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PubMed1994

Stimulation of oxytocin release within the supraoptic nucleus and into blood by CCK-8.

Simultaneous microdialysis in brain and blood was used to monitor the effects of systemic and central cholecystokinin octapeptide (CCK-8) on the release of oxytocin and vasopressin within the hypothalamic supraoptic nucleus (SON) as well as into blood of urethan-anesthetized female rats. Administration of CCK-8 (20 micrograms/kg iv) increased oxytocin contents in 30-min microdialysates sampled simultaneously within the SON (1.8-fold) and blood (2.4-fold, both P < 0.05) compared with prestimulation levels. In another experiment, after bilateral administration of CCK-8 directly into the SON (10 ng/0.5 microliter) via a microdialysis/infusion probe, oxytocin contents in dialysates sampled from the left and right SON were increased 2.3- and 1.7-fold (P < 0.05), respectively. In simultaneously sampled dialysates from the jugular vein, oxytocin content increased 2.3-fold (P < 0.05). In contrast, oxytocin in dialysates sampled outside the hypothalamic nuclei was not altered by systemic or central CCK-8. The direct infusion of CCK-8 into both SON increased the release of vasopressin within the SON 1.7-fold (P < 0.05) but failed to significantly change vasopressin release into blood. The present findings show a coordinated regulation of intranuclear and systemic release of oxytocin in response to systemic and central CCK-8 and provide further evidence for a possible involvement of endogenous oxytocin in the complex regulation of ingestive and reproductive behaviors induced by CCK-8 at the brain level.

Animals↗
PubMed2006

A store-operated Ca(2+) influx pathway in the bag cell neurons of Aplysia.

Although store-operated Ca(2+) influx has been well-studied in nonneuronal cells, an understanding of its nature in neurons remains poor. In the bag cell neurons of Aplysia californica, prior work has suggested that a Ca(2+) entry pathway can be activated by Ca(2+) store depletion. Using fura-based imaging of intracellular Ca(2+) in cultured bag cell neurons, we now characterize this pathway as store-operated Ca(2+) influx. In the absence of extracellular Ca(2+), the endoplasmic reticulum Ca(2+)-ATPase inhibitors, cyclopiazonic acid (CPA) or thapsigargin, depleted intracellular stores and elevated intracellular free Ca(2+). With the subsequent addition of extracellular Ca(2+), a prominent Ca(2+) influx was observed. The ryanodine receptor agonist, chloroethylphenol (CEP), also increased intracellular Ca(2+) but did not initiate store-operated Ca(2+) influx, despite overlap between CEP- and CPA-sensitive stores. Bafilomycin A, a vesicular H(+)-ATPase inhibitor, liberated intracellular Ca(2+) from acidic stores and attenuated subsequent Ca(2+) influx, presumably by replenishing CPA-depleted stores. Store-operated Ca(2+) influx was partially blocked by low concentrations of La(3+) or BTP2, and strongly inhibited by either 1-[b-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole (SKF-96365) or a high concentration of Ni(2+). Regarding IP(3) receptor blockers, 2-aminoethyldiphenyl borate, but not xestospongin C, prevented store-operated Ca(2+) influx. However, jasplakinolide, an actin stabilizer reported to inhibit this pathway in smooth muscle cell lines, was ineffective. The bag cell neurons initiate reproductive behavior through a prolonged afterdischarge associated with intracellular Ca(2+) release and neuropeptide secretion. Store-operated Ca(2+) influx may serve to replenish stores depleted during the afterdischarge or participate in the release of peptide that triggers behavior.

Anilides↗
PubMed1979

Identifiable neurons controlling penile eversion in the leech.

1. This paper describes the neuroanatomy and electrophysiology of motor neurons causing penile eversion in the leech. 2. The male organ is innervated by ganglia 5 and 6 of the 34 ganglia in the leech brain through special sex nerves deriving from anterior roots. These sex ganglia have at least 200 more neurons than the other midbody ganglia. Many of the extra neurons are involved in reproductive behavior. 3. Two pairs of motor neurons on the ventral side of ganglion 6, named rostral and lateral neurons, are the only ones that elicit full penile eversion. Evidence that the lateral and rostral neurons are, in fact, motor neurons comes from HRP and electrophysiological studies. HRP injections reveal that each neuron's single primary axon grows into the sex nerve. Electrophysiological evidence is twofold: a) action potentials of lateral and rostral cells can still contract the genitalia after the neurons are deafferented from chemical synaptic input in the ganglion by high Mg2+, b) their action potentials are followed by junction potentials in male organ muscle fibers.

