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D W Pfaff

Publications and source records attributed to D W Pfaff.

At least 91 records · Page 5Linked to original sources
PubMed1997

Preproenkephalin mRNA is regulated by an interaction between steroid hormones and nociceptive stimulation.

The expression of preproenkephalin (PPE) mRNA has previously been shown to be regulated by steroid hormones in the ventromedial nucleus of the hypothalamus (VMH) and to be regulated by noxious stimuli in the dorsal horn of the spinal cord (DH). The present in situ hybridization study in ovariectomized rats showed that PPE mRNA expression in both the VMH and the lumbar DH, responds to the interaction between a noxious peripheral stimulus and ovarian steroid hormones. In the VMH, either estradiol or estradiol + progesterone increased the mean PPE mRNA content per cell by 100% compared with vehicle-treated rats. Unilateral hindpaw injection of 5% formalin, as compared to saline, significantly increased mean PPE mRNA content per VMH cell in rats treated with vehicle or estradiol but not those treated with estradiol + progesterone. Regression analysis for mean PPE mRNA content per VMH cell as a function of intensity of hindpaw inflammation showed a significant positive correlation coefficient after vehicle and estradiol treatment (P < 0.02) but a strong trend towards a negative correlation coefficient after estradiol + progesterone treatment (P < 0.06). ANOVA for homogeneity of regression coefficients showed a significant difference across hormone groups (P < 0.01). In the lumbar DH, mean PPE mRNA content per cell was greater in rats injected with formalin than with saline and was greatest in rats given steroids + formalin. Mean PPE mRNA content per DH cell was greater ipsilateral than contralateral to the formalin injection in estradiol-treated rats, but no laterality difference was seen in the other hormone groups. No significant differences in mean PPE mRNA levels per DH cell were found among the rats treated with saline + hormone, saline + vehicle, formalin + vehicle, or uninjected rats. For all hormone groups combined, mean PPE mRNA per DH cell showed a significant positive regression on intensity of hindpaw inflammation (P < 0.05). Taken together these data are consistent with reports of increased pain threshold during pregnancy, descending control of antinociception from the basomedial hypothalamus and positive correlations between VMH levels of PPE mRNA and lordosis, a behavior evoked by somatosensory stimulation below nociceptive threshold.

Animals↗
PubMed1997

Effects of estrogen on oxytocin receptor messenger ribonucleic acid expression in the uterus, pituitary, and forebrain of the female rat.

Oxytocin receptors are regulated during parturition and lactation. Gonadal steroids are thought to be key players in this regulation. It is not well documented how oxytocin receptor gene expression is regulated in the CNS. In this study we analyzed potential estrogen effects on the oxytocin receptor mRNA levels in some areas integral to the limbic-hypothalamic system, namely the ventromedial nucleus of the hypothalamus (VMH), posterior medial nucleus of amygdala (MeAmyg), and arcuate nucleus (ARC), as well as the caudate putamen (CPu), CA1 region of the hippocampus, anterior pituitary, and uterine tissue of ovariectomized (OVX) female rats. By in situ hybridization we observed a 4.4-fold increase in oxytocin receptor mRNA levels in the VMH after 48 h of estrogen treatment when compared to OVX rats. Smaller increases were observed in the MeAmyg, hippocampus, and anterior pituitary (3.18, 1.76, and 2.55, respectively). No changes in oxytocin receptor mRNA levels were observed in the CPu or ARC after estrogen treatment. A similar finding resulted from slot-blot analysis of total mRNA extracts. In uterine tissue, 48 h of estrogen treatment increased oxytocin receptor mRNA level in the myometrium (3.13-fold). No changes in oxytocin receptor mRNA levels were observed after 12 and 24 h of estrogen treatment. These findings suggest that the estrogenic regulation of oxytocin receptor binding in both CNS and uterine tissues may in part be mediated by de novo synthesis of oxytocin receptor mRNA or by alterations in the stability of oxytocin receptor gene transcripts.

