Showing papers by "Bruce S. McEwen published in 1989"
TL;DR: The diurnal variation of serum corticosterone in intact rats is correlated with a circadian regulation of type I receptor binding in the hippocampus, while MR (type I) mRNA expression is unaffected, and the changes in type I and type II receptor binding capacity elicited by differing steroid conditions cannot be attributed to modulation of the steady state levels of MR or GR mRNA.
Abstract: In the rat brain, the binding of corticosterone is mediated through two receptor types, the type I receptor and the type II receptor, which are presumed to be encoded by genes designated as MR and GR, respectively. We have studied the regulation of these receptors by glucocorticoids, utilizing a cytosol receptor binding assay. In addition, we have employed molecular probes for the GR and the MR to measure receptor mRNAs. The level of type II receptor binding is uniform across several brain regions, as is the expression of GR (type II) mRNA. In contrast, type I receptor binding is concentrated in the hippocampus, and the MR (type I) mRNA similarly shows a higher level of expression in hippocampus than in the other brain regions studied. Removal of endogenous glucocorticoids by adrenalectomy (ADX) induces an increase, and corticosterone administration results in a decrease, in the level of type I and type II binding in the hippocampus; however, no significant changes in the MR (type I) or GR (type II) mRNA levels are seen with these treatments. The diurnal variation of serum corticosterone in intact rats is correlated with a circadian regulation of type I receptor binding in the hippocampus, while MR (type I) mRNA expression is unaffected. Thus, the changes in type I and type II receptor binding capacity elicited by differing steroid conditions cannot be attributed to modulation of the steady state levels of MR (type I) or GR (type II) mRNA.
207 citations
TL;DR: Two ovarian hormones, estradiol and progesterone, which facilitate mating behavior in the female rat by acting on the ventromedial nuclei of the hypothalamus, induce changes in oxytocin receptor binding in this brain region, and the sequential actions of two ovarian hormones bring a neuropeptide and its receptors into register and enable the neuropeptic to exert behavioral effects.
Abstract: Two ovarian hormones, estradiol and progesterone, which facilitate mating behavior in the female rat by acting on the ventromedial nuclei (VMN) of the hypothalamus, induce changes in oxytocin receptor binding in this brain region. Estradiol induced a 4-fold increase in the oxytocin receptor binding of the VMN and surrounding area and increased the number and immunostaining of oxytocin fibers in an area lateral to the ventral VMN. Progesterone, in estrogen-primed rats, caused the induced oxytocin receptors to spread over the area containing the oxytocin fibers. Infusion of oxytocin into the ventromedial hypothalamus increased the display of lordosis behavior only in females primed with both estradiol benzoate and progesterone. Thus, the sequential actions of two ovarian hormones bring a neuropeptide and its receptors into register and enable the neuropeptide to exert behavioral effects.
131 citations
TL;DR: Results suggest that estrogens may regulate the activity of specific hippocampal neurons by modulating their sensitivity to GABA.
103 citations
TL;DR: In this article, the distribution of OT receptors within the ventromedial hypothalamic nucleus (VMN) was described, and the authors found that ovarian steroids sensitize the brain to OT by increasing OT receptor binding in certain brain areas involved in the regulation of female sexual behavior.
Abstract: Oxytocin (OT) neurotransmission plays a role in the facilitation of steroid-dependent sexual receptivity in the rat. One way in which the ovarian steroid 17 beta-estradiol (E2) has been shown to modulate OT transmission is by increasing OT receptor binding in certain brain areas involved in the regulation of female sexual behavior such as the ventromedial hypothalamic nucleus (VMN). This study was undertaken to describe the distribution of OT receptors within the VMN that are regulated by physiological levels of E2. With quantitative autoradiographic methods, we measured [3H]OT binding in ovariectomized female rats implanted with Silastic capsules containing cholesterol, 5% E2, or 100% E2. In addition, plasma E2 levels, pituitary progestin receptor binding, and uterine weights were measured in animals from each treatment group. Results of this study showed that physiological levels of E2 increased [3H]OT binding in caudal regions of the ventrolateral VMN and stimulated maximal uterine growth and pituitary progestin receptor binding. However, in more rostral VMN sections, E2 induced a dose-dependent increase in [3H]OT binding. These data suggest that ovarian steroids sensitize the brain to OT by increasing OT receptor binding in certain brain areas involved in the regulation of sexual receptivity.
