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Biomedical subjects

S M Brooke

Publications and source records attributed to S M Brooke.

5 recordsLinked to original sources
PubMed1994

Characterization of mineralocorticoid and glucocorticoid receptors in primate brain.

Characteristics of neural corticosteroid receptors were studied in 51 adrenally-intact macaque monkeys using a modification of a corticosteroid receptor assay developed in this laboratory for rodent studies. Using cortisol as a ligand, two receptor subtypes could be distinguished and with similar Kd's to those observed in rodents, as measured with corticosterone. The time course showed maximum binding for mineralocorticoid receptors at 24 h and for glucocorticoid at 4 h. There were regional differences in the number of available binding sites for each receptor type, as well as an inverse correlation between the concentration of cortisol in the blood at the time of death and the number of available binding sites. In general this paper emphasizes the similarities between such receptors in primate and those in other species, similarities that could be detected despite the technical constraints of studying tissue taken from non-adrenalectomized animals.

Animals↗
PubMed1994

Dexamethasone resistance among nonhuman primates associated with a selective decrease of glucocorticoid receptors in the hippocampus and a history of social instability.

We have studied some of the neuroendocrine and social correlates of dexamethasone resistance in a nonhuman primate population. Subjects were 51 male Macaca fascicularis monkeys with known behavioral histories and who had been given dexamethasone (DEX) suppression tests a week prior to killing. We compared the subset of monkeys who were most DEX responsive (post-DEX cortisol values of 3.1 +/- 0.5 micrograms/dl) versus a DEX-resistant subset (cortisol values of 9.2 +/- 2.0 micrograms/dl); we found two features that distinguished these groups: (a) DEX-resistant monkeys had significantly fewer available glucocorticoid receptor (GR) binding sites in the hippocampus; they did not differ in numbers of mineralocorticoid receptor (MR) sites in the hippocampus, nor in numbers for either receptor in the cortex or hypothalamus as a whole. (b) Animals had resided for a number of years in social groups that were either stable or were repeatedly destabilized by changing of group membership; the latter has been shown to constitute a sustained stressor. DEX-resistant animals were more than twice as likely to have come from an unstable group as were DEX-responsive monkeys. Rodent studies have shown that sustained stress can cause a selective downregulatory decrease in the numbers of hippocampal corticosteroid receptors, and that such a loss is associated with DEX resistance. The present data suggest similar associations in the primate, and may be of relevance to the DEX resistance observed in a subset of human depressives.

Animals↗
PubMed1992

Possible mechanism by which stress accelerates growth of virally derived tumors.

Stress accelerates the growth of certain types of tumors. Here we report a possible metabolic mechanism underlying this phenomenon. Some early features of transformation include increased number of glucose transporters and greatly enhanced rates of glucose uptake; this adaptation accommodates the vast energy demands needed for neoplastic growth. In contrast, glucocorticoids, a class of steroid hormones secreted during stress, inhibit glucose transport in various tissues; this is one route by which circulating glucose concentrations are raised during stress. We reasoned that should transformed cells become resistant to this inhibitory action of glucocorticoids, such cells would gain preferential access to these elevated concentrations of glucose. In agreement with this, we observed that Fujinami sarcoma virus-transformed fibroblasts became resistant to this glucocorticoid action both in vitro and in the rat. As a result, under conditions where glucocorticoids exerted catabolic effects upon nontransformed fibroblasts (inhibition of metabolism and ATP concentrations), the opposite occurred in the virally transformed cells. We observe that this glucocorticoid resistance upon transformation cannot be explained by depletion of glucocorticoid receptors; previous studies have suggested that transformation causes an alteration in trafficking of such receptors. Because of this resistance of transformed fibroblasts to the inhibitory effects of glucocorticoids upon glucose transport, glucose stores throughout the body are, in effect, preferentially shunted to such tumors during stress.

Adenosine Triphosphate↗
PubMed1975

Effects of amphetamine isomers and neuroleptics on self-stimulation from the nucleus accumbens and dorsal noradrenergic bundle.

In an attempt to examine the possible role of noradrenergic (NA) and dopaminergic (DA) systems in intracranial self-stimulation (ICS), the rate-increasing effects of D- and L-amphetamine on ICS were determined in rats with nucleus accumbens electrodes (DA placement) or dorsal NA bundle electrodes (NA placement). The D-isomer produced a significantly greater increase in ICS than did the L-isomer in animals with dorsal NA bundle electrodes. In contrast, the amphetamine isomers were equipotent in facilitating ICS in animals with nucleus accumbens electrodes. These data, together with previous observations, suggest that there exists a correlation between equipotential effects of D- and L-amphetamine and DA electrode placements on the one hand, and prepotent effects of D-amphetamine and NA electrode placements on the other. Pimozide and haloperidol, which in low doses are thought to specifically block DA receptors, decreased ICS obtained from both DA and NA electrode placements. It is suggested that neuroleptic drugs may produce a general disruption of operant behavior and that the decrease in ICS produced by these agents does not therefore necessarily implicate dopaminergic mechanisms in the neurochemistry of reward.

Amphetamine↗