Amygdala↗
PubMed1997

Interactions of estrogen- and thyroid hormone receptors on a progesterone receptor estrogen response element (ERE) sequence: a comparison with the vitellogenin A2 consensus ERE.

The identification of hormone response elements in the promoter regions of hormonally regulated genes has revealed a striking similarity between the half-site of the estrogen-response element (ERE) and a consensus sequence constituting the thyroid hormone-response element. Because of the potential for thyroid hormone (T3) to affect estrogen (E)- and progesterone-dependent female reproductive behavior via EREs, we have begun to investigate the activity of an ERE identified in the progesterone receptor (PR) proximal promoter and its interactions with the estrogen receptor (ER) and thyroid hormone receptors (TR). In addition, we have compared ER and TR interactions on the PR ERE construct with that of the vitellogenin A2 (vit A2) consensus ERE. Electrophoretic mobility shift assays demonstrated that TR binds to the PR ERE as well as to the consensus ERE sequence in vitro. Further, these two EREs were differentially regulated by T3 in the presence of TR. T3 in the presence of TR alpha increased transcription from a PR ERE construct approximately 5-fold and had no inhibitory effect on E induction. Similarly, T3 also activated a beta-galactosidase reporter construct containing PR promoter sequences spanning -1400 to +700. In addition, the TR isoforms beta1 and beta2 also stimulated transcription from the PR ERE construct by 5- to 6-fold. A TR alpha mutant lacking the ability to bind AGGTCA sequences in vitro failed to activate transcription from the PR ERE construct, demonstrating dependence on DNA binding. In contrast to its actions on the PR ERE construct, TR alpha did not activate transcription from the vit A2 consensus ERE but rather attenuated E-mediated transcriptional activation. Attenuation from the vit A2 consensus ERE is not necessarily dependent on DNA binding as the TR alpha DNA binding mutant was still able to inhibit E-dependent transactivation. In contrast to TR alpha, the isoforms TRbeta1 and TRbeta2 failed to inhibit E-induced activation from the vit A2 consensus ERE. These results demonstrate that the PR ERE construct differs from the vit A2 consensus ERE in its ability to respond to TRs and that divergent pathways exist for activation and inhibition by TR. Since ERs, PRs, and TRs are all present in hypothalamic neurons, these findings may be significant for endocrine integration, which is important for reproductive behavior.

Animals↗
PubMed1997

Sexual reinforcement in the female rat.

Sexual reinforcement in the female rat was studied in a preparation that allowed continuous operant responding for access to a male rat leading to intromission. Experiment 1 used a high operant level nose-poke response to test the possible reinforcing effects of some components of access to a male. A simple tone stimulus used as a conditioned reinforcer and two odor stimuli, target male bedding and emulsified preputial gland, were tested. None of these contingent events altered responding above or below operant level. Access to the male, which was always accompanied by intromission, immediately increased response rate when it was made contingent upon the nose-poke response. Performance on fixed-ratio schedules was erratic, and response rate was low in comparison to typical food-reinforced responding. An interresponse-time analysis indicated, however, that some effect of the ratio contingency may have been present. In Experiment 2, several modifications of the procedure were tested with the objective of creating a more tractable preparation for behavior analysis. Response type and the hormone delivery method were changed, and 2 target males were used instead of 1. The latter tripled the average number of reinforcers earned in a single session. Differences between sexual and other reinforcers are discussed in terms of procedural, quantitative, and motivational aspects of the sexual reinforcement procedure.

Animals↗
PubMed1996

NADPH diaphorase activity and nitric oxide synthase immunoreactivity in lordosis-relevant neurons of the ventromedial hypothalamus.