101 citations
TL;DR: Results suggest that E and P affect muscimol binding by different mechanisms, as both hormones facilitate female reproductive behavior as well as the release of luteinizing hormone.
Abstract: The regulation of 3H-muscimol binding to high-affinity GABAa receptors by estradiol (E) and by progesterone (P) was studied within discrete brain regions using in vitro quantitative autorad
97 citations
TL;DR: The expression of GFAP throughout the brain appears to be physiologically regulated by adrenal glucocorticoids.
88 citations
TL;DR: Results are consistent with the hypothesis that steroid modulation of OT receptor binding is necessary for the induction of sexual receptivity.
Abstract: Oxytocin (OT) transmission is involved in the steroid-dependent display of sexual receptivity in rats. One of the biochemical processes stimulated by the ovarian steroid 17β- estradiol (E2) that is relevant to reproduction is the induction of OT receptor binding in the ventromedial hypothalamic nucleus (VMN). The purpose of these experiments was to determine if E2-induced changes in OT receptor binding in the VMN occur within a time frame relevant to cyclic changes in ovarian steroid secretion. OT receptor binding was measured in the VMN of ovariectomized rats implanted for 0–96 h with E2-containing Silastic capsules. The rate of decay of OT receptor binding was measured in another group of animals 6–48 h after capsule removal. Receptors were labeled with the specific OT receptor antagonist [125I]d(CH2)5[Tyr(Me)2, Thr4, Tyr-NH2 9]OVT, and binding was measured with quantitative autoradiographic methods. In addition, plasma E2 levels and uterine weights were assessed in animals from each treatment ...
80 citations
TL;DR: The results suggest that a dose of EB which activates female sexual behavior in female but not in male rats is able to induce similar levels of OT binding in the VMN of animals of both sexes.
Abstract: It has been suggested that estradiol and oxytocin (OT) may interact as neuroendocrine components in the regulation of sexual behavior. In the present study the effect of estradiol benzoate (EB) treatm
69 citations
TL;DR: This review describes the modulation of the GABAa receptor by steroid hormones and barbiturates and proposes guidelines for further research on the basis of considerable evidence to understand the molecular mechanisms by which steroid hormones modulate the receptor.
Abstract: This review describes the modulation of the GABAa receptor by steroid hormones and barbiturates and proposes guidelines for further research. Having examined the complex organization of the GABAa receptor complex and the multiple allosteric interactions between its drug and transmitter/modulator binding sites, the possibility that conformational changes of the receptor molecule may explain most of its characteristics is explored. On the basis of considerable evidence, we propose that the GABAa receptor may adopt as many as five different conformations. However, the heterogeneity of central GABAa receptor binding cannot only be explained by different configurations of a single protein. It also has been shown that different GABAa receptor subtypes exist within different brain regions. These receptor subtypes may differ from each other in their subunit composition. By describing the GABAa receptor as a macromolecular complex that may adopt different conformations and whose subunit composition may vary, it becomes possible to understand the molecular mechanisms by which steroid hormones modulate the receptor. This has led to two models of hormone actions. A first model addresses the direct effects that steroids exert on the GABAa receptor and predicts that steroid hormones may cause the conformation of the receptor complex to change between active and inactive states. A second model, which addresses the observed heterogeneity of GABAa receptor binding within the brain, suggests that steroid hormones may change the expression of the different subunits of the receptor complex by acting at the genomic level. This review complements other recent reviews describing the modulation of the GABAa receptor (Olsen and Venter, 1986; Gee, 1988).
