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Biomedical subjects

D C Herbert

Publications and source records attributed to D C Herbert.

At least 19 recordsLinked to original sources
PubMed1992

Expression of a human chimeric transferrin gene in senescent transgenic mice reflects the decrease of transferrin levels in aging humans.

Transgenic mice provide a means to study human gene expression in vivo throughout the aging process. A DNA sequence containing 668 bp of the 5' regulatory region of the human transferrin gene was fused to the bacterial reporter gene chloramphenicol acetyl transferase (TF-CAT) and introduced into the mouse genome. Expression of the human chimeric transferrin gene was similar to the tissue patterns of mouse and human transferrin. In aging transgenic mice, expression of the human chimeric transferrin gene was found to diminish 40% in livers between 18 and 26 months of age. Transferrin levels and serum iron levels in aging humans also diminish, as observed from measurements of total iron binding capacity and percent iron saturation in sera from 701 individuals ranging from 0 to 99 years of age. In contrast, in transgenic mice and nontransgenic mice, the mouse endogenous plasma transferrin and endogenous Tf mRNA increase significantly during aging. Neither the decrease of human TF-CAT nor the increase of mouse transferrin during aging appears to be part of a typical inflammatory reaction. Although the 5' regions of the human transferrin and mouse transferrin genes are homologous, sequence diversities exist which could account for the different responses to inflammation and aging observed.

Adolescent↗
PubMed1992

Intercellular communication within the rat anterior pituitary gland: IV. Changes in cell-to-cell communications during pregnancy.

Cell-to-cell communication by gap junctions was investigated in the female rat anterior pituitary gland from 9 through 21 days of pregnancy and subsequently on days 2 and 20 of the lactational period. Compared with intact estrus females, the major morphological characteristics of the pituitary gland during pregnancy were remarkably developed prolactin cells and gonadotrophs. A close relationship of both cell types was clearly evident. Gap junctions were present at each of the time intervals studied; however, they were noted only between adjacent folliculo-stellate cells. No remarkable changes were noted in the number of gap junctions during the middle stage of pregnancy (day 9 through day 15), with the relative number resembling that found in intact, 90-day-old controls during estrus (0.47 +/- .01 junctions/follicle-control vs. 0.50 +/- 0.08--day 15 of pregnancy). In the later stages of pregnancy (day 17 through day 21), a demonstrable increase was observed (0.64 +/- 0.10--day 17, 0.79 +/- 0.11--day 19 and 0.72 +/- 0.12--day 21), whereas during the lactation, this pattern returned to that seen at midpregnancy. Since both prolactin and the gonadal steroid hormones dramatically fluctuate during pregnancy and lactation, it is postulated that they may have an active role in gap junction formation during these two phases of reproductive life.

Animals↗
PubMed1992

Evidence that hepatocytes can phagocytize exogenous substances.

Although the phagocytic action of Kupffer cells is well known, such a phenomenon has not been well documented for hepatocytes. Following the injection of a suspension of egg lecithin-coated silicon particles (0.5-1.5 microns in diameter) into the portal vein of rats, Kupffer cells showed minimal phagocytotic action, which was in contrast to the hepatocytes which displayed numerous phagocytized silicon particles. By comparison, when noncoated silicon particles of the same diameter as those that were coated were injected into the portal vein, the opposite observation was made. There was no uniformity in the ability of the hepatocytes to phagocytize either coated or noncoated particles from one lobule to another. Some showed active phagocytosis, while in others no evidence of such a process was observed. These data provide strong evidence for the selective phagocytic action of liver hepatocytes.

Animals↗
PubMed1992

Effects of aging and food restriction on the trigeminal ganglion: a morphometric study.