The distribution of the enzymes NADPH diaphorase and nitric oxide synthase in the ventromedial nucleus of the hypothalamus of cycling and ovariectomized/estrogen-treated and control female rats was demonstrated using histochemical and immunocytochemical methods. Serial section analysis of vibratome sections through the entire ventromedial nucleus showed that NADPH diaphorase cellular staining was localized primarily in the ventrolateral subdivision. NADPH diaphorase staining was visible in both neuronal perikarya and processes. Light microscopic immunocytochemistry using affinity-purified polyclonal antibodies to brain nitric oxide synthase revealed a similar pattern of labelling within the ventromedial nucleus and within neurons of the ventrolateral subdivision of the ventromedial nucleus. Control experiments involved omitting the primary antibodies; no labelling was visible under these conditions. Some, but not all, neurons in the ventrolateral subdivision of the ventromedial nucleus contained both NADPH diaphorase and brain nitric oxide synthase as demonstrated by co-localization of these two enzymes in individual cells of this area. That NADPH diaphorase and brain nitric oxide synthase were found in estrogen-binding cells was shown by co-localization of NADPH diaphorase and estrogen receptor and brain nitric oxide synthase and estrogen receptor at the light and ultrastructural levels, respectively. Our studies suggest that brain nitric oxide synthase is present and may be subject to estrogenic influences in lordosis-relevant neurons in the ventrolateral subdivision of the ventromedial nucleus. The hypothalamus is a primary subcortical regulatory center controlling sympathetic function. Therefore, not only is nitric oxide likely to be important for reproductive behavior, but also for the regulation of responses to emotional stress and other autonomic functions.

Animals↗
PubMed1996

Thyroid hormone and estrogen interact to regulate behavior.

Environmental perturbations that increase plasma thyroid hormone (T3) concentrations also profoundly affect female reproductive behavior and physiology. We explored whether these effects were mediated by interactions between T3 receptor (TR) and estrogen receptor (ER). This hypothesis was of interest because the half-site of a consensus T3 response element DNA sequence is identical to an ER response element (ERE), and TRs bind to a consensus ERE. Molecular data presented in the accompanying paper [Zhu, Y.-S., Yen, P.M., Chin, W.W.& Pfaff, D.W. (1996) Proc. Natl. Acad. Sci. USA 93, 12587-12592] demonstrate that TRs and ERs are both present in rat hypothalamic nuclear extracts and that both can bind to the promoter the hypothalamic gene preproenkephalin and that interations between liganded TRs and ERs affect preproenkephalin transcription. In this paper, we show that molecular interactions between TRs and ERs are sufficient to mediate environmental effects on estrogen-controlled reproductive behavior. Ovariectomized (OVX) rats treated with high doses of T3 showed significantly lower levels of lordosis behavior in response to estradiol benzoate (EB) compared with OVX females treated with EB alone. Conversely, thyroidectomized/OVX females treated with EB showed significantly greater levels of lordosis behavior compared with OVX females treated with EB, showing the effect of endogenous T3. Thyroid hormone interference with EB-induced behavior could not be explained by a reduction in plasma E2 concentrations or by a general reduction in responsiveness of EB-sensitive tissues. Moreover, numbers of hypothalamic ER-immunoreactive cells increased dramatically following T3 treatment. These data suggest that T3 may reduce EB-dependent sexual behavior through interactions between TR and ER in the nuclei of behaviorally relevant hypothalamic neurons, envisioning for the first time a functional consequence of interactions between two nuclear hormone receptors in brain. These results also open up the possibility of molecular interactions on DNA encoding environmental signals, a new field for the study of neuronal integration.

Animals↗
PubMed1996

Estrogen and thyroid hormone interaction on regulation of gene expression.