66 citations
TL;DR: With the use of [3H]p-aminoclonidine (PAC), alpha 2-adrenergic binding sites were mapped in the brain of the Japanese quail and no sexual dimorphism in density of receptor binding was identified.
66 citations
TL;DR: AVP actions appear to involve interactions between several second- messenger systems and suggest a biochemical mechanism by which AVP exerts its centrally mediated behavioral effects.
Abstract: This study explored an effector mechanism associated with the arginine vasopressin (AVP) recognition site in the hippocampus, namely, potentiation of norepinephrine (NE)-induced cAMP accumulation in the surviving hippocampal slice. The biochemical mechanisms that underlie the AVP potentiation were investigated as follows: First, the actions of AVP upon NE-induced accumulation of cAMP in hippocampal slices from rat brain were specific to AVP and not shared by other closely related peptides, namely, oxytocin and AVP4–9. Second, the AVP-induced neuromodulation involved beta-adrenergic receptors, with AVP having no effect on cAMP levels in the absence of NE. Third, the potentiation by AVP was biphasic, with lower AVP concentrations potentiating NE-induced cAMP accumulation, while higher concentrations did not potentiate. Fourth, an antagonist of V1-type AVP receptors blocked AVP potentiation. Fifth, AVP potentiation was dependent upon extracellular calcium concentrations. Sixth, AVP potentiation was blocked by 50 microM trifluoperazine, which is consistent with a calcium-calmodulin involvement but which might also implicate protein kinase C. These alternatives and the nature of the calcium involvement are discussed. AVP actions thus appear to involve interactions between several second- messenger systems and suggest a biochemical mechanism by which AVP exerts its centrally mediated behavioral effects.
TL;DR: The results suggest that DES women show less orientation toward parenting than the controls, and there were no consistent group differences in other domains of gender-role behavior.
TL;DR: The results suggest that ovarian steroids, and benzodiazepines to a lesser extent, modulate 3H muscimol binding but do so in different brain regions, which is consistent with a genomic controlled activity.
Abstract: The levels of gamma amino butyric acid (GABAA) receptors (i.e. 3H-Muscimol binding sites) were determined by quantitative neurotransmitter receptors autoradiography in ovariectomized (OVX), OVX-estradiolo (E), OVX-progesterone (P), OVX-E + P, diazepam (DZ) and DZ + Ro15-1788 treated female hamsters. The various hormonal treatments altered 3H muscimol binding in many brain areas, whereas DZ and DZ + Ro15-1788 had little influence on GABAA receptor levels at the onset of the blocked aggressive behavioral activity. For example, E, P and E + P all significantly increased 3H muscimol binding in medial preoptic area, ventromedial hypothalamic nuclei, and vertical diagonal bandmedial septal nucleus, whereas P treatment increased binding in the caudate-putamen and decreased it in reuniens nucleus of the thalamus. E and E + P treatments increased 3H muscimol binding in the corticomedial amygdala nucleus and hippocampus. Diazepam treatment decreased the GABAA receptor binding in the caudate-putamen and basolateral amygdala, while having no effect in the other brain regions where hormone treatment was effective. In vitro incubation of brain sections with micromolar concentrations of E or P did not change muscimol binding. These results suggest that ovarian steroids, and benzodiazepines to a lesser extent, modulate 3H muscimol binding but do so in different brain regions. The hormone effects on 3H muscimol binding in the critical reproductive centres at a time period that coincides with the onset of its behavioral effect is consistent with a genomic controlled activity.
TL;DR: Results of this study show that TP increased [3H]-OT binding up to 5-fold in the ventrolateral VMN and 4-foldIn the bed nucleus of the stria terminalis and in addition [Thr4,Gly7]OT completely displaced [3D]OT binding in the VMN indicating that binding in this brain region was specific to OT receptors.
