretory granules within a given GCT cell varied; some cells contained only minimally reactive or negative secretory granules. All other organelles within the GCT cell, except condensing vacuoles, failed to stain.     

Occurrence and Nuclear Localization of cAMP Response Element- Binding Protein in the Post-natal Development of the Rat Submandibular Gland

Cyclic AMP response element-binding protein (CREB) is a 43-kDa polypeptide that binds a cAMP response element located at the 5 promoter region of cAMP regulatory genes. The spatial and temporal distribution of CREB in the post-natal development of the rat submandibular gland was investigated using immunohistochemistry with a specific antibody. At birth, cells of the terminal tubules and ducts in the submandibular gland showed a nuclear CREB immunoreactivity of moderate intensity. At 1–2 weeks after birth, an intense CREB immunoreactivity was localized primarily to acinar cells. When the r352;-adrenergic agonist isoproterenol was administered to 2-week-old rats, a twofold transient increase in the number of immunoreactive acinar cells was induced. Beginning 3 weeks after birth, CREB immunoreactivity shifted from acini to the duct system and showed a clear localization in the cells of the intercalated ducts and distal portions of striated ducts, where the granular convoluted tubule develops after 4 weeks. Immunopositive materials were localized exclusively in the nuclei of both acinar and ductal immunoreactive cells. After the development of the granular convoluted tubules, CREB immunoreactivity was absent in the tubule cells and was gradually reduced in intensity over the entire gland. In order to examine a hypothesis that CREB is involved in the initial differentiation of the granular convoluted tubular cells, testosterone was administered to hypophysectomized adult rats. Whereas the tubular cells of hypophysectomized rats showed a complete regression, and no CREB immunoreactivity was found in any acinar or duct cells, administration of testosterone for a few days induced an intense CREB immunoreactivity in the nuclei of duct cells, followed by their differentiation into the granular convoluted tubular cells. These results suggested that CREB is involved not only in the growth and differentiation of acinar ce lls that are regulated by r352;-adrenergic nerves but also in those of the duct system, and especially in the androgen-regulated differentiation of the granular convoluted tubular cells, during the post-natal development of the rat submandibular gland.     

Histochemical evidence for lipoidal material in secretory granules of rat salivary glands

Synposis The granules of parotid acinar cells and submandibular granular tubule cells of rats contain one or more periodic acid-Schiff positive substances that are extracted during fixation with lipid solvents or acidic solutions or if frozen sections are stained in aqueous solutions. The granules in these cells can be stained by Schmorl's reaction, Luxol Fast Blue and a permanganate-Aldehyde Fuchsin sequence. The results obtained with these stains after a variety of fixation procedures strongly suggest that the secretory granules of these two cell types contain several components and that in parotid acinar and submandibular granular tubule cells, at least one of these components is a lipoidal substance.     

Prenatal development of the human submandibular gland

The prenatal development of the human submandibular gland has been investigated in 26 fetuses from the 10th week of gestation to full term. At 10-12 weeks, the glandular elements (primitive ducts and acini) were immature and surrounded by a loose mesenchyme. The acinar cell population increased gradually till the age of 32 weeks, and the rate of increase was diminished thereafter. At 16 weeks, intercalated and striated ducts were distinguished and their number increased till the age of 32 weeks when their number seemed to be stabilized. The development of the granular convoluted tubule cells from the proximal segments of striated ducts occupied the later stages of development. They appeared around the age of 20 weeks and proceeded till full term. At birth, the gland appeared devoid of mucous acini and fat cells and the secretory end-pieces were of the serous type. During the second trimester, periodic acid-Schiff- and alcian blue-positive secretory materials appeared in the epithelial cells of both ducts and acini, and in their lumina. This secretory activity was transitory and disappeared around the age of 28 weeks. The possible function of these secretory products is discussed.     

