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1.
Gen Comp Endocrinol ; 177(1): 143-52, 2012 May 15.
Article in English | MEDLINE | ID: mdl-22433940

ABSTRACT

To examine the relative growth, endocrine, and gene expression effects of growth hormone (GH) transgenesis vs. GH protein treatment, wild-type non-transgenic and GH transgenic coho salmon were treated with a sustained-release formulation of recombinant bovine GH (bGH; Posilac). Fish size, specific growth rate (SGR), and condition factor (CF) were monitored for 14 weeks, after which endocrine parameters were measured. Transgenic fish had much higher growth, SGR and CF than non-transgenic fish, and bGH injection significantly increased weight and SGR in non-transgenic but not transgenic fish. Plasma salmon GH concentrations decreased with bGH treatment in non-transgenic but not in transgenic fish where levels were similar to controls. Higher GH mRNA levels were detected in transgenic muscle and liver but no differences were observed in GH receptor (GHR) mRNA levels. In non-transgenic pituitary, GH and GHR mRNA levels per mg pituitary decreased with bGH dose to levels seen in transgenic salmon. Plasma IGF-I was elevated with bGH dose only in non-transgenic fish, while transgenic fish maintained an elevated level of IGF-I with or without bGH treatment. A similar trend was seen for liver IGF-I mRNA levels. Thus, bGH treatment increased fish growth and influenced feedback on endocrine parameters in non-transgenic but not in transgenic fish. A lack of further growth stimulation of GH transgenic fish suggests that these fish are experiencing maximal growth stimulation via GH pathways.


Subject(s)
Growth Hormone/metabolism , Animals , Animals, Genetically Modified , Cattle , Growth Hormone/genetics , Growth Hormone/pharmacology , Insulin-Like Growth Factor I/genetics , Liver/drug effects , Liver/metabolism , Oncorhynchus kisutch , Pituitary Gland/drug effects , Pituitary Gland/metabolism
2.
Science ; 169(3946): 641-6, 1970 Aug 14.
Article in English | MEDLINE | ID: mdl-4988062

ABSTRACT

The impressive homologies between mitochondria and plastids, on the one hand, and procaryotic organisms, on the other, make it almost certain that these important cellular organelles had their origin as independent organisms. The vast number of symbiotic relationships of all degrees of evolutionary antiquity which have been found in contemporary organisms point to the ease with which such relationships can be established.


Subject(s)
Chloroplasts , Eukaryota/cytology , Mitochondria , Symbiosis , Biological Evolution , Carotenoids , Chlorophyta/cytology , Cyanobacteria/cytology , DNA/metabolism , Escherichia coli/cytology , Euglena/cytology , Neurospora/cytology , Photosynthesis
3.
Science ; 204(4390): 327, 1979 Apr 20.
Article in English | MEDLINE | ID: mdl-17800360

ABSTRACT

Although it has been postulated that genetic self-incompatibility was involved in the origin of complex heterozygotes in Oenothera subsect Euoenothera, it has not been detected in any species of this well-studied group. It is now reported for populations of Oenothera grandiflora from west central Alabama, and should be sought in other populations of this species, which has been in cultivation for nearly two centuries.

4.
Science ; 200(4343): 731-6, 1978 May 19.
Article in English | MEDLINE | ID: mdl-17743224

ABSTRACT

Existing geographical and ecological relationships between bats, non-flying mammals, and birds that visit flowers for food suggest novel interpretations of their evolutionary history.

5.
Science ; 154(3746): 273-5, 1966 Oct 14.
Article in English | MEDLINE | ID: mdl-17810308

ABSTRACT

A sample of 200 native plant names from the Tzeltal-speaking municipio of Tenejapa, Chiapas, Mexico, was found to consist of 41 percent that comprised more than one botanical species, 34 percent with a one-to-one correspondence, and 25 percent that referred to only a part of a botanical species. Cultural significance was least for the plants in the first group, greatest for those in the last group. Over half (60 percent) of the names for which there was one-to-one correspondence were plants associated with Hispanic culture, introduced as named entities following the Spanish conquest.