Estrogen receptor (ER) and thyroid hormone receptors (TRs) are ligand-dependent nuclear transcription factors that can bind to an identical half-site, AGGTCA, of their cognate hormone response elements. By in vitro transfection analysis in CV-1 cells, we show that estrogen induction of chloramphenicol acetyltransferase (CAT) activity in a construct containing a CAT reporter gene under the control of a minimal thymidine kinase (tk) promoter and a copy of the consensus ER response element was attenuated by cotransfection of TR alpha 1 plus triiodothyronine treatment. This inhibitory effect of TR was ligand-dependent and isoform-specific. Neither TR beta 1 nor TR beta 2 cotransfection inhibited estrogen-induced CAT activity, although both TR alpha and TR beta can bind to a consensus ER response element. Furthermore, cotransfection of a mutated TR alpha 1 that lacks binding to the AGGTCA sequence also inhibited the estrogen effect. Thus, the repression of estrogen action by liganded TR alpha 1 may involve protein-protein interactions although competition of ER and TR at the DNA level cannot be excluded. A similar inhibitory effect of liganded TR alpha 1 on estrogen induction of CAT activity was observed in a construct containing the preproenkephalin (PPE) promoter. A study in hypophysectomized female rats demonstrated that the estrogen-induced increase in PPE mRNA levels in the ventromedial hypothalamus was diminished by coadministration of triiodothyronine. These results suggest that ER and TR may interact to modulate estrogen-sensitive gene expression, such as for PPE, in the hypothalamus.

Animals↗
PubMed1996

Gonadotropin-releasing hormone gene expression in teleosts.

Expression of multiple molecular forms of gonadotropin-releasing hormone (GnRH) mRNAs and GnRH peptides were examined in the brains of tilapia (Oreochromis mossambicus) and sockeye salmon (Oncorhynchus nerka), using in situ hybridization histochemistry and immunohistochemical techniques. After otherwise identical conditions, lesser background and stronger GnRH hybridization signals were observed on cryostat vs. paraffin sections. In both fresh and Bouin's-fixed paraffin-embedded tissues, there was a good correlation between the distribution of GnRH mRNA and GnRH peptide-containing cells. Although the brains of tilapia and the sockeye were immunoreactive to three forms of the GnRH molecule (salmon, mammal, chicken-II), GnRH mRNA expression was site-specific and species-specific. In the tilapia, ganglionic cells of the nucleus olfactoretinalis, basal telencephalon and the anteroventral preoptic area were immunoreactive to salmon-, and mammalian-GnRH peptide. Neurons of the nucleus olfactoretinalis expressed cichlid-GnRH I mRNA. The preoptic neurons, despite the immunoreactivity, expressed no hybridization signals. Midbrain neurons were immunoreactive to salmon-GnRH but expressed cichlid-GnRH II beta (= chicken-GnRH II) mRNA hybridization signals. In the sockeye, ganglionic cells along the extracerebral course of the nervus terminalis were immunoreactive to mammalian-, chicken-II and salmon-GnRH. These neurons expressed only salmon-GnRH mRNA hybridization signals. Intracerebral GnRH expression in the sockeye was delayed till smoltification. The basal telencephalon and midbrain neurons immunoreactive to salmon-GnRH, formed no hybridization signals with GnRH antisense probes. Oligonucleotide probes complementary to chicken-GnRH I and mammalian-GnRH revealed no hybridization signals in the tilapia and in the sockeye brain. Fibers, immunoreactive to salmon-, mammalian-, and chicken II-GnRH were seen in close association with growth hormone cells. Chicken-GnRH II-immunoreactive fibers were also seen in close proximity to somatolactin cells in the sockeye salmon.

Animals↗
PubMed1996

Continuous renewal of the axonal pathway sensor apparatus by insertion of new sensor molecules into the growth cone membrane.

BACKGROUND: Growth cones at the tips of growing axons move along predetermined pathways to establish synaptic connections between neurons and their distant targets. To establish their orientation, growth cones continuously sample for, and respond to, guidance information provided by cell surfaces and the extracellular matrix. To identify specific guidance cues, growth cones have sensor molecules on their surface, which are expressed differentially during the temporospatial progress of axon outgrowth, at levels that depend on the pattern of neural activity. However, it has not been elucidated whether a change in gene expression can indeed change the molecular composition and, hence, the function of the sensor apparatus of growth cones. RESULTS: We have constructed adenoviral gene transfer vectors of the chicken growth cone sensor molecules axonin-1 and Ng-CAM. Using these vectors, we initiated the expression of axonin-1 and Ng-CAM in rat dorsal root ganglia explants during ongoing neurite outgrowth. Using specific surface immunodetection at varying time points after infection, we found that axonin-1 and Ng-CAM are transported directly to the growth cone and inserted exclusively in the growth cone membrane and not in the axolemma of the axon shaft. Furthermore, we found that axonin-1 and Ng-CAM do not diffuse retrogradely, suggesting that the sensor molecules are integrated into multimolecular complexes in the growth cone. CONCLUSIONS: During axon outgrowth, the pathway sensor apparatus of the growth cone is continuously updated by newly synthesized sensor molecules that originate directly from the transcription/translation machinery. Changes in the expression of sensor molecules may have a direct impact, therefore, on the exploratory function of the growth cone.