Animals↗
PubMed1993

The peptide FMRFa terminates a discharge in Aplysia bag cell neurons by modulating calcium, potassium, and chloride conductances.

1. Electrical stimulation of an afferent nerve triggers a 30-min period of firing of action potentials in the bag cell neurons of Aplysia californica. This afterdischarge causes the animal to undergo a long-lasting sequence of stereotyped reproductive behaviors culminating in laying of eggs. The connective sheath surrounding the clusters of bag cell neurons is interspersed with a network of particles that are immunoreactive to an antiserum raised against the tetrapeptide neurotransmitter Phe-Met-Arg-Phe-amide (FMRFa). Because the sheath is known to be rich in processes from the bag cell neurons, these data suggest that an FMRFa-like peptide may be located in neuronal processes that are in close contact with those of the bag cell neurons. 2. Application of FMRFa to bag cell neurons in intact abdominal ganglia effectively suppresses the onset of the afterdischarge in response to electrical stimulation and terminates an ongoing afterdischarge in a reversible manner. 3. Application of FMRFa to isolated bag cell neurons in primary cell culture causes an attenuation of the amplitude of evoked action potentials. This could be attributed in part to an attenuation of the voltage-activated calcium current, which in voltage-clamp experiments was found to be reduced by 10-40%. 4. Application of FMRFa to bag cell neuron in primary culture also causes a hyperpolarization of the membrane potential by activating an outward current with a reversal potential of approximately -67 mV. Ion substitution experiments, together with application of channel blockers, indicate that this current is carried by both potassium and chloride ions. Activation of this current is suppressed by treatment of the cells with either a cyclic AMP analogue or a phorbol ester activator of protein kinase C. 5. FMRFa exerts a powerful inhibitory influence on the bag cell neurons by altering the properties of ion currents involved in both the generation of action potentials and control of the resting potential. This suggests that this neuropeptide plays a role in the regulation of the onset of afterdischarge in vivo.

Animals↗
PubMed2000

Anabolic steroids induce region- and subunit-specific rapid modulation of GABA(A) receptor-mediated currents in the rat forebrain.

Anabolic-androgenic steroids (AAS) have become significant drugs of abuse in recent years with the highest increase reported in adolescent girls. In spite of the increased use of AAS, the CNS effects of these steroids are poorly understood. We report that in prepubertal female rats, three commonly abused AAS, 17alpha-methyltestosterone, stanozolol, and nandrolone, induced rapid and reversible modulation of GABAergic currents in neurons of two brain regions known to be critical for the expression of reproductive behaviors: the ventromedial nucleus of the hypothalamus (VMN) and the medial preoptic area (mPOA). All three AAS significantly enhanced peak synaptic current amplitudes and prolonged synaptic current decays in neurons of the VMN. Conversely all three AAS significantly diminished peak current amplitudes of synaptic currents from neurons of the mPOA. The endogenous neuroactive steroids, 3alpha-hydroxy-5alpha-pregnan-20-one and 5alpha-androstane-3alpha,17beta-diol, potentiated currents in the VMN as did the AAS. In contrast to the negative modulation induced by AAS in the mPOA, the endogenous steroids potentiated responses in this region. To determine the concentration response relationships, modulation by the AAS, 17alpha-methyltestosterone (17alpha-meT), was assessed for currents evoked by ultrafast perfusion of brief pulses of GABA to acutely isolated neurons. Half-maximal effects on currents elicited by 1 mM GABA were elicited by submicromolar concentrations of AAS for neurons from both brain regions. In addition, the efficacy of 10(-5) to 10(-2) M GABA was significantly increased by 1 microM 17alpha-meT. Previous studies have demonstrated a striking dichotomy in receptor composition between the VMN and the mPOA with regard to gamma subunit expression. To determine if the preferential expression of gamma(2) subunit-containing receptors in the VMN and of gamma(1) subunit-containing receptors in the mPOA could account for the region-specific effects of AAS in the two regions, responses elicited by ultrafast perfusion of GABA to human embryonic kidney 293 cells transfected with alpha(2), beta(3), and gamma(2) or alpha(2), beta(3), and gamma(1) subunit cDNAs were analyzed. As with native VMN neurons, positive modulation of GABA responses was elicited for alpha(2)beta(3)gamma(2) recombinant receptors, while negative modulation was induced at alpha(2)beta(3)gamma(1) receptors as in the mPOA. Our data demonstrate that AAS in doses believed to occur in steroid abusers can induce significant modulation of GABAergic transmission in brain regions essential for neuroendocrine function. In addition, the effects of these steroids can vary significantly between brain regions in a manner that appears to depend on the subunit composition of GABA(A) receptors expressed.

