Gland Development Research Articles

Contemporary approaches to the study of salivary gland morphogenesis.

The submandibular gland of the mouse and rat serves as an important model to study epitheliomesenchymal interactions, since it can be studied both in vivo and in vitro. Previous work has established that the extracellular matrix, and especially the basal lamina, play vital roles in the development of this gland. More recent studies have indicated that integrins and several oncogene-related products, including components of the epidermal growth factor system, also play important roles in this gland's development.

Effects of green tea and tea catechins on the development of mammary gland.

To find whether green tea and tea catechins have effects on the development of mammary glands, virgin DDD mice were fed on diets containing green tea and tea catechins. The degree of mammary gland development was examined by duct-alveolar growth and DNA content. The results indicated that green tea, but not tea catechins, has a growth-promoting effect on mammary gland development.

Chemoprevention by dietary dehydroepiandrosterone against promotion/progression phase of radiation-induced mammary tumorigenesis in rats

When pregnant rats received whole body irradiations with 260 cGy gamma-ray at day 20 of pregnancy, and were then implanted with a diethylstilbestrol (DES) pellet for an experimental period of 1 year under feeding of a control diet, a high incidence (96.2%) of mammary tumors was observed. Administration of dietary 0.6% dehydroepiandrosterone (DHEA) together with DES implantation significantly decreased the incidence (35.0%) of mammary tumors. The first appearance of palpable tumors in the DHEA-fed group was 4.5 months later than that in the control group. For clarification of the mechanism of the chemopreventive action, we measured hormone levels in the serum of DHEA-fed rats. In the DHEA diet rats, the concentration of estradiol-17 beta exceeded, by approximately 6-fold, that in the control rats, while the levels of progesterone and prolactin were decreased by 30 and 45%, respectively. Interestingly, DHEA feeding prevented DES-induced hypertrophy of pituitary glands and DES-induced high level of prolactin in pituitary glands detected by immunohistochemical studies, but stimulated the development of mammary glands more than that in control rats treated with DES alone. These findings suggest that DHEA has a potent preventive activity against the promotion/progression phase of radiation-induced mammary tumorigenesis. The mechanism of chemoprevention by change of endocrinological environment is discussed.

Induction of Feline Acquired Immune Deficiency Syndrome by Feline Leukemia Virus: Alteration in Response to Hormones in the Hypothalamic-Pituitary-Gonadal System

Male kittens who were infected with the feline leukemia virus (FeLV) were found at various times after exposure to contain a sequence of dysfunction in their hypothalamic-pituitary-gonadal (HPG) system. To understand whether the involved endocrine glands in this system were damaged by FeLV, the hypothalamus, pituitary, and testes were tested for hormonal responsiveness in vivo and in vitro. The infected cats were administered with luteinizing hormone-releasing hormone (LHRH) and human chorionic gonadotropin (hCG). Their response to the treatment was studied, and they were then compared with untreated control cats. Normal response to LHRH for the synthesis of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were found in the infected cats prior to 10 weeks of infection. After 10 weeks, the response was reduced by 25%, 38%, and 42%, respectively. Twelve weeks after infection, the response to hCG for testosterone synthesis was drastically reduced. The control cats, however, demonstrated normal prolonged biphasic patterns of response to hCG. The in vivo administration of the tropic hormones had no effect on the titer of FeLV gs antigen in the blood of the infected cats. The medial basal hypothalamus (MBH) from the control cats and cats in their 13th week of infection were cultured in vitro, with the presence of high K+ ion (60 mM). The control MBH responded to K+ ion stimulation for LHRH release. The K(+)-stimulated release of LHRH in the control MBH was 99% higher than that of the infected MBH. In contrast, the amount of unreleased LHRH in the infected MBH was 74% higher than that of the control MBH. In in vitro culture, the control pituitary gland responded markedly higher to LHRH stimulation for the release of gonadotropins (FHS and LH) than that of the infected one (140% compared with 56% for FSH, and 70% compared with 28% for LH, respectively). Whereas, the amount of unreleased FSH and LH in the infected pituitary gland were 59% and 31%, higher than that of the control gland. These results suggest that (i) the progressive development of neuroendocrine glands' dysfunction is related to viral replication time; (ii) the in vivo and in vitro responses to tropic hormones in the infected endocrine glands are drastically reduced; and (iii) this reduction in hormonal response may be caused by defective regulation of peptide hormonal secretion.

