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Biomedical subjects

D T Krieger

Publications and source records attributed to D T Krieger.

At least 55 records · Page 3Linked to original sources

Plasma beta-lipotropin levels in Parkinson's disease.

Previous reports have indicated that patients with Parkinson's disease have elevated plasma levels of immunoreactive (IR) beta-melanocyte stimulating hormone (beta-MSH), which may have implications as to its pathogenesis and treatment. Recent methodological advances, however, have demonstrated that what had originally been measured in human plasma as beta-MSH actually represents beta-lipotropin (beta-LPH), and that beta-MSH as such does not normally circulate in human plasma. With the capacity to specifically measure immunoreactive beta-LPH in human plasma, we have determined plasma levels of immunoreactive beta-LPH as well as ACTH and prolactin in three groups of subjects: A. Parkinson patients untreated with levodopa (n = 11); B. Parkinson patients on levodopa therapy (n = 21); C. Controls (n = 6). No difference was found in plasma levels of IR-beta-LPH and IR-ACTH between these three groups. Plasma levels of prolactin were not different in either group of Parkinsonian patients as compared to controls. However, prolactin levels were significantly lower in the Parkinsonian patients treated with levodopa versus the untreated group. These data suggest that there is no defect in beta-LPH release from the pituitary in Parkinson's disease.

Adrenocorticotropic Hormone↗

The effects of subdiaphragmatic vagotomy on circadian corticosterone rhythmicity in rats with continuous or restricted food access.

Plasma corticosteroid circadian periodicity was determined in three groups of individual adult male rats. Categories were: post-subdiaphragmatic vagotomy, sham-operated, and controls. Blood was sampled every 4 hours over a 48-hour period with ad lib feeding and after a 13-day period on daytime (0930--1330) restriction of food and water availability. Plasma corticosterone circadian periodicity was normal under ad lib conditions in control, sham-operated, and vagotomized animals. Under food-restricted conditions, both the sham-operated and vagotomized animals exhibited the 12-hour shift in the circadian peak of plasma corticosterone levels that we have previously described in normal animals under such conditions. There were no differences between groups in the total amount of food and water consumed or the percentage of nocturnal food intake on an ad lib feeding schedule. Both vagotomized and sham-operated animals manifested reductions in food intake under conditions of food restriction, although vagotomized consumed less than sham-operated animals. The present data indicate that an intact vagus nerve is not necessary for the establishment of circadian periodicity of plasma corticosterone levels or the shift in the periodicity of corticosteroid secretion produced by a restricted feeding regimen.

Analysis of Variance↗

Corticotropin and beta-endorphin-like materials are native to unicellular organisms.

Multiple molecular forms of immunoreactive corticotropin (ACTH) and beta-endorphin were present in extracts of a unicellular eukaryote (Tetrahymena pyriformis). One form of immunoreactive ACTH reacted similarly with two different ACTH antisera (one specific for the 11-24 sequence and the other with determinants within sequences 1-14 and 17-39) and migrated with synthetic hACTH-(1-39) in a gel filtration system. This form also exhibited ACTH bioactivity in a dispersed rat adrenal cell bioassay system, with a mean immunoassay/bioassay ratio of 1.5. Gel filtration revealed multiple size classes of immunoreactive beta-endorphin; a major peak of radioreceptor activity was detected which exhibited a K(av) similar to that of authentic beta-endorphin. A major portion of immunoreactive beta-endorphin-sized material exhibited retention times similar to those of synthetic human and camel beta-endorphin upon reverse-phase high-pressure liquid chromatography. These distinctive properties and specificities would seem to exclude the presence of limited homologies with sequences present in other proteins. High molecular weight material containing both ACTH and beta-endorphin antigenic determinants was also demonstrated, suggesting, but not proving, the presence of a common precursor molecule.

Journal Article↗

Placenta as a source of 'brain' and 'pituitary' hormones.

Placental peptides, such as human chorionic gonadotropin (hCG) and human placental lactogen (hPL), which have marked homologies to pituitary peptides, were described in the early part of this century. Recently, the presence in placenta of additional peptides previously demonstrated as occurring in other tissues, such as brain and pituitary, has been reported. Their presence in placenta has been attributed to similar embryological origin of the tissues which share these peptides, although this has by no means been proven. Placental concentrations of these recently described peptides are several orders of magnitude lower than described for their original sites of production. In many instances, definitive characterization of structural identity with their extraplacental counterparts has not been performed, but has been based on indirect evidence obtained by immunoassay or immunocytochemistry. Evidence of placental synthesis has been obtained for hCG, hPL, and pro-opiomelanocortin (the precursor molecule for adrenocorticotropic hormone (ACTH), B-lipotropin (B-LPH), alpha-melanocyte-stimulating hormone (alpha-MSH), beta-endorphin, and other thus far uncharacterized peptides). Possible functions for the recently described peptides might include actions on the maternal or fetal systems or local (paracrine) actins affecting other placental constituents, although to date no definitive physiological roles have been demonstrated.