6.
Science ; 179(4076): 893-5, 1973 Mar 02.
Article in English | MEDLINE | ID: mdl-17832770

ABSTRACT

Regression analyses to determine plant species number are repeated for the GalƔpagos Islands with new data. The multiple curvilinear regression gives the best prediction of species number, with island area making the only significant contribution. The proportion of species endemic to the GalƔpagos is highest in the arid, transition zone and on small islands, and lowest in the littoral and mesic zones. This is explained in terms of zone-specific immigration and extinction rates and the very recent appearance of moist upland climates in the archipelago.

7.
Science ; 174(4015): 1210-3, 1971 Dec 17.
Article in English | MEDLINE | ID: mdl-17806924

ABSTRACT

There are approximately 10 million kinds of olganisms in the world, of which we have described some 15 percent. The rapid growth of the human population will cause most of the remainder to disappear from the earth before they are seen by a taxonomist. These facts suggest a more rigorous application of priorities in systematic biology as well as a careful review of the principles upon which our taxonomic system is based. Folk taxonomies all over the world are shallow hierarchically and comprise a strictly limited number of generic taxa ranging from about 250 to 800 forms applied to plants and a similar number applied to animals. These numbers are consistent, regardless of the richness of the environment in which the particular people live. Very few specific and varietal taxa are recognized in folk taxonomic systems. Until the invention of movable type in the mid-l5th century, written taxonomies were simply records of the folk taxonomies of particular regions. Subsequently, with the possibility for the wide distribution of books, it began to seem worth while to attempt to describe and name all species of plants and animals in the world. By the year 1700, 698 genera of plants were recognized; and by the year 1778, some 1350 genera, including tens of thousands of species. In 1789 de Jussieu interpolated the family as a higher level taxonomic category in an attempt to reduce the number of important units in the system to a memorable number. The family is still the focal point in systems of angiosperm classification at present, several hundred families being recognized. Problems with the taxonomic system stem largely from the fact that it is not designed as an information retrieval device. In folk taxonomies, names are given to organisms and these are used to communicate about the organisms with others who already know the culturally significant properties of the organisms being discussed. In dealing with the vast numbers of organisms that exist, we tend to overemphasize the process of classification and the decisions it involves at the expense of the information about the organisms that we are supposedly accumulating. Frequent changes in names exacerbate the difficulties of the system and render it still less useful for information retrieval. With modern electronic data processing equipment, it has become possible to record information about organisms, to retain this information in a data bank, and to utilize it for various purposes, including the construction of various taxonomic systems. The invention of high-speed electronic data processing equipment is seen as analogous to but more important than the invention of movable type in the history of systematic biology. By using such equipment to its full potentialities, we should be able to achieve a qualitative improvement in our perception of the living world.

8.
Science ; 222(4630): 1293-300, 1983 Dec 23.
Article in English | MEDLINE | ID: mdl-6658451

ABSTRACT

Subfreezing temperatures, low light levels, and high doses of ionizing and ultraviolet radiation extending for many months after a large-scale nuclear war could destroy the biological support systems of civilization, at least in the Northern Hemisphere. Productivity in natural and agricultural ecosystems could be severely restricted for a year or more. Postwar survivors would face starvation as well as freezing conditions in the dark and be exposed to near-lethal doses of radiation. If, as now seems possible, the Southern Hemisphere were affected also, global disruption of the biosphere could ensue. In any event, there would be severe consequences, even in the areas not affected directly, because of the interdependence of the world economy. In either case the extinction of a large fraction of the Earth's animals, plants, and microorganisms seems possible. The population size of Homo sapiens conceivably could be reduced to prehistoric levels or below, and extinction of the human species itself cannot be excluded.