Histochemical study of lectin binding in the human fetal minor salivary glands.

The emerging synthesis of glycoconjugates containing specific oligosaccharides in developing human fetal labial and lingual salivary glands has been investigated by lectin histochemistry. An avidin-biotin technique was used to study the binding of lectins from Ulex europeus I (UEA-I), Dolichos biflorus (DBA), Glycine maximus (SBA), Helix pomatia (HPA), Arachis hypogaea (PNA) and Triticum vulgare (WGA) to specific sugars on sections of tissue from labial glands, glands of Blandin and Nuhn, glands of von Ebner and the dorsoposterior lingual salivary glands. Incipient synthesis of glycoconjugates in early glands and their presence in the cells and ducts of the later glands was shown. The study also showed a time-related increase in both staining intensity and binding sites of serous acinar cells from all glands and for all lectins used. For mucous cells, peak intensity of staining was reached by the middle phase of development. During later gland development this intensity was maintained in dorsoposterior lingual glands but tended to decline in labial glands. The various lectins showed different degrees of binding but UEA-I lectin generally bound the L-fucose sugar group in all salivary glands at all gestational ages. The results showed that lectins appear to bind to the oligosaccharides on epithelial cell surfaces of fetal salivary glands at all stages of development. The degree of change depends upon the stage of differentiation and maturation of the glands.

Effects of Coumestrol and Equol on the Developing Reproductive Tract of the Rat

The phytoestrogens, coumestrol and equol, are weakly estrogenic. Here, we have examined their ability to induce responses in the neonatal rat uterus. Potent estrogens such as diethylstilbestrol (DES) and 17 beta-estradiol which initially double uterine weight on postnatal Day (PND) 5 when given on PND 1-5 subsequently reduce both uterine growth and gland development at later ages. In this study, Sprague-Dawley pups were treated neonatally (PND 1-5) with various doses of coumestrol and equol, and sacrificed at different ages to determine alterations in biochemical and morphological endpoints. Other rats were injected with the same compounds during the critical period of gland genesis (PND 10-14) to examine their effects on gland development. At the 100 micrograms coumestrol dose, on PND 1-5, premature gland development and increased uterine weight were observed. However, at later ages, uterine weight was significantly lowered and there was a severe suppression in the estrogen receptor (ER) levels. Equol lowered uterine weight at the later ages but did not affect ER levels. When given on PND 10-14, both coumestrol and equol caused a dose-dependent inhibition of gland genesis though not as severe as either DES or tamoxifen. Coumestrol was about 10(3) more potent than equol as an estrogen and behaved much like DES with respect to its effects on uterine weight, glands, and ER levels. At the doses used in this study, equol failed to demonstrate either estrogenic or antiestrogenic activity.

Gland Development on Leaf Surfaces of Nepeta racemosa

Trichomes present on the leaf surface of catmint (Nepeta racemosa L.) were examined using both scanning and transmission electron microscopy. Three types of trichomes were observed: (a) multicellular, uniseriate, nonglandular hairs, (b) small capitate glands with two cells in the head, and (c) large, peltate glands with four secretory/head cells. Secretory cells of capitate glands exhibited typical transfer cell morphology, with an abundance of RER and Golgi bodies, indicative of secretion of mainly hydrophilic substances. Mature peltate glands exhibited a distended cuticle and large subcuticular cavity, presumably containing the essential oils. Morphologically well-developed peltate glands were observed on young leaf primordia, with development occurring earlier at the leaf apex and along the midvein than at the leaf margins or base. Four major stages in the development of the peltate gland secretory cells were identified. The first stage was marked by highly vacuolated cytoplasm and normal distribution ...

5-Hydroxytryptaminergic control of testes development through the androgenic gland in the red swamp crayfish,Procambarus clarkii

Summary The possibility that 5-hydroxytryptamine (5-HT) stimulates testicular maturation in the red swamp crayfish, Procambarus clarkii, was investigated. A series of 5-HT agonists and antagonists was used in addition to 5-HT itself. 5-HT and its agonists not only induced testicular maturation but also development of the androgenic glands. In contrast, the 5-HT antagonists had no stimulatory effects on the testes or androgenic gland. This stimulatory action of 5-HT is hypothesized to be indirect, 5-HT stimulating release of the gonad-stimulating hormone, which in turn activates the androgenic gland to synthesize and release androgenic gland hormone, and the androgenic gland hormone then triggers testicular maturation.

