Biomedical subjects

R S Ahima

Publications and source records attributed to R S Ahima.

At least 37 records · Page 2Linked to original sources

PubMed1998

Distributions of leptin receptor mRNA isoforms in the rat brain.

Leptin, secreted by white adipocytes, has profound feeding, metabolic, and neuroendocrine effects. Leptin acts on the brain, but the specific anatomic sites and pathways responsible for mediating these effects are still unclear. We have systematically examined distributions of mRNA of leptin receptor isoforms in the rat brain by using a probe specific for the long form and a probe recognizing all known forms of the leptin receptor. The mRNA for the long form of the receptor (OB-Rb) localized to selected nuclear groups in the rat brain. Within the hypothalamus, dense hybridization was observed in the arcuate, dorsomedial, ventromedial, and ventral premamillary nuclei. Within the dorsomedial nucleus, particularly intense hybridization was observed in the caudal regions of the nucleus ventral to the compact formation. Receptors were preferentially localized to the dorsomedial division of the ventromedial nucleus. Hybridization accumulated throughout the arcuate nucleus, extending from the retrochiasmatic region to the posterior periventricular region. Moderate hybridization was observed in the periventricular hypothalamic nucleus, lateral hypothalamic area, medial mammillary nucleus, posterior hypothalamic nucleus, nucleus of the lateral olfactory tract, and within substantia nigra pars compacta. Several thalamic nuclei were also found to contain dense hybridization. These groups included the mediodorsal, ventral anterior, ventral medial, submedial, ventral posterior, and lateral dorsal thalamic nuclei. Hybridization was also observed in the medial and lateral geniculate nuclei. Intense hybridization was observed in the Purkinje and granular cell layers of the cerebellum. A probe recognizing all known forms of the leptin receptor hybridized to all of these sites within the brain. In addition, intense hybridization was observed in the choroid plexus, meninges, and also surrounding blood vessels. These findings indicate that circulating leptin may act through hypothalamic nuclear groups involved in regulating feeding, body weight, and neuroendocrine function. The localization of leptin receptor mRNA in extrahypothalamic sites in the thalamus and cerebellum suggests that leptin may act on specific sensory and motor systems. Leptin receptors localized in nonneuronal cells in the meninges, choroid plexus, and blood vessels may be involved in transport of leptin into the brain and in the clearance of leptin from the cerebrospinal fluid.

Adipocytes↗

PubMed1998

Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding. Implications for energy homeostasis and neuroendocrine function.

Leptin is thought to regulate energy balance through effects on food intake and thermogenesis. In addition, leptin may serve as a mediator of the neuroendocrine response to starvation, and may modulate the stress response and the timing of puberty. A role for leptin in development is suggested by the presence of neuroendocrine and structural neuronal abnormalities in ob/ob mice with genetic leptin deficiency. Here, we sought to determine the ontogeny of leptin expression and its relationship to the developing neuroendocrine axis. Leptin increased 5-10-fold in female mice during the second postnatal week independent of fat mass, and declined after weaning. The rise in leptin preceded the establishment of adult levels of corticosterone, thyroxine, and estradiol. In contrast to adult mice, leptin was not acutely regulated by food deprivation during the early postnatal period. Circadian rhythms of leptin, corticosterone, and thyroxine were regulated by food intake in adult mice. When ad libitum feeding was restricted to the light cycle, peak corticosterone levels were shifted to the beginning of the light cycle and coincided with the nadir of leptin. The inverse relationship between leptin and corticosterone was maintained such that a rise in leptin after feeding was associated with a decline in corticosterone. To determine whether changes in corticosterone during food restriction are mediated by leptin, we compared the patterns of corticosterone levels among ob/ob, db/db, and lean mice. Despite their higher basal levels of corticosterone, leptin deficiency in ob/ ob mice did not prevent the nocturnal rise in corticosterone. In contrast, the nocturnal surge of corticosterone was blunted in db/db mice. Therefore, it is likely that factors in addition to leptin are involved in the regulation of the circadian rhythm of corticosterone. The temporal relationship between leptin and other hormones in neonatal and adult mice suggests that leptin is involved in the maturation and function of the neuroendocrine axis.