Abstract: Oxytocin (OT) binding sites are modulated by estrogens in several brain regions including the ventromedial hypothalamic nucleus (VMN) in both male and female rats. To further study steroid regulation of OT receptor binding, we examined the effect of androgen replacement in castrated male rats on OT binding with quantitative autoradiographic methods. Castrated adult male rats were treated with either 250 micrograms testosterone propionate (TP) or oil for 2 days and killed 48 h after the last injection. Brain sections through the preoptic area and VMN were labeled with 5.0 nM[3H]-OT +/- 5.0 microM unlabeled OT or 1.0 microM[Thr4,Gly7]OT and apposed to tritium-sensitive film for 7 weeks. Results of this study show that TP increased [3H]-OT binding up to 5-fold in the ventrolateral VMN and 4-fold in the bed nucleus of the stria terminalis. In addition [Thr4,Gly7]OT completely displaced [3H]-OT binding in the VMN indicating that binding in this brain region was specific to OT receptors. Because estrogens also increase OT receptor binding in male rats, it is possible that TP affects OT binding after being converted by aromatase to estradiol.
TL;DR: Results are consistent with the proposal that P may alter GABAergic inhibitory activity via changes in the levels of GABAA receptors in certain forebrain areas in the female hamster, changes which may be linked to the mediation of anxiolytic effects and to the inhibition of aggressive behavior.
Abstract: Quantitative receptor autoradiography was applied to evaluate the effects of one and three injections of 1 mg progesterone (P) on 3H muscimol binding levels in the different forebrain areas of the female hamster. The overall effect of P resulted in substantial increases in 3H muscimol binding in brain areas containing gonadal steroid receptors: medial preoptic area and ventromedial hypothalamic nucleus as well as in bed nucleus stria terminalis and subiculum. Similarly, the caudate putamen, a region where gonadal steroid receptors are not abundant, also showed substantial increases of 3H muscimol binding receptor levels. Moreover, female hamsters treated with P for 3 days presented altered 3H muscimol binding levels in the amygdala and thalamic nucleus that were, in some cases, not produced by one dose of P. P treatment also decreased GABAA binding in two areas of the thalamus. These results are consistent with the proposal that P may alter GABAergic inhibitory activity via changes in the levels of GABAA receptors in certain forebrain areas in the female hamster, changes which may be linked to the mediation of anxiolytic effects and to the inhibition of aggressive behavior. These data also suggest that P treatment increases the binding of high affinity GABA receptors in some forebrain sites and may be responsible for maintenance of the anxiolytic effects.
TL;DR: The neuroanatomical distribution of α1-adrenergic receptors was studied in Japanese quail by quantitative in vitro autoradiography using the specific antagonist [3H]prazosin as the ligand as mentioned in this paper.
Abstract: The neuroanatomical distribution of α
1-adrenergic receptors was studied in Japanese quail by quantitative in vitro autoradiography using the specific antagonist [3H]prazosin as the ligand. The presence of saturable (Bmax <200 fmol/mg protein) high affinity (Kd < 0.12 nM) binding sites was detected by saturation analysis. High concentrations of [3H]prazosin binding sites were detected in the archistriatum/pars ventralis, the hippocampus, the cortex piriformis, the area corticoidea dorsolateralis, the dorsal thalamus, and the nucleus praetectalis. Lower concentrations were seen in the intercollicular nucleus, the lateral septum, and the posterior and tuberal hypothalamus. Very little binding was seen in the preoptic and anterior hypothalamic areas. The relatively high number of binding sites identified in the telencephalic structures agrees well with previous mammalian studies. This is in contrast with the pattern in the anterior hypothalamus where, in mammals, a number of nuclei have been reported to contain a high receptor density.
TL;DR: There was no correlation between [3H]aldosterone binding and (Na+K)-ATPase activity in brain punches in rats treated with deoxycorticosterone in doses that elicited a salt appetite, and further experiments are needed to ascertain if (Na-ATPases changes in discrete areas of the brain containing moderate levels of mineralocorticoid receptors, are related to the behavioral effects of DOC.
