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Biomedical subjects

D T Krieger

Publications and source records attributed to D T Krieger.

At least 37 records · Page 2Linked to original sources

Immunoreactive corticotropin-releasing factor is present in human maternal plasma during the third trimester of pregnancy.

Immunoreactive (IR) corticotropin-releasing factor (CRF)-like activity was detectable in the majority of plasma samples obtained from women in the third trimester of pregnancy (68.7 +/- 23.6 pg/ml (14.4 +/- 4.9 fmol/ml); mean +/- SE, n = 15), but not in plasma (less than 10 pg/ml) from first (n = 9) or second (n = 11) trimester of pregnancy, 1 day post partum (n = 7), non-pregnant women (n = 10), or in plasma obtained from patients with Cushing's disease (n = 2) or Nelson's syndrome (n = 1), or in basal (n = 6) or ether-stressed (n = 6) rat plasma. Gel filtration of third trimester pooled plasma revealed that the majority of such material eluted with Kav of rat CRF (1-41). The IR CRF (1-41)-sized material eluted with the identical retention time as rat CRF in a reverse phase high performance liquid chromatography (HPLC) system. The detection of IR CRF exclusively in third trimester maternal plasma, together with our previous demonstration that material physicochemically indistinguishable from it is present in human term placental extracts, suggests that the placenta may be the source of plasma IR CRF.

Adult↗

Brain peptides.

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Adaptation, Psychological↗

Demonstration of in vivo synthesis of pro-opiomelanocortin-, beta-endorphin-, and alpha-melanotropin-like species in the adult rat brain.

An in vivo labeling technique was utilized to demonstrate the in situ biosynthesis of pro-opiomelanocortin (POMC)-, beta-endorphin- and alpha-melanotropin (MSH)-like molecular species in rat brain. Unrestrained adult female rats were bilaterally cannulated in the hypothalamic arcuate nuclear region; [35S]methionine was infused either over a 15-min period with sacrifice 2 hr subsequently, or at a constant rate for 6 hr prior to sacrifice. Sequential immune-affinity chromatography and several chromatographic and electrophoretic techniques were employed to detect and characterize POMC-related material in the hypothalamic arcuate nuclear region, preoptic area, and median eminence. Four molecular species containing both corticotropin (ACTH) and beta-endorphin antigenic determinants within the same molecules were detected in the arcuate nuclear region and preoptic area. Two forms were similar to rat pituitary POMC with respect to apparent molecular weight (35,000 and 31,500) and [35S]methionine-containing tryptic fragments (one methionine each in N-terminal glycopeptide, ACTH, and beta-endorphin sequences of rat POMC). The other two forms (apparent Mr of 21,000 and 19,000) contained only the labeled tryptic fragments characteristic of ACTH and beta-endorphin. The detection of the latter forms suggests that POMC in brain, unlike its post-translational processing in rat pituitary, undergoes primary cleavage between the N-terminal peptide and the ACTH sequence. Peptides physicochemically indistinguishable from authentic beta-endorphin and des-acetyl alpha-MSH were detected in approximately equimolar amounts in all three brain regions. The ratio of POMC-like material to the alpha-MSH- and beta-endorphin-sized peptides was highest in the arcuate nuclear region, suggesting that POMC-like proteins are synthesized in the arcuate nuclear region and are processed into the smaller molecular species during axonal transport.

Animals↗

Brain peptides: what, where, and why?

Within the past decade, a large number of peptides have been described within the vertebrate central nervous system. Some of these peptides were previously known to be present in nonneural vertebrate tissues, as well as in lower species, in which they may serve as primitive elements of intercellular communication prior to the development of neuronal or endocrine systems. In vertebrates, these peptides are thought to have neurotransmitter or neuromodulatory roles and appear to be involved in the regulation of a number of homeostatic systems, although the mechanisms of their actions are still unclear.

Animals↗

DST in depression is unaffected by altering the clock time of its administration.

