Combined pituitary hormone deficiency: current and future status.

Over the last two decades, the understanding of the mechanisms involved in pituitary ontogenesis has largely increased. Since the first description of POU1F1 human mutations responsible for a well-defined phenotype without extra-pituitary malformation, several other genetic defects of transcription factors have been reported with variable degrees of phenotype-genotype correlations. However, to date, despite the identification of an increased number of genetic causes of isolated or multiple pituitary deficiencies, the etiology of most (80-90 %) congenital cases of hypopituitarism remains unsolved. Identifying new etiologies is of importance as a post-natal diagnosis to better diagnose and treat the patients (delayed pituitary deficiencies, differential diagnosis of a pituitary mass on MRI, etc.), and as a prenatal diagnosis to decrease the risk of early death (undiagnosed corticotroph deficiency for instance). The aim of this review is to summarize the main etiologies and phenotypes of combined pituitary hormone deficiencies, associated or not with extra-pituitary anomalies, and to suggest how the identification of such etiologies could be improved in the near future.

Decreased glucose tolerance and plasma adiponectin:resistin ratio in a mouse model of post-traumatic stress disorder.

AIMS/HYPOTHESIS: Obesity and type 2 diabetes are among the most serious health pathologies worldwide. Stress has been proposed as a factor contributing to the development of these health risk factors; however, the underlying mechanisms that link stress to obesity and diabetes need to be further clarified. Here, we study in mice how chronic stress affects dietary consumption and how that relationship contributes to obesity and diabetes. METHODS: C57BL/6J mice were subjected to chronic variable stress (CVS) for 15 days and subsequently fed with a standard chow or high-fat diet. Food intake, body weight, respiratory quotient, energy expenditure and spontaneous physical activity were measured with a customised calorimetric system and body composition was measured with nuclear magnetic resonance. A glucose tolerance test was also applied and blood glucose levels were measured with a glucometer. Plasma levels of adiponectin and resistin were measured using Lincoplex kits. RESULTS: Mice under CVS and fed with a high-fat diet showed impaired glucose tolerance associated with low plasma adiponectin:resistin ratios. CONCLUSIONS/INTERPRETATION: This study demonstrates, in a novel mouse model, how post-traumatic stress disorder enhances vulnerability for impaired glucose metabolism in an energy-rich environment and proposes a potential adipokine-based mechanism.

Regulatory interactions of stress and reward on rat forebrain opioidergic and GABAergic circuitry.

Palatable food intake reduces stress responses, suggesting that individuals may consume such ?comfort? food as self-medication for stress relief. The mechanism by which palatable foods provide stress relief is not known, but likely lies at the intersection of forebrain reward and stress regulatory circuits. Forebrain opioidergic and gamma-aminobutyric acid ergic signaling is critical for both reward and stress regulation, suggesting that these systems are prime candidates for mediating stress relief by palatable foods. Thus, the present study (1) determines how palatable ?comfort? food alters stress-induced changes in the mRNA expression of inhibitory neurotransmitters in reward and stress neurocircuitry and (2) identifies candidate brain regions that may underlie comfort food-mediated stress reduction. We used a model of palatable ?snacking? in combination with a model of chronic variable stress followed by in situ hybridization to determine forebrain levels of pro-opioid and glutamic acid decarboxylase (GAD) mRNA. The data identify regions within the extended amygdala, striatum, and hypothalamus as potential regions for mediating hypothalamic-pituitary-adrenal axis buffering following palatable snacking. Specifically, palatable snacking alone decreased pro-enkephalin-A (ENK) mRNA expression in the anterior bed nucleus of the stria terminalis (BST) and the nucleus accumbens, and decreased GAD65 mRNA in the posterior BST. Chronic stress alone increased ENK mRNA in the hypothalamus, nucleus accumbens, amygdala, and hippocampus; increased dynorphin mRNA in the nucleus accumbens; increased GAD65 mRNA in the anterior hypothalamus and BST; and decreased GAD65 mRNA in the dorsal hypothalamus. Importantly, palatable food intake prevented stress-induced gene expression changes in subregions of the hypothalamus, BST, and nucleus accumbens. Overall, these data suggest that complex interactions exist between brain reward and stress pathways and that palatable snacking can mitigate many of the neurochemical alterations induced by chronic stress.

Pinning of adsorbed cobalt atoms by defects embedded in the copper (111) surface.

