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Biomedical subjects

W E Stumpf

Publications and source records attributed to W E Stumpf.

At least 145 records · Page 8Linked to original sources
PubMed1984

Localization of aldosterone and corticosterone in the central nervous system, assessed by quantitative autoradiography.

Nuclear localization of tritiated aldosterone in the CNS was studied in rats by numerical evaluation of silver grains, deposited over neuronal cell nuclei in thaw-mounted autoradiograms, and compared with the localization obtained after prior administration of a 100-fold excess of radioinert aldosterone, corticosterone or 18-hydroxy-11-deoxycorticosterone (18-OH-DOC). Corticosterone and 18-OH-DOC completely prevented nuclear localization in most regions examined. However, in contrast to pretreatment with aldosterone, pretreatment with corticosterone and 18-OH-DOC did not completely prevent the concentration of radioactivity in the cell nuclei of the indusium griseum. Traces of radioactivity were, furthermore, retained in areas CA1 and CA2 and the dentate gyrus in rats exposed to corticosterone, but not to 18-OH-DOC, prior to [3H]aldosterone. A similar profile of silver grain distribution to that noted with aldosterone was found for corticosterone except that with tritiated corticosterone the most intense concentration of radioactivity occurred in hippocampal areas CA1 and CA2 and not in the indusium griseum. Prior administration of excess deoxycorticosterone acetate abolished nuclear accumulation of tritiated corticosterone. Dihydrotestosterone, on the other hand, failed to compete with tritiated corticosterone at a dose 200-fold in excess of the tritiated steroid. We conclude that (1) a receptor readily shared by aldosterone, corticosterone, 18-OH-DOC and DOC, but not by dihydrotestosterone, is widely distributed throughout the CNS, (2) a receptor shared by aldosterone and 18-OH-DOC, but not by corticosterone may be present in hippocampal areas CA1 and CA2, (3) that both these as well as the receptor accepting dihydrotestosterone can be located within the same cell.

Aldosterone↗
PubMed1984

Receptor-mediated binding and uptake of GnRH agonist and antagonist by pituitary cells.

The intracellular pathway of an enzyme resistant GnRH agonist (D-Lys6-GnRH) conjugated to ferritin or to colloidal gold was followed in cultured pituitary cells. After an initial uniform distribution over the cell surface of gonadotropes, the electrondense marker was internalized, either individually or in small groups. Some, but not all marker was associated with invaginated membrane specializations showing a proteineous coat at their cytoplasmic site. After longer incubation times, the marker appeared in the lysosomal compartment and the Golgi apparatus, where it could be found in the vesicular as well as cisternal portion. In addition, the receptor-mediated endocytosis of the GnRH antagonist D-p-Glu1-D-Phe2-D-Trp3-D-Lys6-GnRH was studied by light and electron microscopic autoradiography after 30 and 60 min of incubation to ensure uptake. At both time points, in in vitro as well as in vivo studies, silver grains were localized over cytoplasmic organelles of castration cells, including dilated endoplasmic reticulum, lysosomes, and clear vesicles. No consistent association with cell nuclei, mitochondria, or secretory vesicles could be observed. The results suggest that both agonist and antagonist are binding selectively to the plasma membrane of gonadotropes and subsequently are taken up via receptor-mediated endocytosis for degradation or possible action on synthetic processes.

Animals↗
PubMed1984

The A-B-C (Allocortex-Brainstem-Core) circuitry of endocrine-autonomic integration and regulation: a proposed hypothesis on the anatomical-functional relationships between estradiol sites of action and peptidergic-aminergic neuronal systems.

A sex steroid hormone sensitive brainstem-allocortex axis of neuronal cell groups and projections is recognized with convergent pathways of aminergic-peptidergic messenger systems, which subserves the adjustment for varying reproductive and environmental conditions and the coordination of endocrine-autonomic functions. Main stations in the A-B-C (Allocortex-Brainstem-Core) periventricular axis include the substantia gelatinosa, nucleus (n.) tractus solitarii-dorsal vagal nucleus-area postrema complex, locus ceruleus, n. parabrachialis, central gray and associated raphe nuclei, ventral tegmental area, lateral and periventricular hypothalamus, n. paraventricularis, bed nucleus of the stria terminalis, preoptic-septal nuclei and n. centralis amygdalae with associated amygdaloid nuclei, as well as the ventral and dorsal allocortex. All of these stations and their periventricular and medial forebrain bundle projections contain estradiol sites of action and represent elements of earlier defined periventricular estradiol-target neuron systems. Results from colocalization of 3H estradiol by thaw-mount autoradiography and aminergic and peptidergic messengers by immunohistochemistry or other histochemical techniques indicate direct nuclear effects of estradiol on certain noradrenalin, dopamine, gamma aminobutyric acid, somatostatin, and neurophysin neurons. Additional data about correspondence of estradiol-target neuron accumulations with neuronal sites of peptide messenger production suggest direct effects of estradiol on certain enkephalin, endorphin, corticotropin releasing hormone, adrenalin, serotonin, cholecystokinin, pancreatic polypeptide and gonadotropin releasing hormone neurons--and probably others. As documented for the pituitary, and as an approach to understand varying and dual effects, it is postulated that estradiol activation of brain messenger systems parallels the heterogeneous estradiol binding in the A-B-C- system. This is expressed in the concept of differential Multiple Activation of Heterogeneous Systems (MAHS).(ABSTRACT TRUNCATED AT 250 WORDS)

Amines↗
PubMed1983

Topographic distribution of progestin target cells in hamster brain and pituitary after injection of [3H]R5020.