Animals↗

PubMed1998

Leptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei.

Leptin has profound effects on feeding, metabolism, and neuroendocrine status. Evidence indicates that the hypothalamus coordinates these responses, though the specific brain pathways engaged by leptin remain obscure. The paraventricular nucleus of the hypothalamus (PVH) regulates pituitary gland function and feeding, and innervates autonomic preganglionic neurons, making it a candidate to regulate many of the responses to leptin. The subparaventricular zone, an anterior hypothalamic region receiving dense innervation from the suprachiasmatic nucleus, is thought to integrate circadian and metabolic information. We investigated the distribution of neurons in the rat brain activated by leptin administration that also project to the PVH or the subparaventricular zone by coupling immunohistochemistry for Fos with retrograde transport of cholera toxin-b. Intravenous leptin characteristically activated several cell groups including the ventromedial hypothalamic nucleus, the dorsomedial hypothalamic nucleus (DMH), and the PVH. When tracer injections were centered in the subparaventricular zone, many double-labeled cells were observed in the dorsomedial subdivision of the ventromedial hypothalamic nucleus. This projection may provide an anatomic substrate for integration of metabolic and circadian information to regulate the hypothalamo-pituitary axis. When cholera toxin-b injections were centered in the PVH, many double-labeled cells were found within the caudal DMH. Hence, activation of specific neuroendocrine and autonomic elements of the PVH may be triggered by leptin-activated afferents arising in the DMH. Our results demonstrate that a discrete set of hypothalamic pathways may underlie leptin's autonomic, endocrine, and behavioral effects.

Animals↗

PubMed1998

Leptin activates hypothalamic CART neurons projecting to the spinal cord.

The adipocyte-derived hormone leptin decreases body weight in part by activating the sympathetic nervous system, resulting in increased thermogenesis and energy expenditure. We investigated hypothalamic pathways underlying leptin's effects on stimulating the sympathetic nervous system. We found that leptin activates neurons in the retrochiasmatic area (RCA) and lateral arcuate nucleus (Arc) that innervate the thoracic spinal cord and also contain cocaine- and amphetamine-regulated transcript (CART). We also found that most CART-containing neurons in the RCA and Arc of the hypothalamus also contain proopiomelanocortin (POMC) mRNA. The finding that leptin activates CART/POMC neurons innervating sympathetic preganglionic neurons in the thoracic spinal cord suggests that this pathway may contribute to the increased thermogenesis and energy expenditure and decreased body weight observed following leptin administration.

Animals↗

PubMed1998

Arcuate nucleus ablation prevents fasting-induced suppression of ProTRH mRNA in the hypothalamic paraventricular nucleus.

Fasting results in reduced thyroid hormone levels and inappropriately low or normal thyroid-stimulating hormone (TSH), partly attributed to central hypothyroidism due to suppression of pro TRH gene expression in the hypothalamic paraventricular nucleus. Recently, we demonstrated that the systemic administration of leptin to fasting animals restores plasma thyroxine (T4) and proTRH mRNA in the paraventricular nucleus to normal, suggesting that the fall in circulating leptin levels during fasting acts as a signal to hypophysiotropic neurons in the paraventricular nucleus to reset the set point for feedback regulation of pro TRH mRNA by thyroid hormone. To determine whether the effect of fasting on the hypothalamic-pituitary-thyroid axis is mediated through the hypothalamic arcuate nucleus where leptin receptors are highly concentrated, we studied the effect of fasting and exogenous leptin administration on plasma thyroid hormone levels and proTRH mRNA concentration in the paraventricular nucleus in adult animals with arcuate nucleus lesions induced pharmacologically by the neonatal administration of monosodium L-glutamate (MSG). In normal animals, fasting reduced plasma T4 and TSH levels and the concentration of proTRH mRNA in the hypothalamic paraventricular nucleus. In contrast, neither fasting nor leptin administration to fasting MSG-treated animals had any significant effects on plasma thyroid hormone and TSH levels and proTRH mRNA in the paraventricular nucleus. These studies suggest that during fasting, the arcuate nucleus is essential for the normal homeostatic response of the hypothalamic-pituitary-thyroid axis and may serve as a critical locus to mediate the central actions of leptin on proTRH gene expression in the paraventricular nucleus.