Anabolic Agents↗
PubMed2002

Estrogen and thyroid hormone receptor interactions: physiological flexibility by molecular specificity.

The influence of thyroid hormone on estrogen actions has been demonstrated both in vivo and in vitro. In transient transfection assays, the effects of liganded thyroid hormone receptors (TR) on transcriptional facilitation by estrogens bound to estrogen receptors (ER) display specificity according to the following: 1) ER isoform, 2) TR isoform, 3) the promoter through which transcriptional facilitation occurs, and 4) cell type. Some of these molecular phenomena may be related to thyroid hormone signaling of seasonal limitations upon reproduction. The various combinations of these molecular interactions provide multiple and flexible opportunities for relations between two major hormonal systems important for neuroendocrine feedbacks and reproductive behaviors.

Animals↗
PubMed2005

Endometrial cancer incidence trends in Europe: underlying determinants and prospects for prevention.

More than one in 20 female cancers in Europe are of the endometrium. Surveillance of incidence rates is imperative given the rapidly changing profile in the prevalence and distribution of the underlying determinants. This study presents an analysis of observed and age-period-cohort-modeled trends in 13 European countries. There were increasing trends among postmenopausal women in many Northern and Western countries. Denmark and possibly France and Switzerland were exceptions, with decreasing trends in postmenopausal women. In premenopausal and perimenopausal women, declines were observed in Northern and Western Europe, most evidently in Denmark, Sweden, and the United Kingdom, affecting consecutive generations born after 1925. These contrast with the increasing trends regardless of menopausal age in some Southern and Eastern European countries, particularly Slovakia and Slovenia. These observations provide evidence of changes in several established risk factors over time and have implications for possible primary prevention strategies. In postmenopausal women, changes in reproductive behavior and prevalence of overweight and obesity may partially account for the observed increases, as well as hormone replacement therapy use in certain countries. Combined oral contraceptive use may be responsible for the declines observed among women aged <55 years. Whereas there are some prospects for chemoprevention in premenopausal women as oral contraceptive use becomes more widespread in Europe, increases in obesity and decreases in fertility imply that endometrial cancer in postmenopausal women will become a more substantial public health problem in the future.

Adult↗
PubMed1998

Central monoamines in free-ranging lizards: differences associated with social roles and territoriality.

During the breeding season different social classes of field-active lizards, Sceloporus jarrovi, exhibit regionally specific changes in central monoaminergic activation. Changes in serotonergic content and turnover between lizards from different social classes are seen in forebrain structures (telencephalon and diencephalon) and reflect events associated with reproductive behaviors, stress and aggression. Males without territories (satellite males) exhibit higher forebrain serotonin (5-HT) system activation compared to territorial males and adult females. This serotonergic activation includes increased 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA/5-HT ratio, suggesting increased release and catabolism. Satellite males also exhibit higher 5-HIAA/5-HT ratios (serotonergic turnover) compared to territorial males following agonistic interactions. Territorial males, immediately following aggressive defense of territories against intruder males, exhibit increased 5-hydroxytryptophan (5-HTP) levels, higher 5-HIAA levels and 5-HIAA/5-HT ratio, higher epinephrine levels, greater MHPG/NE, more DOPAC and larger DOPAC/DA ratio compared to territorial males that did not have an aggressive encounter. These differences suggest activation of 5-HT, norepinephrine (NE), and dopamine (DA) systems by the synthesis and release of more 5-HT and the release of more NE and DA during aggressive defense of territory. The highest activity of serotonergic system is exhibited by satellite males compared to territorial males, perhaps reflecting stress in subordinate animals from social and ecological sources.