A quantitative morphometric study of the rat trigeminal ganglion was conducted to determine the changes that occur with aging. All measurements were tracked from young to old age in two rat groups simultaneously. One group was fed ad libitum, the other was maintained on restricted food intake from 6 weeks on. Immunocytochemical and radioimmunoassay techniques were used to study the neuron group that produces the peptide, CGRP and to compare it with the CGRP-negative neuron group. We observed that in the trigeminal ganglion, soma diameters and nucleus diameters of all neurons, whether CGRP positive or negative, increased modestly with age; so did total ganglion weight. Food restriction delayed, but did not prevent the increases in neuron diameters. No significant changes occurred as a function of age in the total number of neurons per ganglion, the ratio of CGRP positive to CGRP negative neurons and ganglion content of CGRP. Food restriction did not affect the parameters that remained constant with age. These findings are in contrast to the marked inhibitory effect of food restriction on age-related increase in thyroid calcitonin, a hormone that is encoded by the same gene as CGRP.

Aging↗
PubMed1991

Intercellular communication within the rat anterior pituitary gland. III. Postnatal development and periodic changes of cell-to-cell communications in female rats.

Cell-to-cell communication by gap junctions was investigated in the female rat anterior pituitary gland from 10 through 45 days of postnatal development and in 60-day-old animals. Gap junctions initially appeared between adjacent folliculo-stellate cells on day 25. Their appearance in female rats was 5 days later than that observed in males (Soji et al., 1990). Gap junction number increased until the animals became 40 days of age, when they reached a level that resembled that found in adults. In addition, a correlation was evident between the frequency of gap junctions and stages of the estrous cycle, where they were most numerous during either proestrus or estrus. These results along with those previously published suggest that gap junction formation within the female rat hypophysis is in part modulated by both gonadal steroid hormones as well as prolactin.

Animals↗
PubMed1991

Cytochemistry of Ca(++)-dependent adenosine triphosphatase (Ca-ATPase) in rat anterior pituitary cells.

In the present study, we demonstrate the localization of Ca(++)-ATPase in the anterior pituitary of the male rat. Ca(++)-ATPase was mainly distributed on the membrane system of the granular cells, which included the plasma membrane, the outer mitochondrial membrane, the enveloping membrane of secretory granules, the smooth endoplasmic reticulum and some components of the Golgi complex. No reaction product was detected on the membrane of the rough endoplasmic reticulum or that surrounding the lysosomes. A positive reaction was clearly observed on the membranes surrounding 'large' secretory granules, while that present on the membranes of the 'small' granules was comparatively weak. The cells which contained the 'large' granules were interpreted as growth hormone-secreting cells and those in which the 'small' granules were located as gonadotrophs. There were either no reaction or one that was barely detectable on the plasma membrane of the folliculo-stellate cells. These data along with our previous findings (Soji, 1982, 1984) suggest that the membranous enzymes are not uniformly distributed over all pituitary cells but rather are specific for a given cell population(s).

Animals↗
PubMed1990

Human transferrin. Expression and iron modulation of chimeric genes in transgenic mice.

Transferrin (TF) is a plasma protein that transports and is regulated by iron. The aim of this study was to characterize human TF gene sequences that respond in vivo to cellular signals affecting expression in various tissues and to iron administration. Chimeric genes were constructed containing 152, 622, and 1152 base pairs (bp) of the human TF5'-flanking region with the coding region of a reporter gene, CAT (chloramphenicol acetyltransferase), and introduced into the germ line of mice. Transgenes containing TF 5'-flanking sequences to -152 bp were expressed poorly in all tissues examined. In contrast, transgenes containing TF sequences to -622 or -1152 bp were expressed at high levels in brain and liver, greater than or equal to 1000-fold higher than tissues such as heart and testes. Liver and brain are major sites of endogenous TF mRNA synthesis, but liver mRNA levels are 10-fold higher than brain. A significant diminution of CAT enzymatic activity in liver accompanied iron administration in both TF(0.67) and TF(1.2)CAT transgenic mice, mimicking the decrease of transferrin in humans following iron overload. Levels of endogenous plasma transferrin also decreased in iron-treated transgenic mice. Transgenic mouse lines carrying human TF chimeric genes will be useful models for analyzing the regulation of human transferrin by iron and for determining the molecular basis of transferrin regulation throughout mammalian development into the aging process.