Animals↗

PubMed1998

Expression of leptin receptor isoforms in rat brain microvessels.

Leptin acts on specific brain regions to affect body weight regulation. As leptin is made by white adipose tissue, it is thought that leptin must cross the blood-brain barrier or the blood-cerebrospinal fluid barrier to reach key sites of action within the brain. High expression of a short form leptin receptor has been reported in the choroid plexus. However, whether one or more of the known leptin receptor isoforms is expressed in brain capillaries is unknown. To identify and quantitate leptin receptor isoforms in rat brain microvessels, we applied quantitative RT-PCR to RNA from purified rat brain microvessels in parallel with in situ hybridization. The results show that the amount of short form leptin receptor messenger RNA (mRNA) in brain microvessels is extremely high, exceeding that in choroid plexus. In contrast, low levels of this mRNA were detected in the cerebellum, hypothalamus, and meninges. The long form leptin receptor mRNA is only present at low levels in the microvessels, but surprisingly, its level in cerebellum is 5 times higher than that in the hypothalamus. In situ hybridization experiments confirmed strong expression of short leptin receptors in microvessels, choroid plexus, and leptomeninges. The distribution and type of leptin receptor mRNA isoforms in brain microvessels are consistent with the possibility that receptor-mediated transport of leptin across the blood-brain barrier is mediated by the short leptin receptor isoform.

Animals↗

PubMed1997

Endocrine function of neuropeptide Y knockout mice.

Among its many proposed functions, neuropeptide Y (NPY) is thought to modulate the hypothalamic-pituitary axis. Specifically, increased hypothalamic NPY signaling may be critical in mediating the neuroendocrine response to fasting. To determine the consequences of NPY deficiency on endocrine physiology, multiple hormones were quantitated in wildtype and NPY-knockout mice under fed and fasted conditions. Serum concentrations of leptin, corticosterone, thyroxine, and testosterone were normal in NPY-knockout males fed ad libitum. A 48-hour fast resulted in a 50% reduction in leptin, a 60% reduction in thyroxine, a 75% reduction in testosterone, and a 12-fold increase in corticosterone in both wildtype and NPY-knockout mice. Fasting also increased the estrous cycle length by 3 days in both wildtype and NPY-deficient female mice. We conclude that NPY is not essential for appropriate function of the gonadotropic, thyrotropic, or corticotropic axes under ad lib fed conditions or in response to acute fasting.

Animals↗

PubMed1997

Leptin accelerates the onset of puberty in normal female mice.

The fat-derived hormone, leptin, is proposed to serve as an adipostatic signal to the brain to reduce food intake and body weight. In addition to its effects on body weight, chronic leptin treatment restores puberty and fertility to ob/ob mice with total leptin deficiency, and acute treatment substantially corrects hypogonadism in mice starved for 2 d without affecting body weight. Leptin may therefore be a critical signal, linking adiposity and reproduction. Since body weight and adiposity appear to play a critical role in the timing of puberty in humans and rodents, and leptin levels rise with increasing adiposity, we studied the effects of once daily injections of recombinant leptin on the onset of puberty in female mice weaned on day 21 and fed ad libitum. There was a linear increase in body weight during the study period, which was not altered by the dose of leptin used. Mice injected with leptin had an earlier onset of three classic pubertal parameters (i.e., vaginal opening, estrus, and cycling) compared with saline-injected controls. Leptin is the first peripheral molecule demonstrated to accelerate the maturation of the reproductive axis in normal rodents. We propose that leptin is the signal that informs the brain that energy stores are sufficient to support the high energy demands of reproduction, and may be a major determinant of the timing of puberty.