Differentiation of the gonads and initiation of mammary gland and scrotum development in the brushtail possum Trichosurus vulpecula (Marsupialia)

The first appearance of the mammary and scrotal primordia and the sexual differentiation of the gonads of the brushtail possum, Trichosurus vulpecula, are described. Primordial germ cells were first observed, in fetuses of 7.5 mm crown-rump length, in the gonadal ridges and migrating up the dorsal mesentery. Mammary primordia were first observed in fetuses of 11 mm, and scrotal primordia in those of 12 mm crown-rump length. These structures were diagnostic of female and male brushtail possums respectively. Processus vaginales and gubernacula showed sexual dimorphism, being better developed and appearing earlier in males than in females. Sexual differentiation of the gonads occurred after the appearance of mammary and scrotal primordia, the testes being first recognisable in a 14.5-mm fetus and the ovaries postnatally. Birth occurred between the stages of 14 and 15 mm crown-rump length. These observations appear to indicate that the development of mammary and scrotal primordia are not under gonadal hormonal control, but under direct genetic control, as suggested for the tammar wallaby by previous authors.

The development and patterning of stomata and glands in the epidermis of Peperomia.

The leaf epidermis of Peperomia obtusifolia includes both stomata and glands, distributed in a joint spacing pattern. The questions asked concerned the relations between the development of glands and stomata and the determination of their distributions within the epidermis. For these purposes it was essential to follow development in vivo, by repeated replicas of the same epidermal surface. The development of both stomata and glands started by characteristic divisions. These were generally unequal and it was the smaller product that became the mother cell of the future specialized structure. The initial divisions differed, so that the nature of the mature structure, as a stoma or a gland, could normally be predicted at an early stage. But glands and stomata still shared developmental processes: their formation involved additional characteristic divisions in the mother cell and oriented divisions in neighbouring cells. Furthermore, some lineages started as glands and matured as stomata and vice versa. Statistical measurements showed that each individual structure was surrounded by a region that was free of both similar and other specialized structures. Where these regions involved stomata they could be accounted for by the cell lineages forming not only a stoma or a gland but also their surrounding cells. Yet the relations between neighbouring glands had an additional component, indicating a specific inhibition that declined gradually as the distance from the gland increased.

Female syrian hamster harderian gland: Development and effects of high environmental temperature and melatonin injections on histology and porphyrin deposits

We have investigated the development of the Harderian glands of female Syrian hamsters from birth to 8 months of age. The effects of melatonin injections on Harderian gland histology and porphyrin deposits of female hamsters exposed to two different temperatures were also studied. The morphology of the Harderian glands from 30-day-old female hamsters resembled those of sexually mature adult animals. The intraluminal area occupied by porphyrins increased significantly between 20 to 30 days of age. However, the relative number of mast cells per mm2 rose between 30 to 90 days. Both porphyrins and mast cell numbers appeared clearly reduced in the 8-month-old group. Secretory cells characterized by large lipid droplets (type II cells) were not observed. Daily afternoon injections of 25 micrograms of melatonin to female hamsters exposed to 22 degrees C for 14 weeks resulted in the discontinuity of estrous cyclicity, a marked decrease in the intraluminal area occupied by porphyrins, a reduction of the number of mast cells per mm2, and in a marked augmentation of the number of type II cells per mm2. Although the administration of similar dosages of melatonin to hamsters exposed to an environmental temperature of 32 degrees C did not interrupt estrous cycles, a clear reduction of the area occupied by porphyrins was observed. However, the number of mast cells and type II cells per mm2 was unaffected in these animals. Our results suggest that hormones other than ovarian steroids are involved in the regulation of the female hamster Harderian glands. The possible role of melatonin on Harderian gland metabolism is discussed.

Postnatal development of von Ebner's glands: accumulation of a protein of the lipocalin superfamily in taste papillae of rat tongue.