Aggression↗
PubMed1998

Coexistence of FMRFAMIDE-like and LHRH-like immunoreactivity in the terminal nerve and forebrain of the big brown bat, Eptesicus fuscus.

The coexistence of molluscan cardioexcitatory neuropeptide (FMRFAMIDE) and luteinizing hormone-releasing hormone (LHRH) was studied in the nervous system of the big brown bat, Eptesicus fuscus, with immunocytochemistry. Within mammals, this is the first report of the coexistence of these neuropeptides in the terminal nerve. In juvenile and adult bats, both neuropeptides are distributed identically throughout the terminal nerve (tn), and they coexist in many parts of the prosencephalon from the olfactory bulb as far caudally as the interpeduncular nucleus. Peripherally, on the basal surface of the forebrain, fibers and a few perikarya, which may belong to the tn, form a loose plexus. Within the brain wall, regions of maximal immunoreactivity (ir) are the habenula, medial preoptic area, arcuate nucleus, and the infundibulum. Whereas in most areas of the prosencephalon (e.g., stria terminalis and bed nuclei, amygdaloid complex) fibers show stronger immunoreactivity to FMRFAMIDE, labeling of fibers in the habenula and infundibulum is largely identical for both neuropeptides. The arcuate nucleus contains a large number of perikarya and is the major source of both FMRFAMIDE- and LHRH-ir within the forebrain. A number of fibers run along the ependyma of the ventricular system and seem to terminate here; this is particularly evident in the median eminence and infundibular stalk. In the big brown bat, there seems to exist a continuum of FMRFAMIDE- and LHRH-ir throughout the tn and those structures of the forebrain that are known to be engaged in the control of mating behavior, reproduction, and rhythmicity. Concerning the hypothalamo-hypophyseal-gonadal axis, the arcuate nucleus may serve as a central hub between the olfactory/terminal input and superior areas including the limbic system. In contrast to LHRH immunoreactivity, FMRFAMIDE-like ir extends throughout the brainstem and cervical spinal cord. This system may also be involved in the processing and modulation of autonomic input via the parabrachial and solitary nuclei, the rhombencephalic central gray, and its projection into the hypothalamus (paraventricular nucleus), thus facilitating feed-back of gonadotropic influences of the terminal nerve and prosencephalon.

Animals↗
PubMed1998

The peptide orphanin FQ inhibits beta-endorphin neurons and neurosecretory cells in the hypothalamic arcuate nucleus by activating an inwardly-rectifying K+ conductance.

Orphanin FQ (OFQ) is a novel heptadecapeptide whose structure resembles that of dynorphin A1-17. Its receptor shares appreciable homology with mu-, delta- and kappa-opioid receptors, and is highly expressed in the hypothalamus. The present study examined the effects of OFQ on neurons within the arcuate nucleus (ARC) of the mediobasal hypothalamus, using intracellular recordings from coronal slices. In current clamp, OFQ produced a hyperpolarization of ARC neurons, including those immunopositive for beta-endorphin, tyrosine hydroxylase and gonadotropin-releasing hormone. This hyperpolarization was dose-dependent, insensitive to antagonism by naloxone and was associated with a decrease in input resistance. In voltage clamp, OFQ produced an outward current associated with an increase in conductance. Varying the extracellular K+ concentration shifted the reversal potential for the OFQ response to the degree predicted by the Nernst equation. Furthermore, barium chloride markedly attenuated both the OFQ-induced hyperpolarization and decrease in input resistance. Administration of maximally effective concentrations of OFQ, followed by coadministration of maximal concentrations of either OFQ and the mu-opioid receptor agonist DAMGO or OFQ and the GABAB receptor agonist baclofen produced additive hyperpolarizations and outward currents. If DAMGO was applied first, followed by the coadministration of DAMGO and OFQ, then the responses were occluded. Taken together, these results indicate that OFQ inhibits beta-endorphin neurons, as well as A12 dopamine and GnRH neurosecretory cells, within the ARC by activating a subset of inwardly-rectifying K+ channels. This suggests that OFQ is not only an antiopioid peptide, but that it also modulates the hypothalamo-pituitary axis and, ultimately, reproductive behavior.