Animals↗
PubMed1990

Intercellular communication within the rat anterior pituitary gland. I. Postnatal development and changes after injection of luteinizing hormone-releasing hormone (LH-RH) or testosterone.

The postnatal development of gap junction formation and cell-to-cell communication were investigated in male rats from 10 through 40 days of age. These junctions initially appeared between adjacent folliculo-stellate cells on day 20. Their numbers increased until the animals reached the age of 40 days, when their frequency reached a level that resembled that found in adults. The ontogeny of these junctions was examined in rats treated with luteinizing hormone releasing hormone (LH-RH) or testosterone. The two hormones were injected for 1 week into rats aged 3, 13, 23, or 33 days. The appearance of gap junctions was accelerated in a similar fashion by LH-RH and testosterone, with their formation and numbers being advanced by 10 days over that observed in the untreated controls. The results suggest a role for the gonadal steroid hormones in the formation of gap junctions in the rat hypophysis.

Animals↗
PubMed1990

Intercellular communication within the rat anterior pituitary gland. II. Castration effects and changes after injection of luteinizing hormone-releasing hormone (LH-RH) or testosterone.

This study investigated the relationship between gap junction formation and sex steroids in the male rat anterior pituitary gland. Animals were castrated at 5 days of age and separated into the following three groups: 1) oil-treated controls, 2) those injected with LH-RH, and 3) those given testosterone. On days 10, 20, 30, and 40, five rats in each group were sacrificed and their hypophyses removed for ultrastructural examination. When compared with age-matched, intact animals, there was a marked suppression in follicular development and in the number of gap junctions present in the pituitary glands of both the castrated controls as well as the castrates given luteinizing hormone releasing hormone (LH-RH). In contrast, the morphology of these structures in the animals given testosterone was indistinguishable from that observed in the intact controls. These observations provide more definitive evidence that in the male rat pituitary gland maturation of the structural organization of the follicles, including gap junction formation, requires an intact hypophyseal-gonadal axis and is highly dependent on the hormone testosterone.

Animals↗
PubMed1990

Tissue specific expression of mouse transferrin during development and aging.

Transferrin (TF) is a major plasma protein that binds ferric iron and transports it to all target tissues of the body. This study is the first step to identify the tissue specific expression of the transferrin gene in mice during development, into maturity and throughout the aging process. The transferrin gene expresses mainly in mouse liver, the cerebral hemispheres and cerebellum. In mouse, transferrin is expressed in peritoneal macrophages and in mouse macrophage cell line MO59. At 19 days of gestation, transferrin mRNA is detected in the fetal lung, heart, stomach and kidney. TF mRNA levels increase in liver throughout gestation with maximum expression occurring at 19 days. Transferrin mRNA was detected in placentas of pregnant mice, with levels progressively increasing throughout the term of pregnancy. The levels of liver TF mRNA in mouse vary in a cyclic manner during the development increasing with the aging processes. Because of the dynamic nature of tissue requirements for transferrin during homeostasis the TF gene serves as a promising system for analyzing tissue-specific regulation in vivo during development and aging. Results from this study designate periods in the life-span of the mouse where regulatory mechanisms interacting with the TF gene appear to dynamically alter its expression.

Aging↗
PubMed1989

Intercellular communication between rat anterior pituitary cells.