Animals↗
PubMed1996

Functional analysis of opioid receptor subtypes in the ventromedial hypothalamic nucleus of the rat.

Effects of [Met5]enkephalin and agonists selective for mu-, delta- and kappa-opioid receptors were tested in vitro on neurons of the hypothalamic ventromedial nucleus of ovariectomized, estrogen-primed rats. Brain slices were perfused with artificial cerebrospinal fluid and opioid drugs were applied by bolus injection into the perfusion line. Single unit activity was recorded extracellularly. The majority of ventromedial hypothalamic nucleus neurons tested exhibited marked inhibitory responses to [Met5]enkephalin. The inhibition was blocked by naloxone, by the selective delta-opioid receptor antagonist naltrindole and, to a lesser extent, by the mu-opioid receptor antagonist beta-funaltrexamine. The kappa-opioid receptor antagonist nor-binalmorphimine had virtually no effect on [Met5]enkephalin inhibition. Agonists selective for delta-([D-Pen2,D-Pen5]enkephalin, DPDPE) and for mu-([D-Ala2,MePhe4,Gly-ol5]enkephalin, DAGO) opioid receptors also potently inhibited the ventromedial hypothalamic nucleus neurons while the kappa-opioid receptors agonist U50,488 only produced a small inhibition in a smaller number of units. These results provide functional evidence that [Met5]enkephalin, a potential opioid transmitter in the ventromedial hypothalamic nucleus, can exert an inhibitory effect by acting on delta-and mu-opioid receptors.

Action Potentials↗
PubMed1996

Migration of luteinizing hormone-releasing hormone (LHRH) neurons in early human embryos.

Luteinizing hormone-releasing hormone (LHRH) neurons originate in the epithelium of the medial olfactory pit and migrate from the nose into the forebrain along nerve fibers rich in neural cell adhesion molecule (N-CAM). The present study examined the ontogenesis of LHRH neurons in early human embryos and found a similar pattern of development of these cells. Luteinizing hormone-releasing hormone immunoreactivity was detected in the epithelium of the medial olfactory pit and in cells associated with the terminal-vomeronasal nerves at 42 (but not 28-32) days of gestation. The migration route of these cells was examined with antibodies to N-CAM and antibodies to polysialic acid (PSA-N-CAM), which is present on N-CAM at certain stages of development. Neural cell adhesion molecule immunoreactivity was present in a population of cells in the olfactory placode of the earliest embryos examined (28-32 days) and later (42 and 46 days) throughout the migration route. The PSA-N-CAM immunoreactivity was not detected until 42 days and was present in a more limited distribution in nerve fibers streaming from the olfactory placode and along the caudal part of the migration route below the forebrain. Previous studies have indicated that the highly sialated form of N-CAM is less adhesive. The PSA-N-CAM may therefore facilitate the migration of these cells by lessening the adhesion between the fascicles that make up the migration route, expediting the passage of cords of LHRH cells between the nerve fibers as these cells move toward the brain.

Antibodies, Monoclonal↗
PubMed1996

Effects of testosterone and 7 alpha-methyl-19-nortestosterone (MENT) on sexual and aggressive behaviors in two inbred strains of male mice.

