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Biomedical subjects

D T Krieger

Publications and source records attributed to D T Krieger.

At least 91 records · Page 5Linked to original sources
PubMed1979

Pituitary hormones in brain: where, how, and why?

Peptide and protein hormones usually considered as being of pituitary origin have been detected within the central nervous system by means of radioimmunoassay, bioassay, and immunocytochemical techniques. Intracerebral administration of some of these hormones or fragments thereof elicit behavioral responses, suggesting that they may have a physiological role similar to that described for other peptidergic neurotransmitter or neuromodulator substances. Evidence available for some of these hormones indicates that they are synthesized within the central nervous system and that their regulation may differ from that of their pituitary counterparts.

Adrenocorticotropic Hormone↗
PubMed1979

Preliminary characterization of in vitro synthesized hypothalamic precursor ACTH/beta-endorphin-like material.

We have previously shown that cultured bovine pituitary or hypothalamic cells incorporate 3H-labeled amino acids into high molecular weight glycoproteins containing the antigenic determinants of both corticotropin (ACTH) and beta-endorphin. We now report resolution of this 3H-labeled ACTH/beta-endorphin-like material into two predominant size classes upon SDS polyacrylamide-gel electrophoresis with apparent molecular weights (Mr) of 41 500 +/- 1600 and 36 000 +/- 1100. Isoelectric focusing revealed these components to be basic proteins with apparent isoelectric points greater than 8.5. Overnight trypsinization generated a 3H-labeled fragment comigrating with synthetic beta-lipotropin (61-69) [beta-endorphin (1-9)] upon paper electrophoresis which was immunoprecipitable with antibody directed against the corresponding synthetic fragment. Limited trypsinization of bovine immunoreactive ACTH/beta-endorphin extracted from freshly obtained bovine hypothalamic and anterior pituitary tissue, generated fragments which possessed ACTH bioreactivity. Both bovine pituitary and hypothalamic derived material are similar with respect to these foregoing physiochemical parameters and appear to be larger than the reported forms in mouse pituitary.

Adrenocorticotropic Hormone↗
PubMed1979

Pituitary tumors associated with hyperprolactinemia and polycystic ovarian disease.

Galactorrhea and hyperprolactinemia, or both, have been described in some patients with polycystic ovarian disease. Three patients who had had previous bilateral wedge resection of the ovaries and who manifested persistent amenorrhea were found to have elevated levels of serum prolactin (180 to 540 ng/ml) 5 to 10 years later. All three patients initially demonstrated moderate hirsutism and failed to experience withdrawal bleeding after administration of progesterone or clomiphene citrate. Polytomographic evidence suggestive of an intrasellar tumor was present when elevated serum prolactin levels were noted. (Routine sellar roentgenograms prior to wedge resection had been reported as normal.) Two of the three patients underwent transsphenoidal surgery with removal of an 8-mm diameter chromophobe adenoma in each instance. Although serum prolactin levels decreased to 32 and 102 ng/ml, respectively, amenorrhea has persisted with gradual cessation of galactorrhea over a 1- to 2-year follow-up period. Our experience with the reported three cases supports the conclusion that in some cases an association may exist between polycystic ovarian disease and prolactin-producing adenomas.

Adult↗
PubMed1979

Biosynthesis in vitro of immunoreactive 31,000-dalton corticotropin/beta-endorphin-like material by bovine hypothalamus.