Cell-to-cell communication within the rat anterior pituitary was investigated in 60-day-old male rats with immunohistochemistry, scanning electron microscopy, freeze-fracture electron microscopy, and conventional transmission electron microscopy. A dense cytoreticular network of cytoplasmic processes from the folliculostellate cells was found to contain immunoreactive S-100 protein and was observed throughout the anterior pituitary. Nonimmunoreactive cells, which were granular, were situated in the center of each network. Almost all of the granulated cells were situated in close proximity to the folliculostellate cells. Scanning electron microscopy revealed that the gland consisted of microlobules enclosed by a basal lamina. On the surface of the microlobules were blood vessels whose branches invaded its internal structures. Cytoplasmic processes from folliculostellate cells projected outside the microlobule. Freeze-fracture electron microscopy demonstrated the presence of numerous intramembranous particles on the P-face of the plasma membrane. Scattered on the cell surface were groups of particles forming gap junctions. Meshworks of ridges which were representations of tight junctions were also observed near clusters of microvillous fragments. Clusters of particles forming small gap junctions were located between the meshworks of tight junctions. Small gap junctions were clearly observed by conventional electron microscopy between junctional complexes in a manner similar to that seen by freeze-fracture electron microscopy. Slender cytoplasmic processes of folliculostellate cells came in contact near the basal lamina and were adjoined by small gap junctions. The ratio of nongranular cells which contained gap junctions to those in which the junctions were absent was about 1:1. The size of the gap junctions ranged from 50 nm to 3 microns. No gap junctions were observed along the plasma membranes of the granular cells. The significance of an intercellular communication system within the anterior pituitary gland of the rat is to establish a mechanism for rapid transmission of information in an organ which lacks direct innervation.

Animals↗
PubMed1989

Granulated 'marginal cell layer' in the rat anterior pituitary gland.

A granulated 'marginal layer cell' was observed in the lining of Rathke's residual pouch of 5 and 10 day-old rat anterior pituitary glands. Immunohistochemistry was not employed to identify the precise function of these cells. However, the cytological characteristics of nearly all of the cells indicated that they resembled GH-secreting cells, with a few displaying morphological features of corticotrophs. In pituitary glands of 5-20 day-old rats, both ends of Rathke's residual pouch extended into the pars distalis at the site of transitional zone of this lobe and of the pars intermedia. The cells within the 'invading' residual pouch contained numerous microvilli. In the middle portion of the residual pouch, cavities lined by 'marginal layer cells' had numerous microvilli and were adjoined by junctional complexes. In the adult rat pituitary gland, there were no granulated cells in the 'marginal cell layer' and no invasion of the residual pouch into the anterior lobe. From these data the possible source of the follicle and of the folliculo-stellate cells in the anterior pituitary of the rat is proposed.

Animals↗
PubMed1988

Pituitary and testicular function in the restricted (Hre) rat.

A systematic morphological and biochemical examination of the pituitary-testicular axis in the male restricted (Hre) rat was undertaken in order to understand the possible site(s) and mechanism(s) responsible for their infertility. The adult Hre rat had increased plasma levels of LH and FSH but normal levels of prolactin and testosterone, and normal weights of the sex accessory glands. The increased plasma levels of LH and FSH correlated with hypertrophy and vacuolation of the gonadotrophs in Hre rats. Leydig cells from adult Hre rats exhibited an enhanced testosterone response to LH and hCG in vitro but not in vivo. There was a shift in the normal age-related decline in the response of cultured Sertoli cells to FSH in Hre rats, which was evident as early as 25 days of age, and which corresponded to a delay of 10-14 days in the pubertal increase in testicular weight. The search for the mechanism of the suppression of spermatogenesis in the Hre rat should take into account two events, which may or may not be related: (i) the delay in the onset of spermatogenesis during puberty and (ii) inhibition of spermatogenesis in the adult, which may result from abnormal function of both the Sertoli and Leydig cells.

Animals↗
PubMed1979

An autoradiographic and immunocytochemical study of the neonatal rat pituitary gland.