Subject(s)
Environment , Nuclear Warfare , Animals , Atmosphere , Climate , Humans , Photosynthesis , Radiation, Ionizing , Radioactive Fallout , Sunlight , Temperature , Ultraviolet Rays
9.
Gen Comp Endocrinol ; 159(1): 26-37, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18713628

ABSTRACT

Non-transgenic (wild-type) coho salmon (Oncorhynchus kisutch), growth hormone (GH) transgenic salmon (with highly elevated growth rates), and GH transgenic salmon pair fed a non-transgenic ration level (and thus growing at the non-transgenic rate) were examined for plasma hormone concentrations, and liver, muscle, hypothalamus, telencephalon, and pituitary mRNA levels. GH transgenic salmon exhibited increased plasma GH levels, and enhanced liver, muscle and hypothalamic GH mRNA levels. Insulin-like growth factor-I (IGF-I) in plasma, and growth hormone receptor (GHR) and IGF-I mRNA levels in liver and muscle, were higher in fully fed transgenic than non-transgenic fish. GHR mRNA levels in transgenic fish were unaffected by ration-restriction, whereas plasma GH was increased and plasma IGF-I and liver IGF-I mRNA were decreased to wild-type levels. These data reveal that strong nutritional modulation of IGF-I production remains even in the presence of constitutive ectopic GH expression in these transgenic fish. Liver GHR membrane protein levels were not different from controls, whereas, in muscle, GHR levels were elevated approximately 5-fold in transgenic fish. Paracrine stimulation of IGF-I by ectopic GH production in non-pituitary tissues is suggested by increased basal cartilage sulphation observed in the transgenic salmon. Levels of mRNA for growth hormone-releasing hormone (GHRH) and cholecystokinin (CCK) did not differ between groups. Despite its role in appetite stimulation, neuropeptide Y (NPY) mRNA was not found to be elevated in transgenic groups.


Subject(s)
Animals, Genetically Modified/genetics , Growth Hormone/genetics , Oncorhynchus kisutch/genetics , Animals , Animals, Genetically Modified/blood , Animals, Genetically Modified/metabolism , Cholecystokinin/genetics , Growth Hormone/blood , Growth Hormone/metabolism , Growth Hormone-Releasing Hormone/genetics , Hypothalamus/metabolism , Insulin-Like Growth Factor I/genetics , Liver/metabolism , Muscles/metabolism , Neuropeptide Y/genetics , Oncorhynchus kisutch/blood , Oncorhynchus kisutch/metabolism , Pituitary Gland/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Somatotropin/genetics , Telencephalon/metabolism
11.
J Endocrinol ; 189(2): 211-8, 2006 May.
Article in English | MEDLINE | ID: mdl-16648289

ABSTRACT

The exploratory behaviour of the genetically derived Maudsley rat model of emotionality has been well characterized. Maudsley reactives (MR) present with more 'anxious-like' behaviour than Maudsley nonreactives (MNR). Although this behaviour is assumed to be associated with altered adrenocortical function, the few studies addressing this issue have produced inconsistent findings. We therefore set out to investigate the adrenal endocrinology of the MR and MNR strains. Control Wistars, the ancestors of the Maudsleys, have been used for the first time to set the baseline for all the experiments carried out. It was found that the MNR strain had a significantly blunted adrenocorticotrophic hormone (ACTH) response to restraint stress compared with Wistars, but a normal corticosterone response. Conversely, the MR had a significantly exaggerated ACTH response to restraint stress, but a normal corticosterone response. This finding suggested that the MR adrenal is less sensitive to ACTH than the MNR. This was confirmed by investigating the corticosterone dose-response to ACTH in adrenals from the two strains incubated in vitro. Several possible intra-adrenal regulators were investigated, but the only significant molecular difference in the adrenal glands from the two strains was the level of expression of neuropeptide Y (NPY), which is known to be a stress-responsive peptide in the adrenal. We propose that intra-adrenal NPY is responsible for blunting adrenocortical responses to ACTH stimulation in the MR strain. The observed changes in adrenal NPY suggest that this rat strain may serve as a model of chronic stress, with the MR phenotype representing maladaptation.