Animals↗

PubMed1997

Leptin activates neurons in ventrobasal hypothalamus and brainstem.

Leptin is a circulating protein secreted by adipocytes which has profound feeding, metabolic, and neuroendocrine effects. Leptin receptors have been localized to the hypothalamus, but the anatomic sites responsible for mediating the effects of circulating leptin have not been demonstrated. We report that systemic administration of leptin activates nuclear groups in the ventrobasal hypothalamus, including the ventromedial, dorsomedial, and ventral premammillary hypothalamic nuclei. Leptin also activated the parvicellular subdivisions of the paraventricular hypothalamic nucleus that project to parasympathetic and sympathetic preganglionic neurons. Finally, leptin administration activated the superior lateral parabrachial subnucleus, a nuclear group containing cholecystokinin neurons that project to the ventrobasal hypothalamus. These findings indicate that circulating leptin activates specific nuclear groups in the hypothalamus and brainstem known to regulate complex physiological responses during times of substrate availability.

Animals↗

PubMed1997

Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus.

Prolonged fasting is associated with a number of changes in the thyroid axis manifested by low serum T3 and T4 levels and, paradoxically, low or normal TSH. This response is, at least partly, caused by suppression of proTRH gene expression in neurons of the hypothalamic paraventricular nucleus (PVN) and reduced hypothalamic TRH release. Because the fall in thyroid hormone levels can be blunted in mice by the systemic administration of leptin, we raised the possibility that leptin may have an important role in the neuroendocrine regulation of the thyroid axis, through effects on hypophysiotropic neurons producing proTRH. Adult male, Sprague-Dawley rats were either fed normally, fasted for 3 days, or fasted and administered leptin at a dose of 0.5 microg/gm BW i.p. every 6 h. Fasted animals showed significant reduction in plasma total and free T4 and T3 levels compared with controls, that were restored toward normal by the administration of leptin. Percent free T4, but not percent free T3, increased during fasting, further suggesting a reduction in plasma transthyretin levels that did not return to fed levels after leptin administration. By semiquantitative analysis of in situ hybridization autoradiograms, proTRH messenger RNA in medial parvocellular PVN neurons was markedly suppressed in the fasting animals but was restored to normal by leptin administration [fed vs. fast vs. fast/leptin (density units x 10(8)): 8.5 +/- 0.4, 3.2 +/- 0.2, 8.1 +/- 0.8]. In contrast, proTRH messenger RNA in adjacent neurons in the lateral hypothalamus that do not have a hypophysiotropic function remained unchanged by any of the experimental manipulations. These findings indicate that leptin has a selective, central action to modulate the hypothalamic-pituitary-thyroid axis by regulating proTRH gene expression in the PVN but does not have peripheral effects on thyroid-binding proteins. We propose that the fall in circulating leptin levels during fasting resets the set point for feedback inhibition by thyroid hormones on the biosynthesis of hypophysiotropic proTRH, thereby allowing adaptation to starvation.

Animals↗

PubMed1997

Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress.