Enzymatically dispersed bovine hypothalamic or cortical tissue was maintained in culture in the presence of (3)H-labeled amino acids. After such incubation, extracts of cells and of media contained (3)H-labeled products that were specifically bound by immobilized affinity-purified antisera to corticotropin (ACTH) and beta-endorphin. The majority of these products eluted in the void volume (V(0)) upon Sephadex G-50 gel filtration; minor (3)H-labeled products eluted in the regions of the ovine beta-lipotropin marker and in fractions having apparent molecular weights of approximately 12,000 and 3800. Sequential use of these immobilized antisera revealed that most of the V(0) material contained both ACTH and beta-endorphin antigenic determinants within the same molecule(s), whereas retarded material contained only one of the determinants. When this V(0) material was rerun on a Sephadex G-75 column, it coeluted with the 31-kilodalton precursor of both ACTH and beta-endorphin obtained from a bovine anterior pituitary extract. Thus, the high molecular weight immunoreactive ACTH/beta-endorphin-like (3)H-labeled product(s) derived from the hypothalamic culture is similar to the pituitary-derived precursor in containing the dual antigenic determinants and in its gel filtration characteristics. In contrast, the cortex-derived cell preparation was devoid of (3)H-labeled products specifically reactive with the antisera employed.

Adrenocorticotropic Hormone↗
PubMed1979

Adrenocorticotropin and beta-lipotropin in the hypothalamus. Localization in the same arcuate neurons by sequential immunocytochemical procedures.

Adrenocorticotropin and beta-lipotropin (beta-LPH) have been localized by immunoperoxidase methods in nerve cells and fibers of the hypothalamus and brain stem of the ewe. 6-mum sections were immunostained first for either ACTH or beta-LPH. The reaction products and the antibody complexes were then eluted completely from the tissue, and the same section was immunostained for the second peptide. Absorption of the primary antisera with a variety of peptide fragments of ACTH and beta-LPH demonstrated, immunocytochemically as well as by radioimmunoassay, that the ACTH and beta-LPH antisera were directed to the COOH- and NH(2)-termini of the peptides, respectively. Neither antiserum recognized any portion of the heterologous peptide. In the sequential staining procedure on the same tissue section, preincubation of the antisera with the homologous peptide abolished the staining, whereas preincubation with the heterologous peptide did not affect it, regardless of the order followed. Every nerve cell in the arcuate nucleus that contained ACTH also contained beta-LPH, but beta-LPH cells appeared, probably falsely, to be twice as numerous as ACTH cells. beta-LPH-positive fibers in and beyond the hypothalamus were also more numerous and stained more intensively than ACTH fibers. The salient exception was fibers in the infundibular zona externa, where the opposite was true. Our observations establish that ACTH and beta-LPH are contained in the same nerve cells They stongly favor biosynthesis in brain, probably from a common precursor molecule, as has been demonstrated in the pituitary gland. The complexity of the cytologic distribution pattern described suggests that the two peptides are not processed in the same manner by the nerve cell.

Adrenocorticotropic Hormone↗
PubMed1979

Effect of stress, adrenocorticotropin or corticosteroid treatment, adrenalectomy, or hypophysectomy on hypothalamic immunoreactive adrenocorticotropin concentrations.

Despite variations in plasma and/or pituitary ACTH concentrations, no changes in median eminence or medial basal hypothalamic immunoreactive ACTH-like concentrations were seen in rats studied 6 weeks posthypophysectomy, 12 h or 28 days after bilateral adrenalectomy, 6 days after implantation of corticosterone pellets (75 mg), after dexamethasone administration (300 micrograms/100 g BW, ip, twice daily for 4 days), or after chronic immobilization stress. The lack of concordant variation of brain, pituitary, and plasma ACTH concentrations further supports the suggestion of a nonpituitary, central nervous system origin of some portion of brain immunoreactive ACTH-like activity.

Adrenal Cortex Hormones↗
PubMed1978

beta-Endorphin is not detectable in plasma from normal human subjects.

beta-Endorphin is not detectable in plasma from normal human subjects when measured under baseline conditions or after the subjects have received vasopressin, an agent that elevates beta-lipotropin and adrenocorticotropic hormone (ACTH). Significant amounts of beta-endorphin are present in plasma of patients with endocrine disorders associated with increased ACTH and beta-lipotropin production. Highly purified, natural beta-lipotropin is not peripherally converted to beta-endorphin in vivo in normal subjects.