Circadian oscillators in major depressive illness may be phase advanced by several hours. We attempted to determine whether phase advance of the oscillator responsible for hypothalamic-pituitary-adrenal (HPA) function in depressives might influence the outcome of the overnight dexamethasone suppression test (DST). Six major depressives underwent DST with dexamethasone doses administered in a randomized fashion at 1900h and 2300h on separate evenings. Twenty-four hour cortisol secretory patterns basally and postdexamethasone were obtained for each subject. Postdexamethasone cortisol responses were similar for both the 1900h and 2300h dosage schedules in suppressors, nonsuppressors, and an early escape responder. We conclude that failure of the HPA axis to suppress normally with DST in major-depressive illness is a primary feature of neuroendocrine regulatory mechanisms rather than secondary to a posited phase advance of the related circadian oscillator.

Aged↗

Serotonin immunoreactive nerve fibers and terminals in the rat pituitary--light- and electron-microscopic studies.

Serotonin-immunoreactive nerve fibers were demonstrated to form a plexus in the intermediate lobe of rat pituitary. Such fibers were sporadic in the posterior lobe where they occurred exclusively in the zone adjacent to the intermediate lobe, and in the anterior lobe. With the aid of electron-microscopic immunocytochemistry, labeled fibers were shown to constitute the majority of neuronal processes found in the intercellular region of the intermediate lobe. They were frequently seen to establish synaptoid contacts with endocrine cells.

Animals↗

Plasma immunoreactive beta-endorphin is elevated in uraemia.

Plasma immunoreactive-(IR) beta-endorphin (beta-EP) and beta-lipotrophin (beta-LPH) levels were measured in 15 adult uraemic patients on chronic haemodialysis. The presence of immunoreactivity eluting in the position of beta-EP was demonstrated following submission of pooled extracts of uraemic plasma to gel permeation chromatography on Sephadex G-50. To separate beta-EP from beta-LPH, pre-dialysis plasma extracts from six individual patients, and three pools of three patients each, were submitted to sequential immune-affinity chromatography and levels were measured by radioimmunoassay. In all cases, plasma IR beta-EP concentrations were markedly increased compared with normal subjects (m +/- SEM fmol/ml; 64.4 +/- 13.7 vs. 2.3 +/- 0.2). IR beta-LPH concentrations were also increased (m +/- SEM fmol/ml; 55.7 +/- 13.2 vs. normal 6.1 +/- 0.8). In addition, post-dialysis concentrations of plasma IR beta-EP and beta-LPH were lower than pre-dialysis levels (n = 4).

Adult↗

Brain tissue grafts in the central nervous system: reversal of hypogonadism.

Transplantation of brain tissue from normal donors into the central nervous system of animals with specific central neurochemical deficiencies has been used to remedy such defects. The present studies demonstrate that the hypogonadism present in the adult male hypogonadal (hpg) mouse that is secondary to hypothalamic gonadotropin releasing hormone (GnRH) deficiency can be corrected by grafts into the anterior third ventricle of fetal preoptic area (p.o.a.) tissue. The p.o.a. is a primary site of localization of GnRH neurones in rodents. As compared with untreated hpg males, or with hpg males that had received control cortical tissue implants, the hpg animals with p.o.a. grafts showed measurable levels of GnRH within the hypothalamus. Immunocytochemical studies revealed GnRH within the transplants. Increased pituitary and plasma LH and FSH, and testicular growth with full spermatogenesis, were also evident in the hpg males that had received p.o.a. implants.

Animals↗

Serotonergic innervation of the rat pituitary intermediate lobe: decrease after stalk section.

Serotonin (5-HT)-containing nerve fibers and terminals, but not cell bodies, have been demonstrated by light and electron microscopic immunocytochemistry in the intermediate lobe of the rat pituitary. Seven days after pituitary stalk transection, 5-HT immunoreactive fibers disappeared almost entirely from the intermediate lobe. Intermediate lobe 5-HT and 5-hydroxyindoleacetic acid concentrations, measured by high pressure liquid chromatography coupled to electrochemical detection, fell to 56% and 62% of control, respectively. There were no changes in 5-HT concentrations in anterior or posterior lobes of the pituitary or in the median eminence. These findings, and the failure of sympathectomy to cause a drop in pars intermedia 5-HT, indicate that in the intermediate lobe of the pituitary neuronal 5-HT originates in cells situated in the central nervous system.