Subject(s)
Adrenal Glands/physiology , Behavior, Animal/physiology , Emotions/physiology , Stress, Psychological/physiopathology , Adrenocorticotropic Hormone/blood , Adrenocorticotropic Hormone/physiology , Aldosterone/blood , Aldosterone/physiology , Animals , Corticosterone/blood , Corticosterone/physiology , Gene Expression/genetics , Male , Models, Animal , Neuropeptide Y/analysis , Neuropeptide Y/genetics , Rats , Rats, Wistar , Restraint, Physical
12.
Best Pract Res Clin Endocrinol Metab ; 20(1): 111-20, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16522523

ABSTRACT

Considering the wide range of chemicals known to disrupt adrenal function and the physiological importance of the adrenal cortex, it is surprising that endocrine disruption of the adrenal gland has not been more widely researched. The chemical nature of adrenal disruptors is highly varied, and there are features of the adrenal structure and function, which render it particularly vulnerable to toxic attack. However, the homeostatic mechanisms inherent in the hypothalamo-pituitary-adrenal axis mean that only the most catastrophic effects are recognized as adrenal disruption, such as in the case of etomidate. In order to detect potentially significant but milder forms of toxic disruption of adrenal function a new approach is needed; this requires the use of more sophisticated approaches than simply measuring one hormone at one time point. New methodologies are also needed, such as the use of human adrenal cell lines for the screening of toxins and for mechanistic investigation of adrenal disruptors. This review focuses on mechanisms of adrenal toxicity and on the challenges facing researchers in this important field.


Subject(s)
Adrenal Glands/drug effects , Endocrine Disruptors/pharmacology , Adrenal Glands/physiology , Adrenocorticotropic Hormone/physiology , Animals , Etomidate/adverse effects , Humans , Mineralocorticoid Excess Syndrome, Apparent/physiopathology , Pituitary-Adrenal System/drug effects , Pituitary-Adrenal System/physiology , Steroid 11-beta-Hydroxylase/antagonists & inhibitors
13.
Environ Pollut ; 137(1): 83-101, 2005 Sep.
Article in English | MEDLINE | ID: mdl-15944042

ABSTRACT

We report biological changes at several UK Acid Waters Monitoring Network lakes and streams that are spatially consistent with the recovery of water chemistry induced by reductions in acid deposition. These include trends toward more acid-sensitive epilithic diatom and macroinvertebrate assemblages, an increasing proportional abundance of macroinvertebrate predators, an increasing occurrence of acid-sensitive aquatic macrophyte species, and the recent appearance of juvenile (<1 year old) brown trout in some of the more acidic flowing waters. Changes are often shown to be directly linked to annual variations in acidity. Although indicative of biological improvement in response to improving water chemistry, "recovery" in most cases is modest and very gradual. While specific ecological recovery endpoints are uncertain, it is likely that physical and biotic interactions are influencing the rate of recovery of certain groups of organisms at particular sites.


Subject(s)
Acid Rain , Ecosystem , Water Pollutants, Chemical/analysis , Animals , Conservation of Natural Resources , Crustacea , Diatoms , Environmental Monitoring/methods , Eukaryota , Fishes , Fresh Water , Invertebrates , Population Dynamics , Time Factors , United Kingdom , Zooplankton
14.
Am J Psychiatry ; 158(1): 134-6, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11136648

ABSTRACT

OBJECTIVE: Anxiety states induced experimentally or occurring naturally potentiate the startle reflex elicited by sudden sensory stimuli in both animals and human beings. The authors investigated whether patients with obsessive-compulsive disorder (OCD) show exaggerated startle reactions to acoustic probes, especially during negative-affect-toned stimuli, compared with healthy subjects. METHOD: Ten patients with OCD and 10 age- and sex-matched comparison subjects were shown a series of film clips. Two of the film clips had positive valence, two had negative valence, and two had relatively neutral valence. The subjects' eyeblink startle response was measured in reaction to startle-eliciting stimuli presented three times binaurally during each film clip. RESULTS: Patients with OCD produced larger startle reflexes and shorter latencies to onset of startle response than the comparison subjects over the entire session. CONCLUSIONS: Patients with OCD were excessively responsive to startle-eliciting stimuli. This effect may be associated with the development or maintenance of OCD.


