Search PubMed⌕ Search

Biomedical subjects

E Stark

Publications and source records attributed to E Stark.

At least 109 records · Page 6Linked to original sources

Inhibition of the stimulatory effect of ACTH on adrenal and ovarian blood flow by indomethacin in the dog.

In anoestrous dogs heated thermocouples were inserted into one of the adrenals and ovaries. The basal adrenal and ovarian blood flow was recorded and enhanced by 1.2, 2.5 or 5.0 micrograms/kg of intravenous ACTH before and after the intravenous administration of 20 or 50 mg/kg of indomethacin. Indomethacin, depending on the dose and on the time elapsing after its administration inhibited the enhancing effect of ACTH on adrenal and ovarian blood flow. Since indomethacin is a specific inhibitor of prostaglandin synthesis it has been suggested that prostaglandins act as mediators in the vasodilatation elicited by ACTH in the canine adrenal and ovary.

Adrenal Glands↗

ACTH release after tuberal electrical stimulation in rats with various cuts around the medial basal hypothalamus.

After the combined treatment with dexamethasone, morphine and pentobarbitone, the electrical stimulation in the rat tuber cinereum induces a rise in plasma corticosterone (CS) level, probably by direct stimulation of the corticoliberin-producing neural elements and the consecutive ACTH release. We have attempted to locate these corticoliberin-containing neural elements by electrical stimulation in rats with various surgical cuts (deafferentations) around the medial basal hypothalamus (MBH). Seven to eight days after the complete circumsection of the MBH, the electrical stimulation of the isolated region did not affect plasma CS level. Also, the electrical excitation proved to be ineffective after antero-lateral or only lateral sections that interrupted the fibers running through the lateral region of the retrochiasmatic area. In contrast, a rise in CS level followed electrical stimulation of rats with anterolateral transections, provided the basal part of the lateral retrochiasmatic area stayed intact. We suggest that fibers traversing the basal region of the lateral retrochiasmatic area have a major role in the release of corticoliberin from the median eminence (ME).

Adrenocorticotropic Hormone↗

Possible role of gamma-aminobutyric acid synthesis in the mechanism of dexamethasone feedback action.

Specific inhibition of glutamic acid decarboxylase (GAD, EC 4.1.1.15; the main enzyme involved in the synthesis of gamma-aminobutyric acid) by mercaptopropionic acid interferes with the effect of dexamethasone on both the resting and stress-induced secretion of ACTH. It is postulated that dexamethasone may, at least in part, inhibit the secretion of ACTH via the induction of GAD, thereby raising the level of gamma-aminobutyric acid in the central nervous system.

3-Mercaptopropionic Acid↗

Evaluation of a radioimmunoassay for plasma adrenocorticotrophin.

A radioimmunoassay for plasma ACTH has been described and evaluated. Rabbit antiserum produced by immunization with [Asp25, Ala26, Gly27,]-alphah-corticotrophin-(1--28)-octacosa-peptide (a sequence analogue of alphah1--28-ACTH) bovine gamma globulin conjugate was used. The antiserum is specific for the NH2-terminal portion of the ACTH molecule and cross-reactivity of human, porcine and rat ACTH in the system has been demonstrated. Reasonable agreement was found between estimates obtained by bioassay and radio-immunoassay of the ACTH content of rat pituitary gland incubation media, indicating a close relationship between the sequence of ACTH recognized by the antibodies and the sequence possessing the steroidogenic activity. Measurement of the amount of ACTH in the plasma required the preliminary extraction and concentration of the hormone. Over a range of concentrations between 3.5 and 3600 pg/ml, extraction recovery was independent of the initial concentration of ACTH in the plasma. Extraction gave rise to no changes in the immunological properties of standard ACTH. The concentration of immunoreactive ACTH in rat plasma was 48 +/- 3.6 (S.E.M.) pg/ml in the morning and 106 +/- 9.9 pg/ml in the afternoon. Exposure to either for 5 min and subsequent laparotomy gave rise to a significant increase in the concentration of immunoreactive ACTH in the plasma. The resting level of ACTH and the ACTH response to stress were both significantly higher 1 and 7 days after adrenalectomy. Intravenous injection of a hypothalamic extract elicited a considerable rise in the concentration of immunoreactive ACTH in the plasma, but no response was seen after oral administration of this partially purified extract. The sensitivity, precision and specificity of this ACTH radioimmunoassay make it a useful tool for studying pituitary--adrenal physiology.