Antibodies produced against rat von Ebner's gland (VEG) protein, a recently characterized member of a lipophilic ligand carrier protein family, detect this protein immunocytochemically in von Ebner's gland acini and show that it is present at high concentrations in the clefts of circumvallate and foliate papillae. During embryonic development, von Ebner's gland anlagen are innervated (as shown immunocytochemically using neuronal specific antibodies) as early as embryonic day 20, before lateral glandular outgrowth and VEG protein can be observed. Expression of the VEG protein as determined by in situ hybridization and immunocytochemistry begins at postnatal day-2 cells in differentiating and branching off from von Ebner's gland ducts, and sharply increases with further enlargement and maturation of the gland. The close temporal correlation of von Ebner's gland innervation and VEG protein expression with papilla innervation and taste-bud development suggests a functional relationship of both structures. VEG protein might control access of lipophilic sapid molecules, such as bitter substances, to the gustatory receptors.

Cloacal anatomy of metamorphosed and neotenic salamanders

Ambystoma gracile is a polymorphic species, with some individuals attaining sexual maturity in the larval form. Such neotenic A. gracile retain larval characters in nonreproductive tissues. The cloacal anatomy of metamorphosed and neotenic individuals of both sexes was examined to determine the degree to which the larval state is reflected in reproductive structures. No difference in anatomy or onset of development of cloacal glands exists between metamorphosed and neotenic salamanders; thus, individuals should be capable of interbreeding. One autotriploid male showed few signs of cloacal gland development despite well-developed somatic growth, which supports the hypothesis of delayed maturity or sterility in male polyploid salamanders.

Tyrosine kinase receptor--nuclear protooncogene interactions in breast cancer.

In summary, evidence is beginning to accumulate in support of a major role for tyrosine kinase receptors (and their activating growth factors) and steroid hormones and their receptors in normal development and differentiation of the mammary gland. A point of intersection of their mechanisms of action in growth control appears to be the induction of nuclear protooncogenes such as c-myc. When c-myc is amplified, as it is in many breast cancers, EGF and FGF receptor tyrosine kinase action becomes transforming, not simply mitogenic. A source of the transforming factors could be either stromal or epithelial. This mechanism could function early in the progression of breast cancer. c-erbB-2 and EGF receptor overexpression and amplification, when they occur, appear to render tumors even more malignant and of especially poor prognosis. These mechanisms could function late in the progression of breast cancer. Transgenic mouse studies have begun to echo these themes. They have established that a growth factor (TGF-alpha) and its receptor (EGF receptor), which appear to be important in normal mouse and human proliferation and gland development, and a protooncogene (c-myc), commonly amplified and overexpressed in human and mouse breast cancer, can each contribute to mammary carcinogenesis. The mechanisms of the two are likely to be distinct. myc is likely to be acting as a tumor initiator in combination with normal proliferative factors, whereas TGF-alpha is likely to be acting as a hyperproliferative (promotional) factor in combination with a normal background of mutational events. The role of unmutated but amplified erbB-2 in the transgenic mouse is not yet known.

Prenatal development of human major salivary glands and immunohistochemical detection of keratins using monoclonal antibodies

The major salivary glands were examined from 69 human fetuses ranging from 10 to 40 weeks of gestation. Prenatal growth curves of developing salivary glands could be established by histological scoring, and development was divided into the early developmental stage (EDS) from 10 to 18 weeks, early intermediate developmental stage (EIDS) from 19 to 24 weeks, late intermediate developmental stage (LIDS) from 15 to 32 weeks, late developmental stage (LDS) from 33 to 40 weeks. Characteristic morphogenesis and cytodifferentiation occurred in glandular duct cells during the period of EIDS and LIDS. In the LDS, acini and ducts of the salivary glands histologically developed into a mature state similar to adult glands. Immunohistochemical staining with monoclonal antibodies (MoAbs) PKK1, KL1, K8.12, K8.13, K4.62, RPN 1160, 1162, 1163, 1164, and 1165 was performed. During the fetal period, keratin expression as revealed by MoAbs PKK1, KL1, K8.12 was well established, and the staining pattern for each of these antibodies was comparable. Other antibodies showed rare or negative staining except K8.13 which had a diffuse, non-specific staining pattern. Accordingly, the proliferation and cytodifferentiation of fetal stage keratin staining in ductal cells as revealed by MoAbs PKK1, KL1, and K8.12 showed a heterogenic distribution in both luminal and basal cells. It is a characteristic finding that the cytodifferentiation of ductal luminal cells precedes ductal basal cells. Ductal basal cells stained with MoAb K8.12 and show heterogeneity of keratin distribution continuously until the full term of gestation. The keratin staining of oral epithelium was also examined to compare with distribution of salivary gland ductal cells and oral epithelial cells. In the present study, the developmental sequence of salivary gland cells and the immunohistochemical properties of keratin proteins in these cells were described in relation to the histogenesis of salivary gland tumours.