Subject(s)
Acoustic Stimulation , Obsessive-Compulsive Disorder/diagnosis , Reflex, Startle/physiology , Adult , Affect/physiology , Female , Hospitalization , Humans , Male , Motion Pictures , Obsessive-Compulsive Disorder/psychology , Reaction Time/physiology , Visual Perception/physiology
15.
Neuroscience ; 95(2): 535-41, 2000.
Article in English | MEDLINE | ID: mdl-10658634

ABSTRACT

The aim of the present study was to investigate changes in contralateral nerves associated with peripheral nerve injuries. Transection and subsequent regeneration of the saphenous nerve on one side caused a suppression of the ability of the contralateral saphenous nerve to produce a neurogenic plasma extravasation response. This effect was transient, and was first evident two weeks after injury, reaching its maximum at four weeks, but was no longer detectable at eight weeks. This change was paralleled by a decrease in the content of substance P, a neuropeptide involved in neurogenic plasma extravasation, in the contralateral nerve. The neurotoxin capsaicin was used to deplete the nerve of a subclass of C-fibres, namely the polymodal nociceptor afferents. Pretreatment of the nerve to be lesioned with capsaicin was sufficient to significantly attenuate the changes in the plasma extravasation response and substance P content observed on the contralateral side. The effectiveness of the capsaicin treatment was confirmed by histological examination. These results strongly suggest that changes observed at a site distant from the location of the nerve injury are dependent on the integrity of capsaicin-sensitive C-fibre afferents within the injured nerve. Furthermore, given that the contralateral nerve has commonly been used as the control for an injury conducted on the homologous nerve or muscle on the opposite side of the body, the underlying assumption being that the contralateral nerve remained unchanged, the present findings emphasize the need for separate groups of control animals which have undergone no surgical procedures.


Subject(s)
Capsaicin/pharmacology , Neurons, Afferent/physiology , Peripheral Nerves/physiopathology , Signal Transduction/drug effects , Animals , Capillary Permeability , Coloring Agents/pharmacokinetics , Denervation , Functional Laterality , Male , Neuritis/pathology , Neuritis/physiopathology , Neurons, Afferent/chemistry , Neurons, Afferent/immunology , Nociceptors/physiology , Peripheral Nerve Injuries , Peripheral Nerves/cytology , Plasma/metabolism , Radioimmunoassay , Rats , Rats, Wistar , Skin/innervation , Substance P/analysis
16.
Am J Cardiol ; 56(15): 932-7, 1985 Dec 01.
Article in English | MEDLINE | ID: mdl-4072926

ABSTRACT

The effects of increasing and decreasing cardiac preload by 15% on the left ventricular (LV) performance of 11 carefully screened normal subjects aged 61 to 73 years were examined. Comparisons were made with 11 subjects aged 21 to 28 years. Two-dimensional echocardiograms were obtained before and at the termination of 5 degrees of head-down tilt for 90 minutes and at the termination of graded lower body negative pressure to -40 mm Hg. Heart rates and blood pressures were unchanged after physiologic interventions. Changes in LV end-diastolic and stroke volumes were similar but of a smaller magnitude in the older subjects compared with changes in younger subjects. When LV end-diastolic volumes obtained at each extreme of preload variation were compared, the range of mean change was less in the older (23 ml, 26%) than in the younger subjects (31 ml, 41%). Control LV end-diastolic and end-systolic volumes were greater in the older subjects. This study shows that despite larger control LV volumes, alterations in preload produce changes in the LV end-diastolic and stroke volumes of these older subjects that conform to the normal LV function curve, but that these responses are diminished compared with changes in younger subjects, suggesting an age-related change in diastolic stiffness.