Immunohistochemical localization of S100A1 and S100A6 in postnatally developing salivary glands of rats

 S100 proteins are calcium-binding proteins of the EF-hand superfamily and are involved in the regulation of a number of cellular processes. The present study deals with the immunohistochemical expression of S100A1 and S100A6 in the rat submandibular and sublingual glands during postnatal development from day 0 to 12 weeks. Expression of S100A1 was particularly concentrated in pillar and transition cells in the granular convoluted tubule (GCT) and in striated duct cells of the submandibular gland age 4 weeks to maturity. None or only weak staining for S100A1 was observed in the duct segment at 0–5 days. On the contrary, immunostaining of S100A6 was present in proacinar cells in undifferentiated submandibular gland at age 3 days to 2 weeks. S100A6 immunoreactivity in rat submandibular gland coexisted with chromogranin reactivity. It is possible that S100A6 regulates secretion of chromogranin in proacinar cells. Secretion of growth factors and biologically active peptides in the GCT are regulated by calcium signals, and S100A1 may be involved in the secretory mechanism of granular cells. S100A1 and S100A6 are potentially of great importance in secretory functions of granular cells and proacinar cells, as well as in rat salivary glands. Accepted: 14 July 1998     

The postnatal development of the submandibular gland of the mouse

Summary The postnatal development of the submandibular gland was investigated in male mice of the Swiss-Webster strain, which were killed at 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 20 weeks of age, while the older mice had been weaned at 3 weeks of age. The mean weight of the submandibular gland increases from 9.5 mg at 1 week to 232.9 mg at 20 weeks of age, and the rate of increase is rapid between 3 and 10 weeks of age. The gland's contents of DNA, RNA and protein increase in a similar manner.The changes in the constituent cell types of the gland were studied in radioautographs prepared from Epon-embedded sections of mice given ³H-thymidine and stained with toluidine blue. At 1 week of age, the gland consists of acinar cells (36%), intercalated duct cells (26%), juxta-acinar cells (13%), striated duct cells (12%) and others. The cellular composition of the gland changes little before weaning, but the absolute number of all types of cells increases with age. Between 3 and 4 weeks, juxta-acinar cells disappear and granular convoluted tubule cells appear and increase rapidly in number with age. The rapid expansion of the population size of granular convoluted tubule cells after weaning coincides with the second peak of increased proliferative activity of intercalated duct cells, whereas all the other cell types show a progressive decrease in their proliferative activity with age. In spite of the burst in proliferative activity, there is no corresponding increase in the absolute number of intercalated duct cells. The number of striated duct cells peak at 5 weeks of age and then declines. These findings indicate that the mitoses of intercalated duct cells give rise to granular convoluted tubule cells through a stage of striated duct cells. At 20 weeks of age, the gland consists of granular convoluted tubule cells (47%), acinar cells (28%), intercalated duct cells (12%), striated duct cells (1%) and others.Supported by Public Health Service Research Grant AMDE 19753 from the National Institute of Health. The authors are indebted to Mr. I. Borcsanyi for technical assistance     

Kallikrein localization in rodent salivary glands and kidney with the immunoglobulin-enzyme bridge technique.

Kallikrein has been localized in rodent kidney and salivary glands by means of an immunoglobulin-enzyme bridge technique. In sections of kidney, anti-kallikrein antibodies bound to the apical region of certain distal tubule segments in the cortex, to reabsorption droplets of proximal convoluted tubules, and to certain duct segments in the papilla. In salivary glands of both male and female rats and mice, and apical rim of most striated duct cells of submandibular, parotid and sublingual glands and granular tubules of submandibular glands exhibited immunoreactivity. Granular intercalated duct cells in female submandibular glands also displayed immunostaining for kallikrein. Phenylephrine administration resulted in loss of immunoreactive granules from the granular convoluted tubule cells of male mouse submandibular gland. This response was paralleled by a biochemically demonstrable decrease in kallikrein-like tosylarginine methyl ester (TAME) esterase activity.     