Using a low-temperature scanning tunneling microscope (STM), we observe that Co adatoms are unusually strongly bound to a particular type of pinning centers on the Cu(111) surface. Using density-functional-theory calculations, the pinning centers are identified as Ag substitutional atoms embedded in the topmost atomic layer of the surface. These impurities are hardly detectable in the STM images as they have low topographic height and produce no standing-wave patterns. They do not affect the exchange coupling of the Co adsorbate with the substrate electrons; thus, the Kondo resonances measured on pinned and free Co adatoms show no detectable differences. Whereas free Co adatoms undergo significant surface diffusion already above 8 K, Ag-stabilized Co adatoms remain pinned up to 12.7 K.

Chronic stress produces enduring decreases in novel stress-evoked c-fos mRNA expression in discrete brain regions of the rat.

Chronic stress produces numerous adaptations within the hypothalamic-pituitary-adrenal (HPA) axis that persist well after cessation of chronic stress. We previously demonstrated profound attenuation of HPA axis responses to novel environment 4-7 days following chronic stress. The present study tests the hypothesis that this HPA axis hyporesponsivity is associated with reductions in stress-evoked c-fos mRNA expression, a marker of neuronal activation, in discrete brain regions. Adult male Sprague-Dawley rats underwent 1 week of chronic variable stress (CVS), with unhandled rats serving as controls. Independent groups of control and CVS rats were exposed to novel environment at 16 h, 4 days, 7 days, or 30 days after CVS. Marked reductions of c-fos mRNA expression in the CVS group persisted for at least 30 days within the paraventricular nucleus of the hypothalamus, and for at least 1 week in rostroventrolateral septum and lateral hypothalamus. Lower levels of c-fos mRNA expression were observed at 16 h recovery in the ventrolateral medial preoptic area, basolateral amygdala, anterior cingulate cortex, and prelimbic cortex. The results demonstrate long-term alterations in neuronal activation within neurocircuits critical for regulation of physiological and psychological responses to stressors.

Upgrading system-oriented ecotoxicological research.

In the 1990s the Dutch government expressed the need to investigate the impacts of diffuse pollution at (sub)-ecosystem levels. The resulting Netherlands Stimulation Programme on System-oriented Ecotoxicological Research (SSEO programme) ran from 1998 to 2006. Its primary objective was to assess the impacts of low- to medium-level, diffuse, multiple contaminations on ecosystems. The research results were intended as underpinning for policies on environmental, conservation and nature issues. Research was carried out at three sites that were selected because of their importance for nature management and the presence of diffuse contamination. These sites were: a river meadow/floodplain area (Afferdensche en Deestsche Waarden), an estuarine reed-land area (Biesbosch) and an area of lowland peat soils that had been contaminated with urban waste in past centuries (De Ronde Venen). This introductory paper describes the set-up of the programme, the types of diffuse contamination, the interactions between pollutants and other stress factors, the various methodologies used to integrate the effects on (sub)ecosystem level, and the consequences for formulating policies for and the management of these types of locations. The results of the programme are diverse and complicated and show how difficult it is to draw firm, unambiguous, generic conclusions about the effects at the 'total' ecosystem level. It is however, possible to draw conclusions about effects on major components of ecosystems: 1) The distribution of contaminants, both from a spatial, chemical and ecotoxicological point of view, plays a decisive role in actual effect levels. Even when total contaminant loads are high, such as in estuarine and floodplain areas, bioavailability may be so low that the actual effects are limited. The irregular, heterogeneous, spatial distribution of contaminants in the soil further complicates effect studies, impact assessments and monitoring. 2) Various stress factors, other than contaminants, both natural and anthropogenic, also play a role. The negative effect of the repeated inundation of floodplain areas, for instance, greatly interferes with the impact of contaminants in the lower soil layers. 3) A major problem is to find a method to extrapolate the observations from individual and population levels to the ecosystem level. In addition to traditional food-chain models and similar approaches, the potential of other, not yet extensively explored, ecosystem interaction mechanisms is discussed. 4) Finally, the results have to be interpreted from a policy point of view, both for national soil policies and for implementing the EU Soil Strategy regulations.

System-oriented ecotoxicological research: which way to go?