The topographic distribution of progestin concentrating cells in the female hamster brain and pituitary was studied by thaw-mount autoradiography. Fifteen minutes after injection of [3H]R5020, a synthetic progestin, nuclear uptake and concentration of radioactivity was found in certain cells of the forebrain and midbrain, as well as in the anterior pituitary. Competition studies with unlabeled R5020 abolished and with progesterone reduced the nuclear uptake of radioactivity. In the forebrain, radioactively labeled cells are observed in n. septi lateralis, n. interstitialis striae terminalis, n. preopticus medialis and lateralis, n. periventricularis hypothalami, organum subfornicale, n. arcuatus hypothalami, n. ventromedialis hypothalami, n. dorsomedialis hypothalami and n. premammillaris ventralis. In the midbrain a few labeled cells are found in the griseum centrale. In the anterior pituitary, labeled cells are identified by immunostaining as luteinizing hormone-producing cells. The results of the autoradiographic study demonstrate nuclear progestin binding sites and suggest genomic action of progestin on the labeled structures, probably related to the modulation of gonadotropin secretion and sexual behavior in the brain and pituitary.

Animals↗
PubMed1983

Anatomical relationships of dopaminergic and GABAergic systems with the GnRH-systems in the septo-hypothalamic area. Immunohistochemical studies.

Immunohistochemical double staining for gonadotropin releasing hormone (GnRH) and tyrosine hydroxylase (TH) or glutamic acid decarboxylase (GAD) reveals in the septo-preoptic-diagonal band complex of the rat brain close spatial associations between GnRH-immunoreactive perikarya and TH and GAD immunoreactive fibers. In the organum vasculosum laminae terminalis, no close spatial relationships could be observed between TH- or GAD-positive fibers and the GnRH-containing system. In contrast, in the median eminence substantial overlap exists in the distribution of GnRH with TH and GAD containing nerve fibers. This overlap is most intense for TH throughout the lateral palisade zone, while for GAD it is more restricted to the outermost portion of the external palisade zone. The results suggest that dopamine and GABA influence GnRH secretion via axosomatic contacts in the septo-preoptic-diagonal band complex, as well as via axo-axonic interactions in the median eminence, while no such interactions seem to exist in the organum vasculosum laminae terminalis. Since dopaminergic cell bodies in the ventral hypothalamus are closely apposed by GnRH and GAD containing fibers, the existence of feedback circuits among GnRH, dopamine and GABA systems is proposed.

Animals↗
PubMed1983

Autoradiographic localization of target cells for 1 alpha, 25-dihydroxyvitamin D3 in bones from fetal rats.

Thaw-mount autoradiographic studies after injection of 3H-1,25-D3 were conducted on 18- and 20-day-old rat fetuses. In maxillary bones, ribs, and tibia, nuclear concentration of radioactivity was found in osteoprogenitor cells and osteoblasts. Osteocytes and chondrocytes in epiphyseal plates were either unlabeled or weakly labeled. In competition experiments, nuclear concentration of radioactivity was blocked by the injection of a high dose of nonradioactive 1,25-D3 prior to the administration of the labeled hormone, but not by a similar dose of nonradioactive 25-D3. The results are interpreted as indicating that osteoprogenitor cells and osteoblasts are target cells for the direct action of 1,25-D3 on fetal bone.

Animals↗
PubMed1983

Autoradiographic localization of 1,25-dihydroxyvitamin D3 in rat placenta and yolk sac.

After injection of 3H-1,25-(OH)-vitamin D3 into rats on days 18 and 20 of pregnancy, autoradiograms of placenta and fetal membranes show nuclear concentration of radioactivity in certain cells. This nuclear concentration is abolished when unlabeled 1,25-(OH)2-vitamin D3, but not 25-(OH)-vitamin D3, is injected prior to the labeled hormone. Nuclear labeling is observed in epithelial cells of visceral yolk sac and amnion, and in certain trophoblasts in basalis and labyrinth. The results suggest the presence of a specific receptor-like binding for 1,25-(OH)2-vitamin D3 and thus involvement of the target cells in calcium regulatory mechanisms during development.

Animals↗
PubMed1983

Target cells for 1,25-dihydroxyvitamin D3 in developing rat incisor teeth.