Morphology and ultrastructure of a secretory region enclosed by the venom reservoir in social wasps (Insecta,Hymenoptera)

The morphology and ultrastructure of the convoluted gland inside the venom reservoir of four species of social Vespidae are described. The cells of the venom gland (including the convoluted gland) can be divided into six groups: (1) epithelial cells, (2) glandular cells with the end apparatus secreting into the tubule inside the convoluted gland (internal or embedded tubule), (3) a continuous arrangement of glandular cells with the end apparatus secreting directly into the venom reservoir, (4) glandular cells that are loosely dispersed along the tubule lumen between the free tubules and the embedded tubule of the convoluted gland, (5) secretory cells of the free tubules and (6) duct cells. One kind of secretory cell, hitherto unknown and described in this paper (group 3), is characterized by the presence of a well-developed end apparatus, usually with enlarged extracellular spaces, but lacking the normally associated duct cells. The secretory cells contain several stacks of granular endoplasmic reticulum, but these are mainly concentrated in the middle of the cell. The basal half of the cells contains many lipid droplets. Although the function of the convoluted gland is not yet understood, an hypothesis is related to what is known of the function of reservoir secretory cells in solitary wasps. All wasp species studied showed the same organization of the convoluted gland, which clearly distinguishes their venom gland from that of Sphecidae.     

Immunocytochemical localization of renin in the submandibular gland of the mouse during postnatal development.

The localization of renin in the developing mouse submandibular gland was studied immunocytochemically using the unlabelled antibody-enzyme method of Sternberger ('74). Bouin-fixed submandibular glands of mice of both sexes were examined at 5-day-intervals from birth (day 0) to 50 days of age. At all stages studied, only granular convoluted tubule (GCT) cells stained immunocytochemically for renin; such cells were first seen in glands of 30-day-old males and of 30-day-old females. The size and number of renin-containing GCT cells increased rapidly in males, attaining adult status by 50 days of age. In females, differentiation of GCT cells immunoreactive for renin was slower and less regular than in males, and at 50 days of age the GCT segment had not yet reached adult conditions with respect to the distribution of renin. Renin appears in GCT cells at later ages than other GCT cell products (e.g., EGF and amylase), suggesting the existence of independent developmental control for the expression of various biologically active substances in the GCTs.     

Developmental and androgenic regulation of the immunocytochemical distribution of mK1, a true tissue kallikrein, in the granular convoluted tubule of the mouse submandibular gland.

The action of androgens on the immunocytochemical distribution of mK1, a true tissue kallikrein, was examined in the submandibular gland (SMG) of developing and adult mice by indirect enzyme-labeled and immunogold-labeled antibody methods for light and electron microscopy, respectively. In both sexes at 3 weeks of age, essentially all of the immature granular convoluted tubule (GCT) cells were uniformly immunostained. At 4 weeks of age (the onset of puberty), morphological differences between the two sexes appeared in the GCTs, in which some cells became immunonegative. Thereafter, the immunonegative GCT cells became more abundant in the SMG of males than of females and considerable intercellular variation in staining intensity for mK1 was seen, especially in males. A few slender GCT cells with strong immunoreactivity appeared in GCT segments only in males. Castration of males resulted in an increase in the number of immunopositive GCT cells, whereas administration of dihydrotestosterone (DHT) decreased the number of immunopositive GCT cells in the SMGs of both sexes. Slender GCT cells immunoreactive for mK1 were seen in females treated with DHT for 6 days. However, there were no immunostained slender GCT cells in female SMGs after injection of DHT for 2 weeks. Immunoelectron microscopy disclosed this type of cell in male SMGs, which closely resembles immature GCT cells of prepubertal mice, with a few small secretory granules uniformly labeled with gold particles, a sparse Golgi apparatus and RER, and basal infoldings. In mature male SMGs and in SMGs of DHT-treated females and castrated males, typical GCT cells had a well-developed Golgi apparatus and a net-like RER but few to no basal infoldings, whereas in the female gland equivalent cells had moderately developed RER and some basal infoldings. These results suggest that mK1 is one of the enzymes characteristically present in immature GCT cells and that its synthesis is inhibited in part by androgens, resulting in decreased numbers of immunopositive cells.     