This paper presents an overview of the possibilities for further development of tools and. approaches for the ecological assessment and management of diffusively contaminated ecosystems. It is based on the results of the "Netherlands Stimulation Programme on Ecosystem-oriented Ecotoxicological Research", the SSEO programme, which ran from 1998 to 2006, and on opinions of international experts on ecological and ecotoxicological risk-assessment methods and their legal applications. The paper also discusses the pros and cons of the set-up of the SSEO programme. Proper management of diffusively polluted areas has to be based on an integral risk-based and system approach. The approach has to be founded on the relationships between pollution, natural stresses, management measures and the presence and activities of specific species. Furthermore, the relationships between biodiversity in ecosystems and its stability and functioning have to be known. The assessment of aquatic ecosystem quality is now based on the comparisons of the composition of actual species with that of reference species. This type of system does not yet exist for the assessment of soil quality, but it is being developed. It is shown that ecological quality criteria based on a Species Sensitivity Distributions approach are sufficiently conservative to avoid or prevent major ecological impacts of diffuse pollution at concentrations below legal standards. However, a proper quality relationship of biodiversity and ecosystem functioning is lacking in the ecological assessment methods. Future research should focus on the relationship of ecosystem structure (species composition) and ecosystem functioning and on the impact of disturbing the environment and appropriate management measures.

Ecological effects of diffuse mixed pollution are site-specific and require higher-tier risk assessment to improve site management decisions: a discussion paper.

Many Dutch ecosystems, whether terrestrial, aquatic or sediment-based, are diffusely polluted by mixtures of contaminants, whose concentrations often exceed regulatory Safe Values or other generic quality criteria. This situation has unclear consequences, especially when local authorities are confronted with such pollution. Water managers are frequently in doubt whether their water systems satisfy the criteria for 'Good Ecological Status' as defined in the EU's Water Framework Directive. In case of soils, soil users may wonder whether the soil is 'fit for use'. In case of nature conservation, the problem is that protected species might suffer from toxic stress. Official regulations in these cases call for appropriate action, but it is unclear whether the diffuse exposure causes adverse effects, and what the action should be. This paper proposes and discusses a site-oriented approach in the risk assessment of diffusely contaminated sites that can be used in addition to the compound-oriented policies from which the abovementioned generic quality criteria were derived. The site-oriented approach can be of help in reducing site-specific risks of diffuse contamination. Reflecting on the results of a large Dutch research effort in systems-oriented ecotoxicological effects, the conclusion is drawn that exposure and effects of diffuse pollution are site-specific in kind and magnitude, determined by the local combination of source-pathway-receptor issues, and often not clearly detectable (though often present). To assist in risk management, higher-tier methods can address various aspects, like addressing local mixture composition, bioavailability, and sensitivity of local species groups. Higher-tier risk assessment methods have as yet been developed mainly for cases of serious contamination, like for pesticide management and Risk-Based Land Management. For diffuse pollution, site-specific information can also be used to obtain site-specific exposure and impact information, while practical and ecology-based approaches can be introduced to obtain an integrated overview of the meaning of site contamination and to derive options for managing and reducing the local risks. These issues are discussed against the background of current major policy shifts, in The Netherlands and elsewhere, from a pollutant-oriented assessment to an additional ecological and site-oriented assessment. The latter is most clearly represented in the Good Ecological Status aim of the EU-Water Framework Directive. The paper assesses, integrates and discusses the results of the Dutch research effort in this policy context.

Metal redistribution by surface casting of four earthworm species in sandy and loamy clay soils.

Bioturbation of metal contaminated soils contributes considerably to redistribution and surfacing of contaminated soil from deeper layers. To experimentally measure the contribution of Allolobophora chlorotica, Aporrectodea caliginosa, Lumbricus rubellus and L. terrestris to soil surface casting, a time-course experiment was performed under laboratory conditions. Earthworms were incubated in perspex columns filled with sandy soil (2% organic matter, 2.9% clay) or loamy clay soil (15% organic matter, 20% clay), and surface casts were collected after up to 80 days. On the sandy soil, A. caliginosa and L. rubellus brought approximately 7.1-16 g dry wt. casts/g fresh wt. earthworm to the surface, which is significantly more than A. chlorotica and L. terrestris (2.5-5.0 g dry wt./g fresh wt.). A. caliginosa was the only species that produced significantly more surface casts in the sandy soil than in the loamy clay soil. In the loamy clay soil, no differences in biomass-corrected casting rates were found among the species. Surface casting rates tended to decrease after 20 days. Considering the densities of the different species in a Dutch floodplain area Afferdensche and Deestsche Waarden, surface cast production is estimated to amount to 2.0 kg dry soil/m2 after 80 days, which could be extrapolated to 2.7-9.1 kg/m2 per year. These amounts correspond to a surface deposition of a layer of approximately 1.9-6.5 mm/year, which is of the same order or even slightly higher than the sedimentation rate and much higher than the amount of soil brought to the soil surface by bioturbating small mammals.