Leptin is a newly identified protein hormone that is synthesized and secreted by adipose tissue. Absence of the mature hormone is responsible for the obese phenotype of ob/ob mice. The hypothalamic-pituitary-adrenal axis (HPAA) is activated in ob/ob mice, and chronic administration of leptin to ob/ob mice decreases plasma corticosterone levels, suggesting that the adipose hormone is capable of inhibiting the HPAA. The aim of this study was to determine whether leptin feeds back acutely to inhibit the HPAA of normal mice and rats. Male C57BL mice were injected ip with 100 microl saline and 2 or 4 microg/g BW mouse leptin in saline vehicle, and 4 h later they were subjected to 2 h of restraint stress by taping the hind limbs together or no stress. Hind leg restraint stimulated the HPAA as measured by significant (P < 0.05) elevation of both ACTH and corticosterone. Pretreatment with recombinant mouse leptin blocked the stress-mediated stimulation of both plasma hormones. To determine whether this inhibition was exerted at the hypothalamic level through inhibition of CRH, we studied leptin action on isolated rat hypothalami perifused with Krebs-Ringer buffer containing glucose (5.5 mM). CRH secretion was stimulated by decreasing the glucose concentration of the buffer to 1.1 mM. A surge of CRH was released over a 2-h period (basal integrated release was 14.4 +/- 1.6 pg/2 h, n = 5 and increased to 34.7 +/- 3.1 pg/2 h, n = 14). This response was blocked by mouse leptin in a dose-dependent manner (integrated stimulated CRH secretion was 30.6 +/- 2.5 pg/2 h, n = 5; 20.5 +/- 3.6 pg/2 h, n = 7; 15.3 +/- 4.3 pg/2 h, n = 3 for 1 nM, 3 nM and 30 nM, respectively). Leptin did not alter secretion of ACTH from rat primary cultured pituitary cells. These data demonstrate that leptin can inhibit hypothalamic CRH release, either directly or indirectly through another hypothalamic neuropeptide such as neuropeptide-Y. Dysfunctional leptin, insufficient leptin levels, or leptin resistance should each result in a partial open loop, thereby accounting for elevated glucocorticoid levels that accompany and contribute to many obese phenotypes. Leptin's ability to inhibit CRH release is the likely explanation for its ability to inhibit activation of the HPAA in response to stress.

Adrenocorticotropic Hormone↗

PubMed1996

Immunohistochemical localization of hepatic nitric oxide synthase in normal and transgenic sickle cell mice: the effect of hypoxia.

Nitric oxide (NO) generated from L-arginine and molecular oxygen by nitric oxide synthase (NOS) has been shown to influence hepatocellular function and pathology in response to ischemia and certain hepatotoxins. In the present study, we examined the liver of a transgenic line of sickle cell mice for hepatocellular injury and localization of two isoforms of NOS, the endothelial constitutively expressed isoform (EcNOS) and the inducible isoform (iNOS) by immunohistochemistry. Diffuse expression of EcNOS was observed in hepatocytes of control and sickle cell animals maintained under room air conditions. In contrast, iNOS was observed only in the sickle cell mice, well-localized to hepatocytes surrounding the central veins of the lobules. When normal mice were exposed to hypoxic conditions for 4 to 5 days, iNOS immunostaining appeared de novo in a patchy distribution throughout the liver lobules. In the sickle cell mice, hypoxia appeared to increase the subjective intensity of pericentral staining of iNOS. Liver histology was normal in the sickle cell mice maintained under room air conditions, but showed multifocal areas of necrosis when sickling was exacerbated by chronic hypoxic conditions. However, a pericentral zone of preserved architecture was present, corresponding to the region of iNOS staining. We postulate that pericentral induction of iNOS under ambient conditions occurs in transgenic sickle cell mice in response to particularly intense hypoxic conditions near the central veins of the liver. Increases in NO synthesis may occur in this region, which would serve to protect these cells from ischemic damage either directly or by maintaining blood flow. These findings could be relevant to liver pathophysiology in patients with sickle cell disease.

Anemia, Sickle Cell↗

PubMed1996

Role of leptin in the neuroendocrine response to fasting.