Adrenocorticotropic Hormone↗

Corticoliberin (CRF) activity of the rat neurohypophysis.

Corticoliberin (CRF) activity of the rat stalk-median eminence region (SME) and neural lobe of the pituitary (NL) was tested in vitro using cultured cells of anterior pituitary. The activity of NL was found to be more than 50% lower than that of SME. The parallelism of dose-response curves suggests that corticotropin releasing substances originating from NL and SME may be qualitatively identical. Thus, neurosecretory cells producing corticoliberin seem to form a continuous neurohemal system consisting of the median eminence, the stalk of the neural lobe.

Adrenocorticotropic Hormone↗

Basal levels of pituitary ACTH and plasma corticosterone after complete or frontal cuts around medial basal hypothalamus.

Plasma corticosterone level and corticotropin (ACTH) content of the anterior pituitary (AP) were measured after various cuts around the medial basal hypothalamus (MBH). Seven to eight days after placing a complete cut around MBH there was no change in plasma corticosterone or ACTH content of AP; the slight rise in ACTH concentration was offset by the decreased weight of AP. Twenty eight days after a frontal cut there was no change in plasma corticosterone and in bioactive or immunoreactive ACTH concentration of AP.

Adrenocorticotropic Hormone↗

Preparation and assessment of antisera to ACTH.

Antisera to ACTH were produced in rabbits injected repeatedly at multiple intradermal sites with synthetic [Asp25, Ala26, Gly27]alphah-corticotropin-(1-28)-octacosapeptide-bovine gamma globulin conjugate (octacosapeptide is a sequence analogue of alphah1-28-ACTH). Antibodies to extracted human or porcine ACTH were detected in all of the sera 1 month after immunization. A considerable proportion of the antisera obtained from a single final bleeding 5 months after the primary immunization were suitable for sensitive radioimmunoassay. The antisera were shown to neutralize the steroidogenic activity of ACTH in an isolated rat adrenal cell bioassay system. Titres estimated from antiserum dilution curves and relative avidities from the standard curves were compared. It was possible to detect picogram amounts of ACTH in plasma-free medium with the best antisera. The method described is an effective means of producing anti-sera to the weakly immunogenic N-terminal fragment of the ACTH molecule.

Adrenal Glands↗

Microspectrophotometry of mitochondrial cytochrome P-450 in single adrenal cells.

The cytochrome P-450 is known to be a key enzymic component in steroid hydroxylation. Biochemically it is localized in adrenal cells, both in the mitochondrial and in the microsomal fractions. Owing to its characteristic light absorptivity, attempts were made at its localization and measurement in a microspectrophotometric system. Specific difference spectra were obtained in the cytoplasm of some cells from an adrenal cell suspension before and after saturation with carbon monoxide. Scanning at 450 nm showed slender absorption maxima after CO saturation randomyl distributed in the cytoplasm. These may be attributed to mitochondria or larger cytoplasmic functional units including mitochondria.

Adrenal Glands↗

The effects of cholinomimetic drugs and atropine on ACTH release.