Toxicological risks for small mammals in a diffusely and moderately polluted floodplain.

The ecotoxicological risk of heavy metal pollution in diffusely polluted floodplains is largely unclear, as field-based data are scarce. This study investigated cadmium (Cd) and lead (Pb) accumulation in the liver and kidneys of small mammal species (voles, mice and shrews) from a moderately polluted Dutch floodplain. The Cd and Pb concentrations were compared with effect concentrations (ECs). Reported ECs in literature varied considerably, with the lowest values frequently exceeded by our values, whereas the highest values were encountered only occasionally. Cd and Pb levels were highest in the shrew species, particularly in Sorex araneus. Although toxicological effects at the specimen level were present in these floodplains, effects at population level are thought to be limited, as a result of the animals' relatively short life expectancies (due to recurrent floods) and the rapid maturation of small mammals. Exceptionally high tissue metal concentrations in some specimens of all species indicated local hotspots with peaks in metal concentrations. Sanitizing such local hotspots might reduce toxicological risks.

The Equivalence Between Unit-Cell Twinning and Tiling in Icosahedral Quasicrystals.

It is shown that tiling in icosahedral quasicrystals can also be properly described by cyclic twinning at the unit cell level. The twinning operation is applied on the primitive prolate golden rhombohedra, which can be considered a result of a distorted face-centered cubic parent structure. The shape of the rhombohedra is determined by an exact space filling, resembling the forbidden five-fold rotational symmetry. Stacking of clusters, formed around multiply twinned rhombic hexecontahedra, keeps the rhombohedra of adjacent clusters in discrete relationships. Thus periodicities, interrelated as members of a Fibonacci series, are formed. The intergrown twins form no obvious twin boundaries and fill the space in combination with the oblate golden rhombohedra, formed between clusters in contact. Simulated diffraction patterns of the multiply twinned rhombohedra and the Fourier transform of an extended model structure are in full accord with the experimental diffraction patterns and can be indexed by means of three-dimensional crystallography. The alternative approach is fully compatible to the rather complicated descriptions in a hyper-space.

Chronic stress and Rosiglitazone increase indices of vascular stiffness in male rats.

Prolonged and/or frequent exposure to psychological stress responses may lead to deterioration of organs and tissues, predisposing to disease. In agreement with this, chronic psychosocial stress is linked to greater cardiovascular risk, including increased incidence of atherosclerosis, myocardial ischemia, coronary heart disease, and death. Thus the association between stress and cardiovascular dysfunction represents an important node for therapeutic intervention in cardiovascular disease. Here we report that 2weeks of chronic variable stress (CVS) increased indices of vascular stiffness, including increased collagen deposition in the aortic adventitia and increased resting pulse pressure, in male rats. Thus CVS may represent a useful rodent model for stress-associated CVD, especially for aging populations for which widening pulse pressure is a well-known risk factor. Additionally, we report that the thiazolidinedione Rosiglitazone (RSG) blunts chronic stress-associated increases in circulating corticosterone. Despite this, RSG was not protective against adverse cardiovascular outcomes associated with chronic stress. Rather RSG itself is associated with increased pulse pressure, and this is exacerbated by chronic stress-highlighting that chronic stress may represent an additional contributor to RSG-associated cardiovascular risk.

Neurocircuitry of stress: central control of the hypothalamo-pituitary-adrenocortical axis.

Integration of the hypothalamo-pituitary-adrenal stress response occurs by way of interactions between stress-sensitive brain circuitry and neuroendocrine neurons of the hypothalamic paraventricular nucleus (PVN). Stressors involving an immediate physiologic threat ('systemic' stressors) are relayed directly to the PVN, probably via brainstem catecholaminergic projections. By contrast, stressors requiring interpretation by higher brain structures ('processive' stressors) appear to be channeled through limbic forebrain circuits. Forebrain limbic sites connect with the PVN via interactions with GABA-containing neurons in the bed nucleus of the stria terminalis, preoptic area and hypothalamus. Thus, final elaboration of processive stress responses is likely to involve modulation of PVN GABAergic tone. The functional and neuroanatomical data obtained suggest that disease processes involving inappropriate stress control involve dysfunction of processive stress pathways.