Behavioral and endocrine effects of a synthetic androgen, 7 alpha-methyl-19-nortestosterone (MENT), which is not 5 alpha-reduced to dihydrotestosterone, were compared to those of testosterone in two inbred strains of male mice, C57BL/6J and DBA/2J, in two experiments. In the first experiment, seminal vesicle (SV) weights, kidney weights, and circulating steroid levels were examined in castrated mice treated with three doses of testosterone (3.125, 12.5, or 50 micrograms/day) or four doses of MENT (1, 4, 16, or 64 micrograms/day) for 2 weeks to determine the optimal replacement levels of the two androgens for behavioral studies. Both testosterone and MENT dose-dependently increased the SV weights that were greatly reduced, in both strains, by castration. MENT was more effective than testosterone in increasing SV weights, fully restoring them to intact levels in both strains, at the dose of 4 micrograms/day. At the dose of 12.5 micrograms/day, testosterone restored the SV weights completely in C57BL/6J and up to 80% in DBA/2J mice. DBA/2J mice were more sensitive than C57BL/6J mice to both androgens, as measured by kidney weights, although circulating levels of either steroid were very similar between the two strains of mice. In the second experiment, we investigated the effects of testosterone (12.5 micrograms/day) and MENT (4 micrograms/day) on sexual and aggressive behaviors. In each strain, MENT-treated and testosterone-treated mice showed similar numbers of mounts or intromissions. MENT was equally effective as testosterone to fully (C57BL/6J) or partially (DBA/2J) restore sexual behaviors as well as the SV weights to the intact levels. In contrast, MENT-treated mice of both strains were much less aggressive than testosterone-treated mice. In both C57BL/6J and DBA/2J mice, testosterone fully restored aggression to the intact levels as measured by aggression latency, number of aggressive bouts, and duration of aggression, whereas aggressive behaviors of the MENT-treated groups were not different from those of the castrated control groups. These results suggest that MENT can restore both male sexual behaviors and reproductive organ weights as effectively as testosterone, at one-third of the testosterone dose, without stimulating male aggressive behaviors.

Aggression↗
PubMed1996

Reproductive functions illustrating direct and indirect effects of genes on behavior.

Effects of gene products on reproductive behavior which are relatively direct include those of the estrogen receptor and progesterone receptor. For example, work with estrogen receptor-deficient (ERKO) female mice has extended previous evidence contributing to the neurochemical analysis of lordosis behavior. On the other hand, sex differences in behavior present a classic example of indirect effects of genes on behavior. Work with ERKO male mice shows the necessity of ER gene expression for normal masculinization of the brain. In particular, behavioral assay results distinguish apparent motivational performance of ERKO males from male mating reflexes: the former is similar to that of wild-type males in important respects, while the latter are deficient in ERKO males. The present paper first reviews a small number of clear genetic contributions to reproductive behaviors, and then reports one experiment pertinent to the interpretation of the behavioral status of ERKO male mice.

Animals↗
PubMed1996

Application of antisense DNA method for the study of molecular bases of brain function and behavior.

The antisense DNA method has been used successfully not only in vitro but also with in vivo systems to block effectively the expression of specific genes. An increasing number of studies have shown that antisense DNA administered directly into the brain can modify various kinds of behaviors. These findings strongly suggest that the antisense DNA method can be widely used as a powerful tool for the study of the molecular bases of behavior. In addition to traditional methods of behavioral genetics, the antisense DNA method may provide a new approach for the study of the effects of gene in behavioral function. In this article, we review recent studies reporting in vivo effects of antisense DNA on brain function and behavior.

Animals↗
PubMed1996

Anesthesia during hormone administration abolishes the estrogen induction of preproenkephalin mRNA in ventromedial hypothalamus of female rats.

Estrogen treatment increases preproenkephalin (PPE) mRNA levels in the ventromedial nucleus of the hypothalamus (VMH). Roy et al. (Brain Res., 337 (1985) 163-166) discovered that anesthesia during estrogen priming could reduce female rat sexual receptivity. In the present study we tested whether the action of estrogen to induce PPE gene expression in the VMH could be similarly affected by anesthesia. By quantitative in situ hybridization and slot-blot analysis techniques we found a 1.8-fold increase in PPE mRNA levels in the VMH after 1 hour of estrogen treatment in ovariectomized (OVX) Sprague-Dawley female rats. Anesthetizing the rats with pentobarbital for 1 h during the exposure to estrogen blocked the estrogen induction of PPE mRNA in the VMH. By way of contrast no changes in the PPE mRNA levels were observed in the caudate putamen. A similar trend was seen using chloral hydrate. It appears that neuronal activity is required for the early phase of estrogen induction of PPE mRNA levels in the VMH. This in turn could be correlated with changes in female sociosexual behaviors.