Adrenocorticotropic Hormone↗

Specific in vitro uptake of serotonin by cells in the anterior pituitary of the rat.

In vivo studies have suggested that serotonin (5HT) influences anterior pituitary function at the hypothalamic level. The present in vitro study investigated the possibility that 5HT may act directly on the anterior pituitary. The high affinity uptake of [3H]5HT into adult rat anterior pituitary tissue was examined in two types of experiments. 1) To test the specificity and saturability of uptake of 5HT in the anterior pituitary, pituitary tissue was incubated (37 C) with [3H]5HT (10(-8)-10(-6) M) in the presence and absence of excess (10(-5) M) unlabeled 5HT, norepinephrine, fluoxetine (FLUOX), metergoline, or cyproheptadine. A Hofstee analysis of the specific uptake of [3H]5HT gave an apparent Km value of 4.23 x 10(-7) M and a Vmax of 1576 pmol/g/10 min [3H]5HT. The total uptake of [3H]5HT was not altered by norepinephrine or metergoline, but was significantly reduced (P less than 0.01-0.001) by FLUOX and cyproheptadine. Uptake was shown to be temperature and sodium dependent and not directly dependent on energy derived from glycolysis or aerobic metabolism. 2) To study the site of uptake of 5 HT in the anterior pituitary, in concomitant radioautographic experiments, tissue was incubated with [3H]5HT with and without excess 5HT or FLUOX. Three patterns of silver grain distribution were observed: 1) nonrandom concentrations over select anterior pituitary cells near blood vessels, 2) heavy aggregates of silver grains usually associated with blood vessels, and 3) a seemingly random dispersal of grains over pituitary tissue. Tissue incubated with [3H]5HT alone contained 10% heavily labeled cells, 32% moderately labeled cells, and 58% weakly labeled cells. In contrast, no heavily labeled cells were seen when tissue was incubated with either excess 5HT or FLUOX in addition to [3H]5HT. Our findings of saturable and specific high affinity uptake of [3H]5HT into a subgroup of anterior pituitary cells suggest a direct pituitary action of 5HT.

Animals↗

Failure of bromocriptine to lower plasma catecholamines in normal men and women.

A plasma catecholamine-lowering effect of bromocriptine has previously been reported in normals, but not in patients with PRL- or GH-secreting pituitary tumors, and has been used as evidence to support the concept of disordered central nervous system dopaminergic tone in patients with such tumors and as a test to distinguish them from normals. In the present study of 16 normal subjects (9 women and 7 men), we found no significant change in plasma norepinephrine or epinephrine after bromocriptine. Similarly, no change occurred in plasma catecholamines in 8 patients with PRL-secreting tumors or 6 patients with ACTH hypersecretion. Our data, therefore, do not provide confirmatory evidence for an effect of bromocriptine on plasma catecholamines in normal subjects and do not support the proposed use of bromocriptine as a test for defective central dopaminergic regulation.

Adrenocorticotropic Hormone↗

Immunocytochemical study of the hypophysis in 25 dogs with pituitary-dependent hyperadrenocorticism.

Pituitary adenomas were found in 21 (84%) of 25 dogs with spontaneous pituitary-dependent hyperadrenocorticism. Six dogs had pars intermedia adenomas, whereas 15 had tumours of the pars distalis. Diffuse corticotroph cell hyperplasia was found in 1 of the 4 pituitaries without adenoma; in 2 dogs with pituitary adenoma, coexisting hyperplasia of the surrounding corticotrophs was also present. Immunocytochemical staining of the pituitaries revealed positive staining for ACTH, beta-lipotrophin, and beta-endorphin in the majority of both pars distalis and pars intermedia adenomas. The most frequent and intense staining was found with anti-beta-endorphin. In most part intermedia tumours, many cells stained strongly for alpha-MSH; double immunostaining of one pars intermedia adenoma for ACTH and alpha-MSH showed that some tumour cells stained only for ACTH or alpha-MSH whereas others contained both peptides. Only occasional cells stained for alpha-MSH in pars distalis adenomas.

Adenoma↗

Brain peptides.

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Adrenocorticotropic Hormone↗