Habituation to repeated restraint stress is associated with lack of stress-induced c-fos expression in primary sensory processing areas of the rat brain.

Rats repeatedly exposed to restraint show a reduced hypothalamic-pituitary-adrenal axis response upon restraint re-exposure. This hypothalamic-pituitary-adrenal axis response habituation to restraint does not generalize to other novel stressors and is associated with a decrease in stress-induced c-fos expression in a number of stress-reactive brain regions. We examined whether habituation to repeated restraint is also associated with adaptation of immediate early gene expression in brain regions that process and relay primary sensory information. These brain regions may not be expected to show gene expression adaptation to repeated restraint because of their necessary role in experience discrimination. Rats were divided into a repeated restraint group (five 1-hour daily restraint sessions) and an unstressed group (restraint naïve). On the sixth day rats from each group were either killed with no additional stress experience or at 15, 30 or 60 min during restraint. Immediate early gene expression (corticotrophin-releasing hormone heteronuclear RNA, c-fos mRNA, zif268 mRNA) was determined by in situ hybridization. A reduction in stress-induced hypothalamic-pituitary-adrenal axis hormone secretion (plasma corticosterone and adrenocorticotropic hormone) and immediate early gene expression levels in the paraventricular nucleus of the hypothalamus, the lateral septum and the orbital cortex was observed in repeated restraint as compared with restraint naïve animals. This reduction was already evident at 15 min of restraint. Unexpectedly, we also found in repeated restraint rats a reduction in restraint-induced c-fos expression in primary sensory-processing brain areas (primary somatosensory cortex, and ventroposteriomedial and dorsolateral geniculate nuclei of thalamus). The overall levels of hippocampal mineralocorticoid receptor heteronuclear RNA or glucocorticoid receptor mRNA were not decreased by repeated restraint, as may occur in response to severe chronic stress. We propose that repeated restraint leads to a systems-level adaptation whereby re-exposure to restraint elicits a rapid inhibitory modulation of primary sensory processing (i.e. sensory gating), thereby producing a widespread attenuation of the neural response to restraint.

Aging associated changes in amygdalar corticotropin-releasing hormone (CRH) and CRH-binding protein in Fischer 344 rats.

Behavioral adaptation in aging may become impaired from abnormal expression of amygdalar corticotropin-releasing hormone (CRH) and/or CRH-binding protein (CRH-BP). In this study, we serially sectioned the amygdala in 4-, 12-, and 24-month-old Fischer 344 rats following perfusion with 4% paraformaldehyde. We determined the amount of CRH and CRH-BP containing cells as well as the density of fibers expressing CRH or CRH-BP utilizing densitometric methods. Images were digitized using Zeiss Axiovision software and densitometrically analyzed using Scion Image. Both sides were analyzed in sections cut at 30 mum thickness. Cell counts of CRH-BP containing cells in the basolateral and lateral nucleus of the amygdala were lower in 24-month-old rats vs. 4-month-old rats, respectively (mean cells/section +/- SE): 31 +/- 6 vs. 72 +/- 10 (n = 3; P < 0.05 via ANOVA and Fisher's PLSD). There was a trend for cell counts of CRH containing cells in the central nucleus of the amygdala to be lower in 24-month-old rats vs. 4-month-old rats, respectively 28 +/- 7 vs. 47 +/- 9 (n = 3; P = 0.07 via ANOVA). Densitometric analysis of the number of CRH-BP positive fibers revealed no age differences in CeA; however, with regards to CRH-positive fibers, both 4- and 12-month rats had greater CeA CRH immunoreactivity relative to 24-month-old rats (Ps < 0.05 via ANOVA and Fisher's PLSD). These changes may contribute to impaired adaptations to stress, cognitive decline, and other pathophysiological processes during aging.

The effect of turbation on zinc relocation in a vertical floodplain soil profile.

Turbation is hypothesized to affect the redistribution of heavy metals in polluted floodplain soils by effects on mobility. This hypothesis was tested in microcosms by turbation of zinc-spiked sediment top layers. Manual turbation caused a fast decrease of the zinc content in the upper 15 cm of the soil, even though turbation was only applied to the upper two centimetres. It was especially zinc attached to colloid and organic matter particles that was redistributed from the top layer. Percolation processes resulted in the attached zinc being drained to depths of more than 15 cm. The decrease in zinc content of the topsoil was even stronger in combination with inundation. No indications were found for the redistribution of zinc as a result of an increase of the extractability with 0.01 M CaCl2 or changes in pH. The findings suggest that mechanical turbation and bioturbation may redistribute heavy metals from topsoils in polluted floodplains just after inundation as observed in these turbation experiments.