Animals↗
PubMed2004

Oxytocin and vasopressin immunoreactivity within the forebrain and limbic-related areas in the mustached bat, Pteronotus parnellii.

The nonapeptides, oxytocin and arginine vasopressin, play an important role in mammalian social and reproductive behavior. Using immunocytochemical procedures, we identified oxytocin-immunoreactive neurons in the frontal and auditory cortices, limbic areas such as the medial septal nucleus, horizontal limb of the diagonal band and the amygdala. Only arginine vasopressin neurons were present in the bed nucleus of the stria terminalis. In limbic-related areas, the hypothalamic paraventricular and supraoptic nuclei and the nucleus centralis contained both oxytocin and arginine vasopressin neurons. The medial preoptic area showed a positive reaction for several arginine vasopressin fibers, but not oxytocin fibers, except in one female bat sacrificed during the breeding season. Arginine vasopressin fibers were observed in another limbic-related area, the periaqueductal gray. Furthermore, oxytocin was predominantly localized within sensory (e.g., auditory) and frontal cortex and limbic areas, whereas arginine vasopressin was restricted largely to known audiovocal regions of the periaqueductal gray. Classical neurosecretory nuclei in the hypothalamus contain both peptides. Oxytocin-immunoreactive neurons were also found in other structures such as the olfactory bulb, olfactory tubercle, primary and secondary motor cortex, fronto-parietal cortex, piriform cortex and the nucleus of the internal capsule. Both oxytocin and arginine vasopressin immunoreactivity was present in the suprachiasmatic nucleus, median eminence, neural lobe of the hypophysis and the pineal gland. Together with previous studies, the presence of these peptides within auditory areas of the cortex (sensory and frontal), and limbic as well as limbic-related regions provides anatomical evidence supporting their proposed role in social vocal behaviors and probably in auditory processing.

Animals↗
PubMed2004

Social signals regulate gonadotropin-releasing hormone neurons in the green treefrog.

Animals coordinate their physiological state with external cues to appropriately time reproduction. These external cues exert effects through influences on the gonadotropin-releasing hormone neurons (GnRH), at the apex of the hypothalamus-pituitary-gonad (HPG) axis. In green treefrogs, mating calls are important regulators of reproductive behavior and physiology. Reception of mating calls causes an increase in androgen levels, and androgens promote the production of mating calls, demonstrating a mutual influence between the communication and endocrine systems. In order to investigate the central nervous system correlates of social regulation of the HPG axis in green treefrogs, we exposed males to a mating chorus or a control stimulus (tones), counted the resulting number of septo-preoptic GnRH-immunoreactive cells (GnRH-ir), and measured changes in plasma androgens. We found that reception of the mating chorus caused an increase in the number of GnRH-ir cells. As previously shown, we also found that the reception of the mating chorus resulted in higher androgen levels, suggesting that the higher GnRH-ir cell number represents increased GnRH production and release. We suggest that mating calls are an important supplementary cue that promotes GnRH production and release within the context of GnRH regulation by seasonal cues. Previous studies have proposed a neuroanatomical link between the anuran auditory system and GnRH neurons. Our results demonstrate a functional role for this proposed sensory-endocrine circuit, and show for the first time an influence of acoustic signals on GnRH neurons.

Acoustic Stimulation↗
PubMed1997

Evolution of vertebrate olfactory systems.