Two-day-old female rats were injected with 5 nmole/kg of 6,7-3H-11 beta-methoxy-17-ethylestradiol (R 2858 = moxestrol) and killed one hour later. The animals were decapitated and, the pituitary glands were removed, mounted on tissue holders and frozen in liquified propane. The tissue was then processed for autoradiography according to the thaw-mount technique. At the end of the exposure time, prior to photographic development, some of the tissue was fixed in 10% formalin and then photographically developed for autoradiography. The fixed tissue was subsequently stained immunocytochemically using antibodies to luteinizing hormone or prolactin. Between 10 and 15% of the cells of the pars distalis concentrated the synthetic estrogen or its metabolite. The immunocytochemical procedure revealed that both LH-gonadotrophs and lactotrophs concentrated the steroid. These studies along with earlier studies suggest that the neonatal rat pituitary contains only a small portion of the adult complement of estrogen receptors and that these receptors are dispersed across a number of cell types.

Animals↗
PubMed1979

Intercellular junctions in the rhesus monkey pars distalis.

Four rhesus monkey pituitary glands were examined by transmission electron microscopy. Three types of intercellular junctions, desmosomes, hemidesmosomes and zonula adherens-type junctions, were observed between adjacent granular cells, folliculo-stellate cells, and joining a folliculo-stellate cell with a granular cell. Demosomes were most commonly observed between granular cells while the zonula adherens-type junctions were generally found between the folliculo-stellate cells.

Animals↗
PubMed1979

Evidence for the autoregulation of hormone secretion by prolactin.

The cells from the 2B8 clonal strain of pituitary cells which previously have been reported to produce only PRL were incubated with varying amounts of ovine PRL (oPRL) ranging from 0.01--1000 ng/ml. After 1 h, significantly less PRL was measured in culture media from cells incubated with all doses of oPRL employed. This inhibition was dose related. The cells were rinsed five times with Hank's balanced salt solution and subsequently placed into PRL-free media for an additional hour. Hypersecretion of hormone occurred from those cells previously exposed to 1--1000 ng/ml oPRL. The PRL in the media from cells previously exposed to 0.01--0.1 ng/ml was similar to that in the control culture. In some experiments, the cellular concentration of PRL was determined at the end of each of the two 1-h incubation periods. After the initial exposure to oPRL, an increase in intracellular hormone was observed only in those groups incubated with 1--1000 ng/ml oPRL. In contrast, after the cells were rinsed and placed into PRL-free medium, the cellular concentration of PRL was unchanged in all groups except the group previously exposed to 100 ng/ml oPRL. These data indicate that PRL can inhibit its own secretion through direct action on the lactotrophs of the anterior pituitary gland.

Animals↗
PubMed1978

Immunocytological localization of LH, FSH, TSH and their subunits in the pituitary of normal and anencephalic human fetuses.

Immunostaining with antisera to oLH, hCG, hLH, pLHbeta, hFSH, hFSHbeta, hTSHalpha and bTSH was used to delineate the gonadotropic and thyrotropic cells of the human fetal anterior pituitary. Hypophyses from 29 normal fetuses, 3 newborn infants, and 5 totally ancencephalic fetuses were used. Several controls to check for the specificty of the immunocytological reaction were made. In normal fetuses, observations showed that: 1) the alpha subunit was detected from the eighth week and throughout gestation without sex differences; 2) intact LH was detected during the third month, however, age and sex differences were observed during the fourth and fifth months; 3) intact FSH was detected in female fetuses from the beginning of the fourth month, a sex difference was observed; 4) LH and FSH were detected in the same cells; 5) the thyrotropic cells were detectable from 15 weeks of gestation and their number increased during gestation without sex difference; 6) at birth the gonadotropic cells were scarce and were located in the ventromedian zone of the anterior pituitary, while the thyrotopic cells remained numerous and were located in the dorsomedian zone. In amencephalic fetuses: 1) the alpha subunit existed at each stage studies; 2) the reaction induced by anti-pLHbeta and anti-hFSHbeta sera was alwys very weak regardless of sex or age; 3) the thyrotropic cells were more numerous in comparison to the gonadotropic cells. These data are discussed in terms of the relationship of the hypophysiotropic hypothalamic factors to the appearance and evolution of the glycoprotein hormones and their subunits.

Anencephaly↗