Preoptic Area Septum Research Articles

Cells Expressing RFamide-Related Peptide-1/3, the Mammalian Gonadotropin-Inhibitory Hormone Orthologs, Are Not Hypophysiotropic Neuroendocrine Neurons in the Rat

An RFamide peptide named gonadotropin-inhibitory hormone, which directly inhibits gonadotropin synthesis and secretion from the anterior pituitary gland, has recently been discovered in the avian hypothalamus. It is not known whether the mammalian orthologs of gonadotropin-inhibitory hormone and RFamide-related peptide (RFRP)-1 and -3 act in the same way. We used a newly generated antibody against the rat RFRP precursor combined with retrograde tract tracing to characterize the cell body distribution and fiber projections of RFRP-1 and -3 neurons in rats. RFRP-1/3-immunoreactive cell bodies were found exclusively within the dorsomedial hypothalamus. Immunoreactive fibers were observed in the septal-preoptic area, hypothalamus, midbrain, brainstem, and hippocampus but not in the external zone of the median eminence. Intraperitoneal injection of the retrograde tracer Fluoro-Gold in rats resulted in the labeling of the majority of GnRH neurons but essentially no RFRP-1/3 neurons. In contrast, intracerebral injections of Fluoro-Gold into the rostral preoptic area and CA2/CA3 hippocampus resulted in the labeling of 75 +/- 5% and 21 +/- 8% of RFRP-1/3 cell bodies, respectively. To assess actions at the pituitary in vivo, RFRP-3 was administered as an iv bolus to ovariectomized rats and plasma LH concentration measured at 0, 2.5, 5, 10, and 30 min. RFRP-3 had no effects on basal secretion, but GnRH-stimulated LH release was reduced by about 25% at 5 min. Together these observations suggest that RFRP-3 is not a hypophysiotropic neuroendocrine hormone in rats.

Changes in immunoreactivity to anti-cGnRH-I and -II are associated with photostimulated sexual status in male quail.

In sexually active males exposed to long-day (LD) photoperiod, perikarya in the olfactory bulb, lobus parolfactorius, n. accumbens, and preoptic region were immunoreactive (ir) to an antiserum against gonadotropin-releasing hormone (anti-cGnRH-I), and a cluster of ir-perikarya was found in the caudal-most septal area. Ir-perikarya in these brain areas of sexually inactive short-day (SD) males were located within more discrete areas than those in LD brain, which were more scattered in appearance. Absolute cell numbers were similar between LD and SD brains. Ir-fibers in LD brains were mostly in the external median eminence, along the lateral ventricle to septum (especially in and about the n. accumbens), in the septal-preoptic area, along the third ventricle, and at the n. commissure palli. There were fewer ir-fibers in SD brain. Many small dark ring-like ir-structures were found in the hyperstriatum, hippocampus, and n. taeniae. Interpreted as being ir-terminals on non-ir perikarya, these were not observed in SD males. cGnRH-II ir-perikarya were observed in only two areas regardless of reproductive status: (1) ventral to the substantia grisea centralis and caudal to the oculomotor complex, and (2) scattered in and about the lateral hypothalamus. Ir-fibers occurred in the habenular area, hyperstriatum, hippocampus, parahippocampal area, cortex piriformis, and n. taeniae. cGnRH-II ir-fibers occurred in the external median eminence but were less intensely stained than cGnRH-I ir-fibers. These fibers in SD males were similar except in the diencephalon, where scattered swellings were observed. Thus, the appearance and distribution of anti-cGnRH-I and -II ir-structures change with the sexual status of male quail, but changes in immunoreactivity to anti-cGnRH-I appear to be more widespread.

Confocal laser scanning and electron-microscopic analyses of the relationship between VIP-like and GnRH-like-immunoreactive neurons in the lateral septal-preoptic area of the pigeon.

The lateral septum and the preoptic area of birds comprise neurons immunoreactive (ir) for vasoactive intestinal polypeptide (VIP) and gonadotropin-releasing hormone (GnRH). By use of immunohistochemical single- and double-labeling techniques, we have investigated the distribution and the connections of these two types of peptidergic neurons in the lateral septal-preoptic area of the pigeon at both the light- and electron-microscopic levels. An accumulation of VIP-like-ir neurons, some of which are cerebrospinal fluid-contacting neurons, is found in the area adjacent to the ventromedial walls of the lateral ventricles in the lateral septum corresponding to the medial part of the lateral septal organ. VIP-like-ir terminals are scattered throughout the lateral septal-preoptic area, which also contains GnRH-like-ir cell bodies. The number of GnRH-like-ir cell bodies in the lateral septum is smaller than that of the VIP-like-ir neurons. GnRH-like-ir cells have a simple bipolar or multipolar shape and a beaded axon that emerges from the soma or one of the proximal dendrites. Confocal laser scanning microscopy has shown VIP-like-ir terminals in close apposition to GnRH-like-ir cell bodies in the lateral septal-preoptic area. Furthermore, the electron-microscopic double-immunolabeling has revealed synaptic contacts between VIP-like-ir axon terminals and GnRH-like-ir cell bodies or dendrites. These contacts, however, do not show synaptic specializations. The present results suggest that functional interactions take place between VIP and GnRH neurons in the lateral septal-preoptic area of the pigeon and that these interactions are involved in mediating photoperiodic responses.