Addison Disease↗
PubMed1978

beta-Lipotropin in brain: localization in hypothalamic neurons by immunoperoxidase technique.

beta-Lipotropin (beta-LPH) has been localized in hypothalamus and pituitary of sheep and ox by the immunoperoxidase technique. In both species beta-LPH was found in perikarya of arcuate neurons as well as in cells of the anterior and intermediate lobes of the pituitary. A large number of immunoreactive axons were found in the arcuate region; some appeared to innervate other neurons and others projected to portal capillaries. Stained fiber segments were also scattered throughout the hypothalamus. The presence of beta-LPH in hypothalamic neurons supports the possibility that brain beta-LPH may be a precursor for opiate-like or other peptides which may be involved in neuromodulation or neurohormonal activities.

Animals↗
PubMed1978

Comparison of synchronization of circadian corticosteroid rhythms by photoperiod and food.

Under conditions of feeding at will and normal light-dark alternation, rats consume the major portion of their daily food intake during the dark period and the circadian peak of plasma corticosteroid concentrations and of body temperature levels occurs just prior to or subsequent to the time of light-dark transition. Both light-dark transition and time of food presentation have been implicated as "Zeitgebers" in determining the phase of these two circadian rhythms. THE PRESENT DATA INDICATE THE FOLLOWING: (i) The time of food presentation appears to be a more potent synchronizer of the phase of plasma corticosteroid levels than is the light-dark cycle. This has been demonstrated in rats under conditions in which light-dark phase shift has been dissociated from a concomitant shift of time of eating. In contrast, under such conditions, the rhythm of body temperature appears to be more tightly coupled to the light-dark cycle. This illustrates that the time of food ingestion and the peak of body temperature rhythms can be uncoupled and that the phasing effects of restricted food ingestion on corticosteroid rhythms does not extend to body temperature rhythms. It also suggests the presence of different control mechanisms and/or pathways for corticosteroid and body temperature rhythms as well as the use of different pathways by different Zeitgebers. (ii) Rats maintained in constant dim light with free access to food exhibit aperiodic feeding behavior; plasma corticosteroid concentrations and body temperature levels are also aperiodic. Imposition of a restricted period of food access under such constant light conditions is associated with the appearance of a circadian periodicity of both plasma corticosteroid concentrations and body temperature levels, with peaks, respectively, just before and after the time of food presentation. This represents an additional example of food entrainment of previously aperiodic functions, similar to the food entrainment we have described in animals rendered aperiodic by lesions of the suprachiasmatic nucleus.

Adrenal Cortex Hormones↗
PubMed1978

beta-Lipotropin is the major opioid-like peptide of human pituitary and rat pars distalis: lack of significant beta-endorphin.

beta-Lipotropin is the predominant opioid peptide of the human pituitary and rat pars distalis and is present in concentrations essentially equimolar with corticotropin. When freshly, obtained nonfrozen rat anterior pituitaries were homogenized with 0.2 M HCl, approximately 98% of the immunoreactivity detected utilizing an antiserum that crossreacts equally with beta-lipotropin and beta-endorphin coeluted with 125I-labeled human beta-lipotropin upon molecular sieve chromatography. The remainder of the activity eluted with synthetic human beta-endorphin. Similar results were obtained for human pituitary. HCl homogenization of thawed tissue or homogenization of fresh tissue with acetic acid yielded substantially greater concentrations of beta-endorphin and decreased concentrations of beta-lipotropin. In human subjects, acute anterior pituitary stimulation using either insulin-induced hypoglycemia or vasopressin administration was associated with increased plasma beta-lipotropin and corticotropin levels. At the time of peak concentrations, no significant levels of beta-endorphin were detectable. These data indicate the lack of significant amounts of beta-endorphin in human pituitary. Additionally, there appears to be no specific intrapituitary conversion of beta-lipotropin to beta-endorphin.

Adrenocorticotropic Hormone↗