Acetylcholine (1 and 50 mug), carbamylcholine (1 and 10 mug), and oxotremorine (10 mug) were infused into the 3rd ventricle of rats with deafferented medial basal hypothalamus (MBH); infusions failed to stimulate ACTH release as shown by the plasma corticosterone level. Implants of an atropine-fluorescein mixture (200-250 mug) inhibited the stress-induced rise of plasma corticosterone only when dye from the implant stained large portions of the median eminence and the basal hypothalamus. Atropine implants near the electrodes inhibited the rise in plasma corticosterone usually produced by electrical stimulation in the anterior hypothalamus. Atropine crystals or a 2% atropine sulphate solution placed on the median eminence blocked conduction of action potential in the hypothalamo neurohypophyseal and tubero-infundibular pathways. The evidence will be discussed for and against the participation of a cholinergic synapse (in the MBH) that activates ACTH release after stressful neural stimuli.

Acetylcholine↗

Hypothalamic region and pathways responsible for adrenocortical response to surgical stress in rats.

Surgical stress produced no increase in the plasma corticosterone level in rats with complete deafferentation of the medial basal hypothalamus (MBH). 30 min after surgical stress, the adrenocortical response depended on the integrity of a well-circumscribed region of the hypothalamus: the lateral-basal region of the retroachiasmatic area (RCAL) that lies not more than 0.5 mm caudally from the optic chiasma and is about 0.2 mm high. One week after transsection of this region, surgical stress produced no elevation of plasma corticosterone; the effect of the operation was independent of whether various combinations of other regions and pathways to the MBH were left intact. In contrast, high plasma corticosterone levels were found after surgical stress with all kinds of hypothalamic deafferentation when the basal region of the RCAL was not transected. The possible origin of neuronal fibres running through the RCAL is discussed.

Animals↗

Competitive protein binding assay of oestradiol-17 beta and oestrone using uterine cytosol prepared from HCG-treated rabbits.

Uterine cytosol was prepared from rabbits after treatment with human chorionic gonadotrophin (HCG) and used for the determination of oestradiol-17 beta and oestrone by competitive protein binding (CPB) assay. The so obtained uterine cytosol gave higher percentage of binding and proved to be more stable when stored at --20 degrees C than cytosol obtained from the pregnant uterus.

Animals↗

Effect of cortexolone on the feedback action of dexamethasone.

Cortexolone in a dose of 1 mg/100 g body wt., administered to rats prior to dexamethasone, prevented dexamethasone from suppressing stress-induced ACTH-release without interfering with the effect of dexamethasone on the resting plasma corticosterone level.

17-Hydroxycorticosteroids↗

Changes in the fine structure and function of a hormone-secreting adrenocortical tumour investigated in tissue culture.

Tissue cultures of a surgically removed adrenocortical tumour causing Cushing's syndrome, and tissue cultures from the attached, tumour-free adrenal were studied. There were two cell types characteristic of tumour tissue. The cell type occurring most frequently had pronounced hypertrophied agranular endoplasmic reticulum. A fewer number of lipid-rich cells containing many electron-dense granules could also be found. The ratio of cells changed during cultivation. In the 17 days tumour culture, a higher percentage of lipid-rich cells could be observed. In spite of continuous ACTH treatment, the initially high hydrocortisone level decreased, gradually. It may be assumed that the lipid-rich cells are of reduced ability as regards hydrocortisone production.

Adrenal Gland Neoplasms↗

Autoradiographic localization of 3H-gamma-aminobutyric acid in the medial hypothalamus.

Tritium labelled gamma-aminobutyric acid (3H-GABA) was infused into the third ventricle of rats with normal or deafferented hypothalamus and the distribution of the label was studied by light and electron microscopic autoradiography. In control as well as deafferented hypothalamus a few neurones accumulated radioactivity, while the majority was unlabelled. Characteristic clusters and rows of silver grains were observed in the neuropil of several regions probably indicating labelled cell processes and terminal axons. Electron microscopy showed that at least some of the clusters were over axon terminals with synaptic vesicles. 3H-GABA accumulated also in the ependyma and glial elements. The results suggest that in the medial hypothalamus there is a preferential uptake of GABA in some neurones and nerve fibers; at least some of these are hypothalamic interneurones. This supports the hypothesis that some hypothalamic neurones and nerve endings may use GABA as a transmitter.

Alanine↗