Skin peptides in Xenopus laevis: morphological requirements for precursor processing in developing and regenerating granular skin glands.

The biosynthesis of the peptides caerulein and PGLa in granular skin glands of Xenopus laevis proceeds through a pathway that involves discrete morphological rearrangements of the entire secretory compartment. Immunocytochemical localization of these peptides during gland development indicates that biosynthetic precursors are synthesized in intact secretory cells, whereas posttranslational processing requires morphological reorganization to a vacuolated stage. The bulk of the processed secretory material is then stored in vacuolae-derived storage granules. In the mature gland, storage granules are still formed at a low level. However, in this case processing takes place in a distinct cytoplasmic structure, the multicored body, which we suggest to be functionally equivalent to vacuolae. When granular glands regenerate after having lost all their storage granules upon strong stimuli, another morphological pathway is used. 2 wk after gland depletion, secretory cells become arranged in a monolayer that covers the luminal surface of the gland. Storage granules are formed continuously within these intact secretory cells. Here, precursor processing does not require a vacuolated stage as in newly generated glands but occurs in multicored bodies. Most storage granules seem to be formed in the third week of regeneration. The high biosynthetic activity is also reflected by the high activity of the putative processing enzyme dipeptidyl aminopeptidase during this period of regeneration.

Light and electron microscopy changes in the endometrium caused by the administration of a norgestimate-containing oral contraceptive (Cilest)

Endometrium morphology has been analysed by means of light microscopy, scanning and transmission microscopy in patients before and during treatment with a norgestimate containing low dose combined pill (Cilest). Endometrium biopsies were taken after 1 (N = 3), 2 (N = 3), 3 (N = 7), 5 (N = 1) and 6 (N = 4) OC cycles. Light microscopy of the endometrium obtained during the OC-free pretreatment cycles shows a regular secretory transformed endometrium. During the first OC cycles of Cilest treatment slight growth retardation of endometrial glands was observed. Endometrium after 3 to 6 OC cycles showed an increasing delay of the growth of endometrial glands in terms of an abortive secretion. Morphometric studies revealed a retardation of the development of endometrial glands and an "arrest of secretion". The degree of proliferation varied slightly; a general delay between the date of the menstrual cycle and endometrial dating was evident. Using scanning electron microscopy the endometrium presented mostly a regular surface corresponding to the midcycle or a late proliferative phase up to the early secretory phase. Infiltrative dysplasia or inflammatory changes as well as local proliferations could not be detected. In transmission electron microscopy with semi-thin and ultrathin slices, stroma, structure of glands and surface appeared to be normal. Furthermore, no time delay between the endometrium and the day of menstrual cycle was observed. During treatment with a norgestimate containing low dose combined pill, only slight changes of the endometrium in terms of a growth retardation of endometrial glands were seen in the first 6 treatment cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Depressed Feeding by the Nematode Trichostrongylus colubriformis in Inoculated Goats

loc. cit.) that centrifugation alone may initiate migration of granules and surface lamination, but no further conversion to schistosomules occurs in water. It is possible that other kinds of agitation besides centrifugation may do the same thing. Cultivation in ELAC, saline and PBS at 37 C beyond 3 hr revealed that both saline and PBS organisms were slower than ELAC organisms in onset of esophageal gland granule migration (3 hr) and development of euchromatic nuclei (4872 hr). Even ELAC organisms lagged behind in in vivo schistosomules (Stirewalt et al., 1983, loc. cit.). Glycocalyx degradation, however, occurred at the same rate in all 3 types of incubation medium, but also was much slower than in vivo (Table II). These data demonstrate that conversion of cercariae to schistosomules can be brought about by the single simple procedure of cultivation of cercariae at 37 C in a medium such as ELAC, or even in saline or PBS. The changes occur more slowly in vitro than in vivo, and in saline and PBS than ELAC. Nevertheless, with this method of conversion, the large numbers of organisms required for preparation of a vaccine consisting of irradiated schistosomules, or for other immunological investigations, are easily obtainable. This study was supported by NIH Grant RR08005.