Cloning, expression, and regulation of a glucocorticoid-induced receptor in rat brain: effect of repetitive amphetamine.

Behavioral sensitization to psychostimulants involves neuroadaptation of stress-responsive systems. We have identified and sequenced a glucocorticoid-induced receptor (GIR) cDNA from rat prefrontal cortex. The full-length GIR cDNA encodes a 422 amino acid protein belonging to G-protein-coupled receptor superfamily. Although the ligand for GIR is still unknown, the dendrogram construction indicates that GIR may belong to peptide receptor subfamily (e.g., substance P receptor), with more distant relationship to subfamilies of glycoprotein hormone receptors (e.g., thyrotropin receptor) and biogenic amine receptors (e.g., dopamine receptor). GIR shares 31-34% amino acid identity to the tachykinin receptors (substance P receptor, neurokinin A receptor, and neurokinin B receptor). GIR mRNA is expressed preferentially in brain, and its neuronal expression is relegated to limbic brain regions, particularly in forebrain. GIR transcript levels are increased significantly and persistently in prefrontal cortex for 7 d after discontinuation of chronic amphetamine exposure. The induction of GIR expression by amphetamine is associated with augmented behavioral activation. These findings suggest that modulation of GIR expression may be involved in behavioral sensitization, and GIR may play a role at the interface between stress and neuroadaptation to psychostimulants.

Expression of the glucocorticoid-induced receptor mRNA in rat brain.

The glucocorticoid-induced receptor (GIR) is an orphan G-protein-coupled receptor awaiting pharmacological characterization. GIR was originally identified in murine thymoma cells, and shows a widespread, yet not completely complementary distribution in mouse and human brain. Expression of the mouse GIR gene is modulated by dexamethasone in the brain and periphery, suggesting that GIR function is directly responsive to glucocorticoid signals. The rat GIR was cloned from rat prefrontal cortex by our group and was shown to be up-regulated following chronic amphetamine. The physiological role of GIR in the rat is not known at present. In order to gain a clearer understanding of the potential functions of GIR in the rat, we performed a detailed mapping of GIR mRNA expression in the rat brain. GIR mRNA showed widespread distribution in forebrain limbic and thalamic structures, and a more restricted distribution in hindbrain areas such as the spinal trigeminal nucleus and the median raphe nucleus. Areas with moderate to high levels of GIR include olfactory regions such as the nucleus of olfactory tract, hippocampus, various thalamic nuclei, cortical layers, and some hypothalamic nuclei. In comparison with previous studies, significant regional differences exist in GIR distribution in mouse and rat brain, particularly in the thalamus, striatum and in hippocampus at a cellular level. Overall, the expression of GIR in rat brain more closely approaches that seen previously in human than mouse, suggesting that rat models may be more informative for understanding the role of GIR in glucocorticoid physiology and glucocorticoid-related disease states. GIR mRNA distribution in the rat indicates a potential role of this receptor in the control of feeding and ingestive behavior, regulation of stress and emotional behavior, learning and memory, and, drug reinforcement and reward.

Localization and regulation of glucocorticoid and mineralocorticoid receptor messenger RNAs in the hippocampal formation of the rat.

Messenger RNAs coding for glucocorticoid (GR) and mineralocorticoid (MR) receptor proteins were localized to discrete subfields of the hippocampal formation by in situ hybridization histochemistry, using cRNA probes of approximately equivalent specific activity. Both GR and MR mRNAs were present in all subfields examined; GR mRNA was of greatest abundance in CA1, while MR mRNA was most densely labeled in CA3. In all subfields examined, MR mRNA was considerably more abundant than GR mRNA. Removal of circulating glucocorticoids by adrenalectomy precipitated an up-regulation of GR mRNA in subfields CA1-2 and the dentate gyrus, which was reversed by dexamethasone replacement. High doses of dexamethasone significantly down-regulated GR mRNA in CA3. In contrast, adrenalectomy produced significant up-regulation of MR mRNA only in subfield CA1-2. The data indicate that steroid receptor mRNAs are differentially distributed in hippocampus, and that sensitivity to steroids occurs within defined structural domains of the hippocampal formation.