The general features of the olfactory system are remarkably consistent across vertebrates. A phylogenetic analysis of central olfactory projections indicates that at least three distinct olfactory subsystems may be broadly present in vertebrates and that a fourth, the accessory olfactory or vomeronasal system, arose in tetrapods. The origin and function of the vomeronasal system have been the subject of much controversy, but some conclusions can be drawn. The vomeronasal system did not arise as an adaptation to terrestrial life, as indicated by the presence of a vomeronasal system in modern aquatic amphibians and the increasing paleontological evidence that the last common ancestor of amphibians and amniotes was aquatic. The vomeronasal system is involved in both foraging and reproductive behaviors in reptiles and has been shown to be involved in some pheromonally mediated behaviors in mammals. However, among mammals, some pheromonal responses are not mediated by the vomeronasal system, and the possible involvement of the vomeronasal system in other type of behaviors has not yet been investigated. Thus, the relative functions of the olfactory and vomeronasal systems of tetrapods remain unclear. Other hypotheses that features of the olfactory system are specialized for aquatic chemoreception or for pheromone detection are similarly insupportable. For example, the suggestion that members of the olfactory receptor family can be separated into two groups that function for transduction of air-borne or water-borne odorants is contradicted by the presence of both groups in aquatic amphibians and by a phylogenetic analysis of the sequences for these genes. Interestingly, the putative odorant receptors from the vomeronasal epithelium share little sequence similarity with those from the olfactory epithelium, indicating that these receptors may have been independently co-opted from the larger family of seven transmembrane domain receptors for use in odor transduction. A phylogenetic analysis of the distribution of olfactory receptor cell types indicates that microvillar olfactory receptor cells are widespread among vertebrates and are not restricted to aquatic animals or to the vomeronasal epithelium of tetrapods. Previous suggestions that all microvillar receptor cells are specialized for the detection of pheromones are not tenable. Attempts to recognize features of the olfactory system that are common to all vertebrates and might be specialized for the detection of pheromones vs. more general odorants, or for the detection of water-borne vs. air-borne odorants, are not supported by current evidence.

Animals↗
PubMed1991

Thalamic and midbrain auditory projections to the preoptic area and ventral hypothalamus in the green treefrog (Hyla cinerea).

Iontophoretic injections of horseradish peroxidase (HRP) into either the preoptic area or ventral hypothalamus of the green treefrog, (Hyla cinerea), demonstrated inputs from thalamic and midbrain auditory nuclei. In a pattern similar to that seen in Rana catesbeiana and Rana pipiens, the central thalamic and secondary isthmal nuclei were found to provide heavy input to the ventral hypothalamus. Additionally, a lighter input from the anterior thalamic nucleus was seen. In contrast, the preoptic area receives a major input from the anterior thalamic and secondary isthmal nuclei, and possibly a sparse input from the central thalamic nucleus. These results suggest that in treefrogs multimodal and auditory information may reach the preoptic area and ventral hypothalamus, two regions involved in endocrine regulation and the control of reproductive behavior, via largely separate major pathways from the thalamus combined with a common midbrain input. Furthermore, the ventral hypothalamus receives heavy input from the preoptic area, lateral amygdala, suprachiasmatic nucleus, anterior entopeduncular nucleus, and a lighter input from the striatum. Nonauditory afferents to the preoptic area originate in the medial and lateral septal nuclei, medial pallium, and the dorsal-, lateral-, and ventral hypothalamus. The preoptic area and ventral hypothalamus are reciprocally connected.

Animals↗
PubMed1989

Regulation of high-affinity GABAa receptors in specific brain regions by ovarian hormones.

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 autoradiography. Treatment of ovariectomized and adrenalectomized female rats with E resulted in a decrease of muscimol binding only in specific estrogen-sensitive brain regions like the ventromedial nuclei (VMN) of the hypothalamus, the arcuate nucleus (ARC), the medial amygdala and the midbrain central grey (MCG). When administered alone, P had no effect. However, in estrogen-primed females, P increased muscimol binding in both VMN and MCG to levels seen in control animals. Thus, E and P exert opposite effects on the GABAa receptor within these two nuclei. As both hormones facilitate female reproductive behavior as well as the release of luteinizing hormone, present results suggest that E and P affect muscimol binding by different mechanisms.

Adrenalectomy↗
PubMed1991

Sex difference in estradiol regulation of progestin receptor mRNA in rat mediobasal hypothalamus as demonstrated by in situ hybridization.

Previous studies have shown that estrogen increases the level of progestin receptors (PR) to a greater extent in female than in male rat hypothalamus. In order to determine if sex-specific regulation of the PR protein might be attributable to estrogenic effects on the PR message, in situ hybridization was used to assess sex differences in levels of estrogen-inducible PR mRNA in specific brain nuclei. Here, we report a sexually differentiated pattern of estrogen-regulated PR gene expression. In female hypothalamus, estrogen administered to gonadectomized rats induced a 3.6- and a 3.3-fold increase in PR mRNA in the ventrolateral aspect of the ventromedial nucleus and arcuate nucleus, respectively, but failed to alter the level of PR mRNA in the same neuronal groups of the male. Hormone treatment did not affect the levels of PR mRNA in the dorsomedial or medial amygdaloid nuclei of either sex. These results lead towards a molecular explanation of sex differences in female reproductive behavior by revealing an estrogen-dependent up-regulation of the message for PR, a transcription factor, in a region- and sex-specific fashion.