TL;DR: The results suggest that NE modulation of Lordosis in the guinea pig is not exerted solely through progestin receptors or estrogen receptors, and it is apparent that the NE system modulates some nonhormonal component of lordosis in guinea pigs.
Abstract: Manipulations of the alpha noradrenergic (NE) system affect both lordosis and the concentration of hypothalamic steroid receptors. The present studies explored whether NE affects lordosis in guinea pigs via changes in hypothalamic estrogen or progestin receptors or through some other mechanism. The alpha 1 NE antagonist prazosin blocked lordosis which was induced with estradiol benzoate (EB) followed by progesterone (P), lordosis which was induced by EB alone and lordosis which is not dependent upon gonadal hormones for its display. These results suggest that NE modulation of lordosis in the guinea pig is not exerted solely through progestin receptors or estrogen receptors. Because prazosin blocked hormonally-independent lordosis, it is apparent that the NE system modulates some nonhormonal component of lordosis in guinea pigs.
TL;DR: It is suggested that although estrogen regulates TH in the adult MBH, this hormone does not play a role in developmental regulation of TH in this brain region, and depolarizing signals appear to be a widespread mechanism for regulation ofTH in numerous neuronal populations.
TL;DR: Cytosolic progestin receptors were measured in microdissected nuclei of the hypothalamus and preoptic area of male and female guinea pigs and showed no difference between oil treated males and oil treated females in any brain areas examined.
01 Jan 1989
TL;DR: Progestin receptor induction is higher in female VMN than in male VMN, whereas oxytocin receptor is the same in males and females, and this finding is discussed in terms of other evidence regarding sex differences in the VMN.
Abstract: Steroid hormones act upon the brain to reversibly alter structure and function of adult neural tissue and to influence behavior. They also act irreversibly during development to alter the structure and function of the neural substrate upon which these same hormones act reversibly in adult life. These principles are illustrated by feminine mating behavior in the rat, which is governed by estradiol (E) and progesterone (P) action on a small number of neurons within the ventromedial hypothalamic nuclei (VMN) of female rats. Males do not usually show feminine mating behavior, even after priming with E+P, unless they are castrated perinatally; and females given testosterone perinatally become refractory to E+P activation of feminine mating behavior in adulthood. The VMN displays two neurochemical features related to feminine mating behavior, namely, E induction of receptors for P and of receptors for the neuropeptide, oxytocin, and these are the subject of this article. Oxytocin receptors and oxytocin immunoreactivity are significantly induced by E priming prior to P exposure, and P treatment after E priming causes the oxytocin receptors to spread into the zone occupied by oxytocin immunoreactivity. These effects appear to be significant because oxytocin is able to increase feminine mating behavior in rats primed with E+P. Progestin receptor induction is higher in female VMN than in male VMN, whereas oxytocin receptor is the same in males and females. This finding is discussed in terms of other evidence regarding sex differences in the VMN.
TL;DR: While sodium excretion and plasma sodium levels were comparable in the two groups, the angiotensinogen mRNA was reduced by hypophysectomy in several limbic brain regions as well as in the liver, suggesting that reduced salt intake in response to manipulations of the body sodium and renin-angiotens in system in Hypophysectomized rats may result from decreased angiotenogen mRNA levels.
Abstract: Hypophysectomized and pituitary-intact rats were tested for their expression of salt hunger under a variety of experimental conditions. The results show that hypophysectomized rats ingest less salt in response to salt hunger induced by sodium depletion, captopril or angiotensin in comparison to pituitary-intact rats. In contrast, both groups ingest the same amount of salt in response to mineralocorticoid-induced salt hunger. While sodium excretion and plasma sodium levels were comparable in the two groups, the angiotensinogen mRNA was reduced by hypophysectomy in several limbic brain regions as well as in the liver. These results suggest that reduced salt intake in response to manipulations of the body sodium and renin-angiotensin system in hypophysectomized rats may result from decreased angiotensinogen mRNA levels.
01 Jan 1989