Animals↗

Characterization of immunoreactive proopiomelanocortin-related peptides in rat testes.

alpha-Endorphin, beta-endorphin, gamma-endorphin, and N-terminal ACTH immunoreactivity were detectable in acid extracts of rat testes with concentrations of 0.07 +/- 0.01, 0.18 +/- 0.03, 0.06 +/- 0.01, and 0.33 +/- 0.08 (+/- SD) pmol/g wet wt, respectively. The forms of these immunoreactive peptides were characterized by reverse phase high performance liquid chromatography. Immunoreactive beta-endorphin was also analyzed by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The results indicated that the major form of immunoreactive beta-endorphin present appears to be beta-endorphin-(1-31). No alpha-N-acetylated forms of beta-endorphin or beta-lipotropin-sized material were detected. Immunoreactive alpha- and gamma-endorphin appear to be present as alpha-endorphin and des-Tyr1-gamma-endorphin, respectively. Immunoreactive alpha MSH was present as its desacetylated form. No immunoreactive ACTH fractionating with ACTH-(1-39) or its glycosylated forms was detected. This peptide profile is most similar to that seen for proopiomelanocortin-derived peptides in the brain. The low concentrations of these peptides in rat testes suggest a paracrine function.

Adrenocorticotropic Hormone↗

Are messenger molecules in microbes the ancestors of the vertebrate hormones and tissue factors?

Peptides very similar to hormones and other messenger molecules of vertebrates have been detected in extracts of unicellular eukaryotes (and prokaryotes). We present arguments to suggest the possibility that these molecules 1) originated evolutionarily in unicellular microbes, 2) serve as intercellular messenger molecules in these organisms, and 3) represent the phylogenetic ancestors of the hormones and neurotransmitters as well as paracrine and other tissue factors of the vertebrates. We suggest that the biochemical elements of intercellular communication arose very early in evolution and are highly conserved; evolution largely changed the anatomy, i.e., the nature of the secretory cell, the target cell, and the fluid compartment that carries the messenger molecule from one to the other. Such an approach suggests a more rational relationship between different modes of intercellular chemical signaling in vertebrates.

Animals↗

The hormonal and cellular control of Sertoli cell secretion.

Sertoli cells synthesize and secrete a number of cell-specific products including androgen binding protein (ABP), as well as "serum proteins" such as transferrin. The secretion of these proteins is regulated by extra-testicular hormones such as FSH and insulin; Leydig cell-produced steroids and proopiomelano-cortin-derived peptides; and the presence of peritubular myoid cells and/or factors secreted by these cells. Many of the Sertoli cell proteins are secreted in a cyclic fashion during the different stages of the spermatogenic cycle suggesting communication between Sertoli cells and developing germ cells. The availability of quantitative measurements for Sertoli cell-specific proteins such as ABP make it feasible to follow Sertoli cell function in vivo by measuring these products in serum. A bidirectional secretion of proteins by Sertoli cells is proposed to explain the presence of specific peptides in the male reproductive tract and blood.

Androgen-Binding Protein↗

Brain grafts reverse hypogonadism of gonadotropin releasing hormone deficiency.

Hypogonadism in the mutant hpg mouse is characterized by a deficiency of hypothalamic gonadotropin releasing hormone (GnRH). Affected male mice exhibit immature reproductive organs, small abdominal testes and low pituitary and plasma gonadotropin concentrations. Recent studies have demonstrated the potential of fetal brain transplants to establish functional connections with host tissues. We therefore sought to use this approach to correct the hpg deficit. Fetal preoptic area (POA) (a site of GnRH production) from unaffected animals of the hpg strain was transplanted into the anterior third ventricle of adult hpg mice. We report that in such implanted animals, killed 2 months post-implantation, the POA grafts contained GnRH neurones, from which GnRH-positive fibres could be traced to capillaries of the median eminence. Hypothalamic GnRH and pituitary and plasma gonadotropin concentrations were increased compared with levels in untreated (hpg) animals. The testes were enlarged and had descended into the scrotum. Evidence of full spermatogenesis and interstitial cell development was present in testicular sections. No such effects were seen with transplants of cortical tissue.

Animals↗