Immunocytochemical localization of epidermal growth factor in mouse submandibular gland.

The cellular and subcellular localization of epidermal growth factor in the submandibular glands of male and female adult mice was established by immunoperoxidase techniques. In light microscopic preparations epidermal growth factor was found exclusively in the granular convoluted tubules of the gland. The intensity of staining for epidermal growth factor varied from cell to cell, and some cells apparently were negative. The pattern of staining was similar in the glands of male and female mice; however, the granular convoluted tubules are androgen-responsive, and thus more extensive and composed of larger cells in males. In thin sections epidermal growth factor was most heavily concentrated in the secretion granules of the granular convoluted tubule cells. Within a given cell there was variation in intensity of staining of individual secretion granules, with some granules appearing minimally reactive or negative. The only other cell component with deposits of reaction product was the ribosomes.     

Thyroid medullary carcinoma of the Djungarian hamster Phodopus sungorus. Ultrastructural evidence for the production of normal and atypical intracellular granules

We have carried out an electron microscopic and immunocytochemical study of thyroid medullary carcinoma arising spontaneously in the Djungarian hamster, Phodopus sungorus. At the ultrastructural level the cytoplasm of tumor cells contained numerous round to slightly elongated, dense-cored secretory granules. The number of secretory granules differed from cell to cell in the tumor, being scanty in some cells but more or less abundant in most. Electron microscopic-immunocytochemistry demonstrated that all dense-cored secretory granules in all tumor cells exhibited calcitonin immunoreactivity. In approximately 10% of the tumor cells, unusual star-shaped secretory vesicles were also found in the cytoplasm. These vesicles contained a small, but well-defined, lucent core surrounded by a region of finely granular material of greater electron density. The outer contour of these unusual vesicles was stellate rather than smooth. They appeared to originate not from the Golgi complex, but from the rough endoplasmic reticulum. These atypical stellate vesicles did not show any calcitonin immunoreactivity. Furthermore, in a small number of tumor cells (approximately 1%) a third type of membrane enclosed structure was found. These were conspicuous rods 1-5 micron in length with tapering ends and a crystalline substructure. The presence of both normal and atypical secretory granules in some tumor cells suggests that carcinogenic transformation may interfere with the normal synthesis and assembly of secretory products by the cell.     

A comparative histochemical study of peroxidase activity in the submandibular glands of five mammalian species including man

Summary A light microscopic histochemical investigation of endogenous peroxidase activity in specimens of the submandibular salivary glands of man, hamster, rabbit, dog and guinea pig was carried out. A modification of the original Graham and Karnovsky diaminobenzidine (DAB)-hydrogen peroxide method was employed at different pH's.At all pH's (6.0, 7.6, and 9.0) a positive DAB reaction was found: in serous acinar cells in four of seven human submandibular glands, in convoluted tubule cells of the hamster, in acinar tissue, in secretory granular tubule cells and in the saliva of the guinea pig. This staining pattern was not markedly affected by KCN or 2,4-dichlorophenol (DCP). Furthermore, small cytoplasmic granules in collecting ducts of the dog displayed positive, KCN- and DCP-resistant DAB staining at all pH's tested. No reaction was observed in the acinar cells of the dog and rabbit glands.Mitochondrial oxidation of DAB in the striated duct cells occurred in all of the glands examined. Optimal staining of these cells was obtained at pH 6.0, but there was also strong positive staining at pH 7.6. At pH 9.0, however, the staining of the striated duct cells was very faint. The positive reaction in the striated duct cells was completely abolished by KCN.     