Amygdala↗
PubMed1991

Electrophysiological actions of oxytocin on hypothalamic neurons in vitro: neuropharmacological characterization and effects of ovarian steroids.

Oxytocin (OT) neurotransmission in the brain has a facilitatory effect on sexual receptivity in rats. This effect of OT is dependent on priming by ovarian steroids, estrogen and progesterone. These steroids modulate OT binding in specific brain nuclei, including the ventrolateral portion of the ventromedial hypothalamic nucleus (vlVMN). In the present study, single-unit activity was recorded from the vlVMN in hypothalamic slices to characterize the electrophysiological actions of OT. To examine the effects of ovarian steroids on OT actions, we used brain slices prepared from ovariectomized rats either treated with estrogen or not, and some slices were treated with progesterone in vitro. OT had little modulatory action on neuronal responses to other agents, but affected the activity of large numbers of vlVMN units. Of those neurons affected, 94% responded with excitation. This predominant stimulatory action of OT is consistent with its lordosis-facilitating effect, because increases in the activity of VMN neurons are generally associated with the facilitation of lordosis. Pharmacological analyses with selective OT agonists and antagonists as well as structurally related peptides showed that the excitatory action of OT is mediated by OT receptors. Estradiol modulated several aspects of OT transmission. First, it increased neuronal responsiveness to OT, especially at the lowest concentration used (0.2 nM). In addition, it caused neuronal responses to OT to correlate significantly with responses to acetylcholine and norepinephrine, which also can act on the ventromedial hypothalamus to facilitate lordosis. Finally, estradiol enhanced the excitability of laterally projecting neurons, which have been implicated in lordosis. In estrogen-pretreated slices, addition of progesterone in vitro caused little further effect on responses of individual neurons to exogenous OT. Altogether, the present electrophysiological findings are consistent with the hypothesis that estrogen potentiates OT action by increasing functional OT receptors preferentially in lordosis-relevant neurons, thereby enabling OT to efficiently facilitate female reproductive behavior.

Acetylcholine↗
PubMed1992

Dynamic patterns of medial preoptic mu-opiate receptor regulation by gonadal steroid hormones.

The density of mu-opiate receptors located in the medial preoptic area (MPOA) of the rat hypothalamus is cyclical and sexually dimorphic. The hormonal regulation of MPOA mu-receptors was examined in ovariectomized rats treated with a variety of hormone regimens. In experiment 1, animals received acute estradiol (E2), progesterone (P), or prolactin (PRL), or E2 followed in 48 h by either P or vehicle by subcutaneous injection. Brains were removed 3 h after the final injection. In experiment 2, animals were implanted with empty or E2-filled Silastic capsules, and received either P or vehicle by injection 48 h later, at which time E2 capsules were removed. One group received E2 implants which remained in place following sham removal surgery. Brains and trunk blood for radioimmunoassay of E2 and P were collected 3, 27 or 51 h after the final injection. Frozen brain sections were prepared, incubated in [3H]D-Ala2,MePhe4,Gly-ol5-enkephalin, which selectively labels mu-receptors, and analyzed using quantitative receptor autoradiography. P treatment significantly increased MPOA mu-receptors, but only 27 h after E2 priming. Neither shorter P exposure, nor E2, P or PRL alone affected MPOA mu-receptor density. Following this delayed E2,P-induced increase, mu-receptor density subsequently decreased in the presence of absence of E2. The results suggest that E2,P treatment produces a gradual and transient increase of MPOA mu-receptor density. The subsequent decrease of receptor density is independent of the presence of E2 and may be related to receptor turnover. The time course of this effect is consistent with that of the estrus cycle. Such hormone-induced regulation of MPOA mu-receptor density could influence the physiologic effects of opiates on gonadotropin secretion and reproductive behavior in cycling females.

Animals↗