Anesthesia, General↗
PubMed1996

Estrogen regulation of gonadotropin-releasing hormone receptor messenger RNA in female rat pituitary tissue.

Gonadotropin releasing hormone (GnRH) is crucial in regulating the reproductive system of female vertebrates. In the present study we have analyzed the estrogen regulation of the GnRH receptor mRNA at the cellular level in Sprague-Dawley female rats. Northern blot analysis detected 3 species (5.0, 4.5 and 1.4 kb) of GnRH receptor mRNA in pituitary tissues. The GnRH receptor mRNA levels of these 3 species were increased by estrogen. By in situ hybridization we observed a 3.5-fold increase in GnRH receptor mRNA levels after 48 h of estrogen treatment when compared to ovariectomized (OVX) rats, 12 h of estrogen treatment did not change the GnRH mRNA levels. Similar increases in GnRH receptor mRNA levels by estrogen were also found in Wistar-Imamichi female rat pituitary tissue. In situ hybridization analysis identified clusters of anterior pituitary cells that expressed the GnRH receptor mRNA. The estradiol effect depends on increased mRNA levels in these clusters. Moreover, a significant increase in the number of pituitary cells that expressed GnRH receptor was observed after 48 h of estrogen treatment. These findings suggest that the mechanisms for estrogen regulation of GnRH receptor include changing levels of GnRH receptor mRNA in the rat pituitary.

Animals↗
PubMed1996

Thyrotropin-releasing hormone (TRH) has independent excitatory and modulatory actions on lamina IX neurons of lumbosacral spinal cord slices from adult rats.

Coronal and horizontal slices of the lumbar and sacral spinal cord, respectively, of ovariectomized adult rats, either treated with estrogen (OVX+E) or untreated (OVX), were used to test the neuronal actions of TRH and its metabolite, cyclo(His-Pro) (or cHP). Both coronal slices, which possess only short stumps of ventral roots (VRs), and horizontal slices, in which long sections of VRs were preserved, were used for extracellular recording of single motor and other types of neurons. Methodological comparisons between these two types of slices showed that the length of VRs preserved had no significant effect on the characteristics of motoneurons (MNs). In coronal slices, MNs in medial and lateral lamina IX (MNM and MNL, respectively) were identified by antidromic activation. Of these lumbar MNs, estrogen treatment lowered the antidromic activation threshold for MNM but not MNL. Because MNM innervate the back muscles crucial for the execution of the estrogen-dependent lordosis, the observed estrogen effect may contribute to the hormone's induction of the sexual behavior. The recorded MNs and other types of neurons were subjected to bath applications of TRH, cHP, and neurotransmitters. TRH was found to be capable of evoking an early, shorter-lasting neuronal excitation and/or a late, longer-lasting modulation of neuronal responses to transmitters. Each neuronal action could occur with or without the other, and the occurrence of the excitation did not affect the probability of whether a modulation would occur later. The modulatory, but not the excitatory, action appeared to be shared by cHP, because cHP could also modulate neuronal responses in similar, if not identical, ways as TRH did, but could neither stimulate neurons nor mimic TRH in desensitizing TRH-evoked excitation. The modulatory actions of the two peptides were not affected by estrogen. Although the excitatory action was desensitized by repeated TRH applications, the modulatory action did not appear to be attenuated but instead was often enhanced by repeated administrations of TRH and/or cHP. These results, together with the essentially identical findings from our previous study on hypothalamic neurons, indicate that the excitatory and the modulatory actions of TRH are independent of each other and, hence, are mediated by different subcellular mechanisms.

Animals↗