A total deficiency in or resistance to the protein leptin causes severe obesity. As leptin levels rise with increasing adiposity in rodents and man, it is proposed to act as a negative feedback 'adipostatic signal' to brain centres controlling energy homeostasis, limiting obesity in times of nutritional abundance. Starvation is also a threat to homeostasis that triggers adaptive responses, but whether leptin plays a role in the physiology of starvation is unknown. Leptin concentration falls during starvation and totally leptin-deficient ob/ob mice have neuroendocrine abnormalities similar to those of starvation, suggesting that this may be the case. Here we show that preventing the starvation-induced fall in leptin with exogenous leptin substantially blunts the changes in gonadal, adrenal and thyroid axes in male mice, and prevents the starvation-induced delay in ovulation in female mice. In contrast, leptin repletion during this period of starvation has little or no effect on body weight, blood glucose or ketones. We propose that regulation of the neuroendocrine system during starvation could be the main physiological role of leptin.

Adrenal Glands↗

PubMed1996

Renal nitric oxide synthases in transgenic sickle cell mice.

The alpha H beta S [beta MDD] mouse is a useful model for studying renal functional abnormalities in sickle cell disease. We previously reported that these mice develop a urine concentrating defect when chronically exposed to a low oxygen environment. In the present study, we measured glomerular filtration rate (GFR), urinary excretion of NO2 s+ NO3, the stable products of nitric oxide (NO), and the abundance of endothelial constitutive nitric oxide synthase (NOS III) and inducible nitric oxide synthase (NOS II) in the kidneys by Western blot. Immunohistochemistry was also carried out. We found that GFR is significantly higher in the transgenic mice than in controls. The urinary NO2 + NO3/creatinine ratio was also higher. The Western blots revealed that both NOS III and NOS II are markedly increased in the kidneys of transgenic mice as compared to normal control mice. Immunohistochemistry localized NOS III reactivity in proximal convoluted cells in the cortex of control and alpha H beta S [beta MDD] mice. NOS II immunostaining was not seen in control mice but was clearly evident in glomeruli and distal nephron segments of the alpha H beta S [beta MDD] mice. These observations suggest that NOS II is induced in glomeruli and distal nephrons of the alpha H beta S [beta MDD] mice. An increase in synthesis of NO may occur in the glomeruli as a result of NOS II induction, and this may contribute to the hyperfiltration in these mice.

Anemia, Sickle Cell↗

PubMed1993

Differential responses to angiotensin-(1-7) in the feline mesenteric and hindquarters vascular beds.

Regional vascular responses to angiotensin (Ang)-(1-7), a heptapeptide derivative of Ang II were investigated in the feline hindquarters and mesenteric vascular beds under conditions of controlled flow. In the mesenteric vascular bed, injections of Ang-(1-7) in doses of 1, 3 and 10 micrograms produced dose-dependent decreases in mesenteric perfusion pressure whereas at doses of 30 and 100 micrograms, increases were observed. In contrast, in the hindquarters circulation, low doses produced increases while high doses produced decreases in perfusion pressure. In both vascular beds the degree of vasoconstriction was weak, being less than 1% of that elicited by Ang II. The vasoconstrictor effect of Ang-(1-7) in both the mesenteric and hindquarters vascular bed was blocked by DuP 753 (1 mg/kg i.v.), an Ang receptor subtype 1 (AT1) antagonist. The vasodilator responses in both vascular beds were partially blocked by the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (100 mg/kg i.v.) but were unaffected by the cyclooxygenase inhibitor, meclofenamate (2.5 mg/kg i.v.). The present results show that in the peripheral vascular bed of the cat, Ang-(1-7) causes vasodilation or modest vasoconstriction, depending on the dose and the regional vascular bed studied. The present data also suggest that the vasodilator effect of the peptide may be mediated in part by the release of endothelium-derived relaxing factor and the vasoconstrictor effect by activation of the AT1 receptor subtype.

Amino Acid Oxidoreductases↗

PubMed1992

Regulation of glucocorticoid receptor immunoreactivity in the rat hippocampus by androgenic-anabolic steroids.