Subject(s)
Heart/physiology , Age Factors , Aged , Blood Pressure , Blood Volume , Echocardiography , Humans , Middle Aged
17.
J Endocrinol ; 163(1): 1-5, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10495400

ABSTRACT

Dehydroepiandrosterone (DHEA) is a steroid secreted by the adrenal cortex, with a characteristic, age-related, pattern of secretion. The decline of DHEA concentrations with age has led to the suggestion that old age represents a DHEA deficiency syndrome and that the effects of ageing can be counteracted by DHEA 'replacement therapy'. DHEA is increasingly being used in the USA, outside medical supervision, for its supposed anti-ageing effects. This commentary weighs the evidence for the existence of a DHEA deficiency syndrome and considers the value of DHEA 'replacement therapy'.


Subject(s)
Aging/physiology , Dehydroepiandrosterone/deficiency , Hormone Replacement Therapy , Adolescent , Adrenal Cortex/metabolism , Adult , Aged , Aged, 80 and over , Child , Cognition Disorders/blood , Dehydroepiandrosterone/blood , Dehydroepiandrosterone/therapeutic use , Dehydroepiandrosterone Sulfate/blood , Female , Humans , Hydrocortisone/blood , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/drug therapy , Male , Middle Aged
18.
J Endocrinol ; 99(1): 13-22, 1983 Oct.
Article in English | MEDLINE | ID: mdl-6313838

ABSTRACT

The finding that incubation of rat adrenal capsules (largely zona glomerulosa) with trypsin reproducibly releases aldosterone and 18-hydroxycorticosterone (18-OH-B) from tightly protein-bound tissue stores leads to the hypothesis that the secretion of these steroids may be under the control of endogenous proteases. Rat adrenal capsule whole tissue and collagenase-dispersed cells were incubated under conditions of stimulation by (1-24)ACTH (10(-7) mol/l), potassium (8.4 X 10(-3) mol/l) or dibutyryl cyclic AMP (dbcAMP) (10(-4) mol/l) with the addition in some flasks of one of the following protease inhibitors at the appropriate concentration for their known actions: N alpha-p-tosyl-L-arginine methyl ester (TAME; 10(-2) mol/l), 2-nitro-4-carboxyphenyl-N,N'-diphenylcarbamate (NCDC; 2 X 10(-6) mol/l), N alpha-benzoyl-L-arginine (BA; 10(-2) mol/l), p-nitrophenyl-N alpha-benzyloxycarbonyl-L-lysinate (CBZ-NL; 2 X 10(-6) mol/l) and soybean trypsin inhibitor (STI; 1 mg/ml). The (1-24)ACTH-stimulated steroid output in dispersed cells was not affected by NCDC, BA or CBZ-NL. However, all of the inhibitors except STI produced selective effects on aldosterone and 18-OH-B production by whole capsule tissue under certain conditions. Thus TAME and NCDC significantly inhibited the dbcAMP-stimulated production of these two steroids (aldosterone values decreased from 328 +/- 35 to 128 +/- 15 and 157 +/- 32 ng/gland pair respectively) and furthermore NCDC elicited the same effect in potassium- or ACTH-stimulated whole tissue (e.g. in K+-stimulated tissue aldosterone decreased from 79 +/- 15 to 40 +/- 7 ng/gland pair). The reverse effect was shown by BA and CBZ-NL in potassium-stimulated whole tissue, and yields of aldosterone and 18-OH-B were significantly enhanced (aldosterone increased from 79 +/- 15 ng/pair to 151 +/- 14 ng in the presence of BA). The high molecular weight inhibitor STI had no effect on potassium-stimulated whole tissue, but enhanced the yield of extractable aldosterone from 9.7 +/- 1.7 to 16.9 +/- 2.3 ng/pair when added to incubations of a cytosol preparation. The results suggest that endogenous proteases in rat adrenal whole capsule tissue play specific roles in the control of aldosterone and 18-OH-B secretion. Some (type 1) whose action is mimicked by trypsin, are inhibited by TAME and NCDC and appear to be involved in the release of these two steroids from their tight (apparently covalent) binding to protein.(ABSTRACT TRUNCATED AT 400 WORDS)