Immunohistochemistry of Grandry corpuscles in the oral mucosa of the duck bill: a light- and electron-microscopic study

Grandry corpuscles in the oral mucosa of the upper bill of the duck were immunohistochemically studied using antisera against calcitonin gene-related peptide (CGRP), galanin, methionine-enkephalin, neuropeptide Y (NPY), somatostatin, substance P (SP) and vasoactive intestinal peptide (VIP). Grandry corpuscles in the lamina propria selectively showed only SP-like immunoreactivity. Herbst corpuscles distributed near Grandry corpuscles were negative to all antisera applied. Although immunoreactive products in the Grandry corpuscles were found as granules in the peripheral cytoplasm of the Grandry cell, the axon terminals and satellite cells exhibited no reactivity. In pre-embedding electron-microscopic sections, SP-like immunoreactive products visualized with 3,3-diaminobezidine were localized in the granules of Grandry cells, but no labeling was observed in the cytoplasmic matrix or cell organelles. Electron-immunocytochemical labeling with colloidal gold by the post-embedding method clearly demonstrated that the SP antigen was localized only in the granules. It is presumed that Grandry cells have a secretory function. However, the function and the method of release of the SP contained in the observed granules remains obscure. Some CGRP-, NPY-, SP- and VIP-like-immunoreactive nerve fibers with varicosities associated with blood vessels and nerve fiber bundles of various sizes were observed in the lamina propria, but no such fibers penetrated into the intraepitherial layer. Nerve fibers positive for SP and VIP were also found in the interlobular connective tissue of the palatine glands. Some SP-positive neurons were detected in the vicinity of the palatine glands.     

Venom gland ontogeny in Formicinae, with special reference to the pulvinate convoluted gland (Hymenoptera, Formicidae)

 The primordia of the sclerites associated with the venom gland appear in third-stage larvae. The study aims to link the structure and function of this specialised venom structure in Formicinae, together with glandular ontogeny, and puts emphasis on the relevance of the distinguished glandular subunits contributing to the final secretion. The most conspicuous changes in glandular development occur in the pharate pupa. At this stage, all subunits of the venom gland (the tubule, the convoluted gland and reservoir) are visibly present. Formation of the glandular cuticle starts around day 4 of the pupal stage. Luminal cells in the convoluted gland are provided with abundant free ribosomes and apical microvilli that remain during adult life. Stacks of granular endoplasmic reticulum are also frequently found in these cells. The convoluted gland contains relatively few scattered secretory cells, belonging to type 3 according to Noirot and Quennedey (1974), which contain electron-dense material in their extracellular spaces during adult life. These cells strongly contrast with the apparently general non-glandular nature of the convoluted gland tubule. Histochemical investigation of the secretory cells in the pulvinate convoluted gland reveals that these cells contain lipoid material, most likely to correspond with lipoids demonstrated in earlier chemical analyses. This lipoidal material in minor quantities strongly contrasts with the bulk of acid constituting the secretion. The substances produced in the convoluted gland could act as insulators, thus protecting the insect against its corrosive venom. Accepted: 28 April 1998     

Cellular compartmentation of lysozyme and alpha-amylase in the mouse salivary glands. Immunogold approaches at light and electron microscopy level

The research was planned to study the subcellular distribution of enzymatic secretory products within the secretory structures of the mouse major salivary glands at light and electron microscopy level by immunogold silver stain (IGSS) technique and double-sided post-embedding immunogold binding and silver amplification in order to speculate about their compartmentation. In particular, we experimented the above immunogold labeling approaches to localize the lysozyme and to verify its distribution patterns in relation to another secretion enzyme, alpha-amylase. Co-presence of lysozyme and alpha-amylase was observed in the convoluted granular tubule cells of the submandibular gland and in the demilunar cells of the sublingual gland as well as in the electron-dense regions of the mottled secretory granules in the parotid gland. Exclusive binding patterns of lysozyme were observed in the acinar cells of the submandibular and sublingual glands where alpha-amylase did not occur.     

Androgen regulation of the cellular Distribution of the true tissue kallikrein mK1 in the submandibular gland of the mouse.