To determine whether androgenic-anabolic steroids (AAS) regulate glucocorticoid receptors (GR), the effects of a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and boldenone undecylenate) on GR immunoreactivity (ir), were examined in hippocampi of adrenalectomized male rats. Treatment with AAS for 1 week increased nuclear GRir in pyramidal cells of CA1, and granule cells of the dentate gyrus. These findings suggest a role for GR in the mediation of some of the CNS effects of androgenic-anabolic steroids.

Adrenalectomy↗

PubMed1992

Glucocorticoid regulation of preproenkephalin gene expression in the rat forebrain.

The effects of glucocorticoids on the levels of preproenkephalin (PPE) mRNA in the rat forebrain were analyzed with in situ hybridization and dot blots. In adrenally-intact rats, high levels of PPE mRNA, as assessed by in situ hybridization, were localized in the caudate-putamen, nucleus accumbens, central amygdala, and ventrolateral ventromedial hypothalamus (VMHVL), and low levels in the hippocampus. After adrenalectomy, the density of PPE mRNA-positive cells and the level of PPE mRNA/cell were decreased in all regions except the hippocampus. Acute treatment with corticosterone (CORT) in adrenalectomized rats increased the level of PPE mRNA/cell in the caudate-putamen and VMHVL. In intact rats, chronic treatment with CORT increased the density of PPE mRNA-positive cells in the caudate-putamen and hippocampus, and the level of PPE mRNA/cell in the caudate-putamen and nucleus accumbens. The effect of chronic CORT treatment on PPE mRNA in the striatum, amygdala, hippocampus and mediobasal hypothalamus was assessed with dot blots. Chronic CORT treatment increased PPE mRNA levels in the caudate-putamen and hippocampus. There was a good correlation between results on the effect of chronic CORT treatment on PPE mRNA levels in intact rats, obtained from dot blots and in situ hybridization. Results from this study suggest that glucocorticoids are required for the maintenance of basal PPE mRNA levels in most regions of the rat forebrain. There is, however, considerable regional heterogeneity in the effect of glucocorticoid treatment on PPE mRNA levels in adrenalectomized and intact rats. Increased PPE mRNA levels in response to high circulating levels of glucocorticoids, e.g. in stress, may have important pathophysiological consequences.

Amygdala↗

PubMed1992

Type II corticosteroid receptor-like immunoreactivity in the rat cerebellar cortex: differential regulation by corticosterone.

Type II corticosteroid receptor-like immunoreactivity (type II-ir) was localized at the light- and electron-microscopic levels in the rat cerebellar cortex using BUGR2 monoclonal antibody. In intact rats, type II-ir was observed in the nuclei of basket, stellate, Golgi and Purkinje cells. After 1 week of adrenalectomy, type II-ir was barely resolvable in basket, stellate, Golgi and most Purkinje cells. Vermal Purkinje cells showed intense nuclear and cytoplasmic type II-ir. After 4 weeks of adrenalectomy, type II-ir was markedly reduced in most vermal Purkinje cells, however a few in lobules 1-3 and 9 and 10 retained diffuse immunoreactivity. Acute treatment with corticosterone restored nuclear type II-ir to basket, stellate, Golgi and Purkinje cells in the cerebellar hemispheres, flocculi and paraflocculi. In the vermis most Purkinje cells showed nuclear type II-ir following corticosterone treatment. Diffuse type II-ir was, however, retained in a few Purkinje cells in vermal lobules 1-3, 9 and 10. The distribution of GABA-like immunoreactivity (GABA-ir) in the cerebellar cortex was not altered by adrenalectomy or acute corticosterone treatment. 30-60% of type II-ir Purkinje cells in intact rats were GABA-ir. In adrenalectomized and corticosterone-treated rats, a similar proportion of type II-ir Purkinje cells were GABA-ir. The differential regulation of neuronal type II-ir in the cerebellum by corticosterone may account for some of the known effects of glucocorticoids on motor coordination.

Adrenal Glands↗