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Biomedical subjects

D Staley

Publications and source records attributed to D Staley.

28 records · Page 2Linked to original sources
PubMed1986

Mechanism of action of gonadotropin releasing hormone.

GnRH interacts with a plasma membrane receptor to provoke gonadotropin release, as well as regulate numbers of its own receptor and target cell responsiveness. Receptor numbers are altered in different physiological states of the animal. Microaggregation of the GnRH receptor mimics all known actions of the releasing hormone, and therefore is viewed as an early step in the molecular mechanism of hormone action. Internalized hormone is neither necessary nor sufficient for stimulation of known releasing hormone actions. Evidence summarized in the present work suggests that Ca2+ serves a role as a second messenger for GnRH-stimulated gonadotropin release, and that it may be involved in receptor up-regulation in response to the releasing hormone. In the former role, diacylglycerols by their action on protein kinase C, in a fashion independent of the Ca2+ -calmodulin system, may act as a signal amplifier.

Animals↗
PubMed1985

Diacylglycerols release LH: structure-activity relations reveal a role for protein kinase C.

A series of diacylglycerols were synthesized with varying lengths and substituents in order to establish the structure-activity relationship between each with activation of protein kinase C and stimulation of a biological response system (pituitary luteinizing hormone release). This approach enables distinction between actions mediated by direct activation of protein kinase C and those due to other, presumably nonspecific, actions. The ability of diacylglycerols to function as regulators of a biological response system (pituitary luteinizing hormone release) and of protein kinase C was investigated with a series of sn-1,2 diacylglycerols containing fatty acids 4-10 carbons in length and with analogs in which the 3' hydroxyl was replaced with a chloro, hydrogen, or sulfhydryl moiety. Several diacylglycerols stimulated LH release in a saturable, time and dose dependent manner that was independent of extra-cellular calcium. Dioctanoylglycerol (diC8) was the most effective of the diacylglycerols tested; 3' analogs lacking the hydroxyl were inactive. The diacylglycerols activated protein kinase C in vitro whereas the 3' analogs did not. These data implicate protein kinase C in the mechanism of LH release, demonstrate that unsaturated fatty acyl moieties within the diacylglycerol are not required for protein kinase C activation, and establish diacylglycerol-protein kinase C structure-function relationships that should prove useful for investigations in other systems.

Animals↗
PubMed1985

Molecular mechanism of gonadotropin releasing hormone action.

This work summarizes some of our studies related to the mechanism of action of gonadotropin releasing hormone including those leading to identification of the three steps of the gonadotropin releasing process: receptor binding, mobilization of extracellular calcium, and granule exocytosis. Evidence is also presented to suggest how these steps are integrated one to another and how they are integrated to other actions of the releasing hormone such as regulation of target cell sensitivity, and receptor regulation.

Animals↗
PubMed1985

Diacylglycerols and protein kinase C. Potential amplifying mechanism for Ca2+-mediated gonadotropin-releasing hormone-stimulated luteinizing hormone release.

The present study was designed to test the hypothesis that there is a functional interaction between the calcium-calmodulin system, which appears to mediate the action of gonadotropin-releasing hormone (GnRH), and activators of protein kinase C, which stimulate luteinizing hormone (LH) release by a mechanism which does not require extracellular calcium. We have examined a diacylglycerol and a phorbol ester, which both activate protein kinase C and stimulate LH release. These compounds show synergistic action with calcium ionophore A23187 as secretogogues. Pimozide (a calmodulin antagonist), methoxyverapamil (a calcium ion channel inhibitor), and Ac[D-pCl-Phe1,2-D-Trp3-D-Lys6-D-Ala10]GnRH (a potent gonadotropin-releasing hormone antagonist) were used to show that the diacylglycerol and phorbol ester can stimulate LH release in a manner that is independent of both Ca2+ and calmodulin and do not work by means of a direct action on the GnRH receptor. These observations, coupled with previously published reports that extracellular Ca2+ mobilization is both necessary and sufficient for initiation and perpetuation of GnRH-stimulated LH release, indicate that activation of protein kinase C by endogenous diacylglycerols may serve as an amplifier of the GnRH-stimulated signal which appears to be mediated independently by the Ca2+-calmodulin system.

Animals↗
PubMed1984

Activation of luteinizing hormone release from pituitary cells by polycations.

In the present work we examined the effect of cationic polymers on the pituitary gonadotrope. Such polymers are widely used to anchor gonadotropes and other cell types to culture dishes and other substrata to which they are not normally adherent. Homopolymers of Lys (eight size classes from 4,000-700,000 daltons) stimulate Ca+2-dependent LH release from pituitary cell cultures. In contrast, release does not occur in response to the epsilon-CBZ or succinyl derivatives (which have no internal charge) or in response to polymers of L-Glu, D-Glu, or Gly. The observation that polymers of D-Lys, L-Lys, and L-Arg all stimulate LH release with similar efficacy and potency indicates that simple charge interactions, rather than interaction with specific polymer-binding sites, are the cause of LH release. Since monomeric Lys neither stimulates LH release nor competitively inhibits release in response to Lys polymers, it appears that multiple charge coordination by Lys polymers is responsible for activation of the release mechanism. Putrescine, spermine, and spermidine (which have more closely spaced charges) do not stimulate LH release, suggesting that a certain minimal distance of charge separation must occur to obtain efficacy. The reduced potency of heteropolymers of Lys (spaced with Ala or Tyr) suggests that a maximal effective distance also exists. Consecutive and concomitant incubation studies indicate that LH released in response to poly-L-Lys or GnRH comes from the same pool as that released by GnRH. The time courses of release are similar for the two compounds.

Animals↗
PubMed1982

Psychiatric day hospitalization: multiple perspectives on outcome.

Patients admitted over a three year period to a psychiatric day hospital were followed in order to: 1) substantiate the findings of other studies supportive of the short to intermediate term efficacy of psychiatric day hospitalization; 2) examine outcome on a number of dimensions and from a variety of perspectives; 3) examine issues relating to the differential efficacy of psychiatric day hospitalization; 4) discuss implications of the above factors in regards to planning effective day hospital programs.

Analysis of Variance↗
PubMed1976

Mutations masking the lambda cin-1 mutation.

A lambda cnc mutation masks the phenotype of the lambda cin-1 mutation. Eleven cnc mutations have been found. All appear to be identical and all map at a site just to the right of the cin-1 site. It is probable that cin-1 and cnc affect adjacent, or almost adjacent nucleotide pairs. Neither the cin-1 nor the cnc mutation involves large additions or deletions of genetic material.

Chromosome Mapping↗
PubMedDate not supplied

Tourette disorder: a cross-cultural review.

Tourette's disorder (TD) is a complex disorder of motor and vocal tics starting in childhood or adolescence. Although the disorder has been researched extensively in North America and Europe, clinical features and associated conditions of TD are less well known in other cultures. The English-language literature relating to TD was searched for cross-cultural case reports, clinical investigations, and epidemiological studies, and the subsequent database was analyzed. The clinical characteristics of TD displayed a strong similarity across cultures. Demography, family history, clinical features, associated conditions, comorbidity, and treatment outcome were essentially the same in the various cultures investigated. The disorder appears world-wide, has similar clinical characteristics, and most likely has an underlying biological and genetic basis.

Adolescent↗