The kallikrein gene family encodes for at least four different proteases in the mouse submandibular gland (SMG): mK1 (true tissue kallikrein), mK9, mK13, and mK22. These enzymes and many other biologically active proteins are synthesized by the granular convoluted tubule (GCT), a specialized segment of the SMG duct system. The GCT is under multihormonal regulation by androgens, thyroid hormones, and adrenocortical hormones. Androgens suppress synthesis of mK1 in the SMG but enhance expression of the other three kallikreins. We prepared an antibody with limited immunoreactivity for mK1 and used it to examine the effects of androgen status on the distribution of this isozyme in the SMGs of developing and mature mice by immunoperoxidase staining for the light microscope and immunogold labeling for the electron microscope. In prepubertal mice, every immature GCT cell contains mK1, confined to an accumulation of small granules in the subluminal cytoplasm. In mature mice, not every GCT cell contains mK1, and in those cells that do there is considerable intergranular variation in the intensity of staining for mK1. GCT cells containing mK1 are much more abundant in the glands of females than of males, resulting in a peculiar sexually dimorphic mosaic distribution of this isozyme in the mature SMG. Castration of adult males increases the number of GCT cells expressing mK1. Administration of androgen to intact or castrated males or to intact females reduces the number of cells staining for mK1. In all cases, immunogold labeling for mK1 is confined to secretory granules. No fine structural differences were noted between cells that were positively or negatively stained for mK1. Therefore, although GCT cells appear to be composed of a uniform population of cells on the basis of morphology alone, they are not homogeneous in their content of secretory proteins. These results indicate that androgen regulation of GCT cells is more complex than has been appreciated to date.     

Fine structure of submandibular glands of mice with testicular feminization (Tfm/Y)

Summary The fine structure of the submandibular gland of the mouse with testicular feminization (Tfm/Y) was studied by light and electron microscopy. The architecture of the Tfm/Y gland proved to be rather similar to that of the normal female mouse in both tubular ratio and structure. Granular convoluted tubular cells in Tfm/Y mice characteristically had fewer secretory granules and increased cytoplasmic vacuoles than normal littermates, suggesting an altered synthesis of secretory granules in this cell type of the Tfm/Y mouse. Moreover, there were differences in the ultrastructure of submandibular glands between Tfm/Y and normal female mice. In the gland of the Tfm/Y mouse, basal striations of the striated secretory tubular cells were not so developed and granular intercalated duct cells were less than those of normal females. These findings support the evidence that the secretory tubule of the mouse submandibular gland responds to androgens, resulting in accentuated development in the male, while also suggesting the possibility that the mouse submandibular gland is regulated by other factors which lead to the prominent sexual dimorphism observed in this gland.     

Ultrastructural changes in the pars distalis of the maturing male rat

Anterior pituitary glands of male rats (2, 3, 5, 8, 12, 25, 36, 52, 56, and 62 days of age) were processed for electron microscopy. During early postnatal stages secretory cells are found in various stages of differentiation and comparatively few secretory granules are seen. Nuclei are mostly irregular, and the nucleo-cytoplasmic ratio is large. Many free ribosomes are present; the endoplasmic reticulum is generally sparse and the Golgi complex small or invisible. Cells are of variable shape, and numerous cytoplasmic processes project into large intercellular spaces. Many electron-dense cells which often contain myelinlike figures are seen. Lysosomes and lysosomal precursors are frequently found in secretory cells, predominantly in somatotrophs, of all immature glands. Mitotic figures are numerous in early stages after brith and decrease in number as the gland grows in size. A gradual increase in cytoplasmic volume with concomitant differentiation of cytoplasmic components as well as accumulation of secretory granules, accompanied by loss of myelin-like figures and decrease in the number of electron-dense cells, is observed as the animal reaches the prepuberal stage. Few lysosomes are seen in cells of mature glands. At 36 days of age all secretory cells seem to have differentiated, and morphological features as well as granule content show little change until puberty is reached. Gonadotrophs attain their characteristic morphology later than other cells. Cilia are observed in all developmental stages but are relatively infrequent in the mature gland. The described ultrastructural characteristics reflect the degree of maturation as well as the functional capacities of secretory cells at particular stages of development.