Subject(s)
18-Hydroxycorticosterone/metabolism , Adrenal Glands/metabolism , Aldosterone/metabolism , Corticosterone/analogs & derivatives , Protease Inhibitors/pharmacology , Adrenal Glands/drug effects , Animals , Bucladesine/pharmacology , Cells, Cultured , Cosyntropin/pharmacology , Culture Techniques , Female , Potassium/pharmacology , Rats , Stimulation, Chemical
19.
J Endocrinol ; 169(3): 581-5, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11375128

ABSTRACT

Stimulation of aldosterone by a serine protease, trypsin, was first reported in 1982, although the mechanism of this effect was unclear. Recently, a family of protease-activated receptors (PARs) has been described and four members of the family characterised and cloned, including the previously recognised thrombin receptor. This study investigated whether PARs mediate the action of trypsin on aldosterone secretion. Using intact rat adrenal capsular tissue, thrombin was found to increase aldosterone secretion, and the effects of trypsin on aldosterone secretion were confirmed. Both trypsin and thrombin were shown to activate phospholipase C, as measured by an increase in inositol triphosphate turnover by adrenal capsular tissue. It was also shown that U73122, a phospholipase C inhibitor, attenuated the aldosterone response to trypsin. These effects were consistent with the activation of a PAR. Northern blot analysis revealed the presence of mRNA encoding PAR-1, but not PARs-2, -3 or -4 in the adrenal capsule/zona glomerulosa. Messenger RNA encoding PAR-1 was increased by dietary sodium depletion, consistent with previous reports of an increased response to trypsin after sodium depletion. These data suggest that the actions of trypsin on aldosterone secretion are mediated by PAR-1.


Subject(s)
Adrenal Cortex/metabolism , Aldosterone/metabolism , Receptors, Thrombin/physiology , Adrenal Cortex/drug effects , Angiotensin II/pharmacology , Animals , Blotting, Northern , Culture Techniques , Dose-Response Relationship, Drug , Female , Inositol Phosphates/biosynthesis , Male , RNA, Messenger/genetics , Rats , Rats, Wistar , Receptor, PAR-1 , Receptors, Thrombin/genetics , Sodium, Dietary/administration & dosage , Thrombin/pharmacology , Trypsin/pharmacology , Type C Phospholipases/metabolism
20.
Psychoneuroendocrinology ; 21(3): 277-86, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8817726

ABSTRACT

In order to investigate mechanisms by which the adrenal 11 beta-hydroxylase inhibitor metyrapone might exert its antidepressant effect, we used gas chromatography to analyse the 24 h urinary steroid profiles from six females with major depression taking part in a trial of metyrapone (2-4 g/day) as an antidepressant. Due to concurrent administration of hydrocortisone (30 mg/day), plasma cortisol levels were not significantly reduced. Treatment with metyrapone resulted in greatly increased urinary excretion of 11-deoxy corticosteroids, including the GABA-modulatory steroid tetrahydro-11-deoxycorticosterone (from 68 +/- 34 to 219 +/- 75 micrograms/24 h, p < .05). Metyrapone also had multiple extra-adrenal effects on corticosteroid metabolism, including inhibition of the peripheral conversion of cortisone to cortisol as demonstrated by a significant decrease in the ratio of 11 beta-hydroxy/11-oxo metabolites of cortisol (from 0.81 +/- 0.08 to 0.46 +/- 0.04, p < .01). The decreased Montgomery-Asberg Depression Rating Scale scores seen during treatment with metyrapone did not correlate with changes in plasma cortisol, but did correlate significantly with total 11-deoxycortisol metabolites (r = 0.778, n = 12, p < .01). We conclude that, in addition to decreased cortisol synthesis, increased secretion of cortisol precursors and reduced local bioavailability of cortisol may play a role in the antidepressant effect of metyrapone.


Subject(s)
Affect/drug effects , Affect/physiology , Antidepressive Agents/therapeutic use , Depressive Disorder/drug therapy , Metyrapone/therapeutic use , Steroids/urine , Adult , Depressive Disorder/psychology , Depressive Disorder/urine , Female , Humans , Hydrocortisone/blood , Hydrocortisone/urine , Middle Aged , Psychiatric Status Rating Scales
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