The concentration of radioactivity is observed in the nuclei of pulpal cells of maxillary and mandibular incisors of 20-day-old fetal rats, following injection of [3H]-1,25 (OH)2 vitamin D3. Cells in the odontoblast and ameloblast layers are essentially free of nuclear labeling. The radioactively labeled pulpal cells exist throughout the length of the incisors with the exception of the progenitor areas. The results indicate the presence of receptors for 1,25 (OH)2 vitamin D3 in pulpal cells, and suggest the effects of the hormone on these cells.

Ameloblasts↗
PubMed1983

Intracellular pathways of electron-opaque gonadotropin-releasing hormone derivatives bound by cultured gonadotropes.

A metabolically stable GnRH agonist (D-Lys6-GnRH) has been coupled to electron-opaque markers (colloidal gold and ferritin) to characterize the intracellular pathway of the releasing hormone bound by pituitary gonadotropes. This approach has the advantage of increasing the resolution of localization to a "circle of uncertainty" about 10- to 20-fold smaller than that which can be obtained by autoradiography. After an initial uniform distribution on the cell surface, the derivatives were taken up individually as well as in small clusters in coated and uncoated membrane invaginations and moved to the lysosomal compartment either directly or after passage through the Golgi apparatus. The results suggest that labeled GnRH or GnRH-receptor complex may be routed to two distinct intracellular compartments: the lysosome and the Golgi cisternae. It is unclear whether each releasing hormone-marker conjugate must be transported through both compartments before degradation.

Animals↗
PubMed1983

[The progesterone receptor in the chicken oviduct: double disclosure by immunohistochemistry with antireceptor antibodies and autoradiography with tritiated progestin].

Explants of estradiol primed Chicken oviduct were incubated with a tritiated synthetic progestin (3H-Org 2058). Frozen sections were processed either for autoradiography, or for immunohistochemistry with two different antibodies to the progesterone receptor, or, for the first time, by the two techniques combined on the same section. In all cell types (glands, luminal epithelium, stroma, mesothelium and muscle fibers) where the tritiated hormone was concentrated in the nuclei, the receptor was also recognized in the nuclei by both antibodies. In the center part of the explants, cells did not show radioactive nuclear labeling, though the nuclei displayed the same intensity of reaction with the antibodies as external cells. This result suggests the presence of progesterone receptor in nuclei of target cells even in absence of progesterone. The same combined double hormonal and immunological evidence of progesterone receptor was obtained in pituitary cells of a chicken injected with 3H-Org 2058.

Animals↗
PubMed1982

Neurotensin: topographical distribution in rat brain by immunohistochemistry.

The anatomical distribution of neurotensin perikarya and fibers in rat brain, spinal cord, and pituitary has been studied by immunohistochemistry. Neurotensin immunoreactivity is widely distributed throughout the brain, especially in forebrain and midbrain limbic structures, but also in the pons, medulla, and spinal cord. Areas with low immunoreactivity, or lack of it, stand out and include most of the hippocampus, isocortex, ventromedial and dorsomedial hypothalamic nuclei, somatomotor nuclei, cerebellum, and dorsal column nuclei. Strong neurotensin immunoreactivity is found in accumbens-caudate-putamen, central and medial amygdaloid nuclei, ventrolateral septum, pars lateralis of the nucleus of the stria terminalis, paraventricular, periventricular, and lateral hypothalamus, median eminence, thalamic intralaminar and periventricular nuclei, ventral tegmentum, central gray, certain raphe nuclei, locus ceruleus, nucleus parabrachialis medialis and lateralis, nucleus of the solitary tract and area postrema, spinal and trigeminal substantia gelatinosa, as well as certain cells in the anterior pituitary. The anatomical data suggest the existence of neurotensin circuits for (1) the control of autonomic-endocrine functions, involving the nucleus tractus solitarii, area postrema, nucleus ambiguus, nucleus parabrachialis, nucleus paraventricularis, nucleus centralis amygdalae, and pars lateralis of the bed nucleus of the stria terminalis; and (2) for the transmission and modulation of certain somatosensory qualities, involving the spinal substantia gelatinosa, trigeminal sensory nuclei, and thalamic intralaminar nuclei.

Animals↗
PubMed1982

Brain target sites for 1,25-dihydroxyvitamin D3.

Autoradiographic studies with 3H-labeled 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] demonstrate, in certain neurons of rat forebrain, hindbrain, and spinal cord, a nuclear retention and concentration of radioactivity, which can be prevented by treatment with 1,25(OH)2D3, but not with 25-hydroxyvitamin D3. These results indicate the presence of brain receptors in addition to pituitary receptors for 1,25(OH)2D3 and suggest a central modulation of calcium homeostasis and other central effects for this hormone. The existence of a brain-pituitary axis for certain 1,25(OH)2D3-mediated endocrine-autonomic effects is postulated.

25-Hydroxyvitamin D 2↗