Pre-pubertal mammogenesis in the sheep 3. The effects of restricted feeding or daily administration of bovine growth hormone and bromocriptine on mammary growth and morphology

ABSTRACTIn crossbred female lambs reared on a concentrate diet between 8 and 20 weeks of age, a restriction in food intake to 40 g/kg body weight per day decreased live-weight gain (155 g/day) compared with that in control lambs fed ad libitum (284 g/day) and significantly reduced final live weight and the size of the mammary fat pad (P < 0·001). However, restricted lambs at 20 weeks had more total parenchymal deoxyribonucleic acid (DNA; 54·7 v. 47·5 mg) occupying a greater mass of mammary fat pad (17·0 v. 13·2 g) than control lambs (P > 0·10). Restricted feeding had little effect on mean plasma growth hormone (GH) concentrations at 12 and 18 weeks of age, but decreased plasma insulin and prolactin concentrations.In lambs fed ad libitum, daily subcutaneous (s.c.) injections of 0·1 mg bovine pituitary GH per kg live weight between 8 and 20 weeks of age significantly increased daily live-weight gain (347 g/day; P < 0·001) and also increased total mammary parenchymal DNA (71·2 mg; P < 0·10) and the mass of fat pad occupied by parenchymal tissue (20·6 g; P < 0·05), compared with the control treatment. Daily s.c. injection of bromocriptine (1 mg/day) had no effect on either body or mammary growth, but tended to reduce the effects of bovine GH when given in combination. Secretory activity was observed in the parenchymal tissue of the eight lambs receiving bovine GH alone, and also in five control lambs and three lambs receiving bromocriptine alone. Three lambs that had attained puberty by 20 weeks of age had the poorest mammary development of their respective treatment groups.Mammary gland development at 20 weeks of age was significantly correlated across treatment means with plasma GH concentrations estimated at 18 weeks of age (r = 0·95; P < 0·05), but no correlations of similar magnitude were found between individuals within treatments at 20 weeks. Strongest correlations were found among 8-week-old lambs, where mammary parenchymal DNA was positively correlated with mean plasma GH (r = 0·62) and the GH:insulin ratio (r = 0·79) and negatively correlated with the prolactin:GH ratio (r = -0·65).

Tracheal submucosal gland development in the rhesus monkey, Macaca mulatta: ultrastructure and histochemistry.

The submucosal glands are thought to be the primary source of the mucus overlying the primate trachea and conducting airways. This study characterizes the development of submucosal glands in the trachea of the rhesus monkey. Tracheas from 46 age-dated fetal, 8 postnatal and 3 adult rhesus were fixed in glutaraldehyde/paraformaldehyde and slices processed for electron microscopy. The earliest (70 days gestational age (DGA)) indication of gland development was the projection of a group of closely packed electron lucent cells with few organelles and small pockets of glycogen into the submucosa. This configuration was observed up to 110 DGA. In fetuses younger than 87 DGA it was present almost exclusively over cartilaginous areas. Between 80 and 140 DGA, a cylinder of electron lucent cells projected into the submucosal connective tissue perpendicular to the surface. In fetuses younger than 100 DGA, it was restricted to cartilaginous areas. By 90 DGA, some glycogen containing cells in proximal regions contained apical cored granules. By 106 DGA, cells in proximal areas contained apical electron lucent granules. More distal cells had abundant GER and electron dense granules. The most distal cells resembled the undifferentiated cells at younger ages. Ciliated cells were present in the most proximal portions of glands at 120 DGA. This glandular organization was found in older animals, including adults, with the following changes: abundance of proximal cells with electron lucent granules increased; abundance of distal cells with electron dense granules increased; and abundance of distal cells with abundant glycogen and few organelles decreased. We conclude that submucosal gland development in the rhesus monkey: is primarily a prenatal process; occurs first over cartilage; continues into the postnatal period; and involves secretory cell maturation in a proximal to distal sequence with mucous cells differentiating before serous cells.