Subpopulations of migrating neurons express different levels of LHRH in quail and chick embryos

LHRH neurons of the septal-preoptic area originate in the olfactory placode and migrate in the olfactory nerve into the brain during embryonic development. In adult birds, LHRH neurons have been found in the septal-preoptic area, mesencephalon and more recently in the lateral anterior nucleus of the thalamus (LA). LHRH neurons of the LA do not originate in the olfactory placode. Using immunocytochemistry, we examined the distribution of LHRH neurons in the embryonic and adult quail nervous system. The pattern of LHRH immunostaining in quail embryos was similar to that seen in chick embryos. However, there were many fewer neurons immunostained for LHRH from the olfactory placode to the septal-preoptic area in quail than in chick embryos. In contrast, there were more labeled neurons and more intense LHRH immunostaining in the thalamus of the quail than in the thalamus of chick embryos. In agreement with other studies, our data suggest that there are species differences in LHRH expression in migrating neurons. The current results should also be considered for quail-chick chimeras involving the olfactory placode.

Tangential migration of luteinizing hormone-releasing hormone (LHRH) neurons in the medial telencephalon in association with transient axons extending from the olfactory nerve

During embryonic development, luteinizing hormone-releasing hormone (LHRH) neurons migrate to the brain from the medial olfactory epithelium through the olfactory nerve. LHRH neurons enter the brain and migrate tangentially along the medial edge of the telencephalon in close association with a neural cell adhesion molecule (N-CAM) enriched fiber bundle. In the current work we wished to determine whether this N-CAM enriched 'fiber bundle is an extension of the olfactory nerve. Ablation experiments, immunocytochemistry and diI implants all suggest that LHRH neurons migrate in association with a very small subset of transient N-CAM enriched neuronal processes which, extend out of the olfactory nerve proper to the septal-preoptic area.

LHRH Neuronal Subtypes Have Multiple Origins in Chickens

Previous studies indicate that LHRH neurons of the septal-preoptic area originate in the olfactory epithelium. In the current study, we found that LHRH neurons entering the telencephalon from the olfactory nerve were not continuous with LHRH neurons in the thalamus. In addition, ablation of the olfactory placode eliminated LHRH neurons in the telencephalon but did not eliminate LHRH neurons in the thalamus. We propose that there are at least two sites of LHRH neuron production, the olfactory epithelium and the diencephalon.

Increase in number of LHRH neurones in septal-preoptic area of rats following chronic amitriptyline treatment: implication in antidepressant effect

Recent studies have implicated the peptide LHRH in a variety of actions including a role in modulation of affective behavior. The present study has been undertaken to determine its involvement in the action of antidepressants, if any, using amitriptyline (AMT) as the model antidepressant drug. The repeated administration of AMT (10 mg/kg/day) in rats increased the number of LHRH neurones in the septal-preoptic area. While 1 week of AMT treatment slightly augmented the number of LHRH neurones, the rise was not statistically significant, however, following 2 weeks of AMT treatment, a significant ( P < 0.05) increase (41.05%) was observed. Three and four weeks of AMT treatment further increased the number of neurones by 60.84% and 72.96% respectively; a remarkable rise in the LHRH immunoreactivity around organum vasculosum of lamina terminalis (OVLT) was also noticed. Acute AMT treatment had no effect on the number of neurons; however, the intensity of immunoreaction in the OVLT was slightly decreased. In the behavior despair test, a single dose of AMT displayed an immobility reducing effect which was also shown by a single dose of LHRH (1 mg/kg). The combination of LHRH (1 mg/kg) and AMT also reduced the immobility; the effect was the same as one produced by each drug given separately The results suggest that chronic AMT treatment may induce transcription and translation in LHRH cells and that the peptide LHRH may be involved in the mediation of the antidepressant effect, characteristic of AMT.

Maturation of the hypothalamo-pituitary-gonadal axis of male Syrian hamsters.

Light-microscope immunocytochemistry (ICC) was used to investigate postnatal changes in the morphology of LHRH neurons in the brains of male Syrian hamsters and to relate these changes to more overt maturational developments within the hypothalamo-pituitary-gonadal axis. The animals were maintained under long-day photoperiods (14L:10D), and groups of 6-7 were killed at 10-day intervals from Day 15 to Day 65. Their brains were fixed with 4% paraformaldehyde, sectioned sagittally with a vibratome (75 microns), and processed for ICC using monoclonal LHRH antibody HU4H. Throughout the study period, the hamsters showed a progressive increase in plasma gonadotropin levels, closely followed by an increase in testicular weight and plasma testosterone levels. Histology of the testes revealed that spermatogenesis was already qualitatively completed by Day 35 and quantitative aspects were established by Day 45. Within the brain, LHRH neuronal perikarya were distributed primarily in the medial septal-preoptic area and the diagonal band of Broca; morphologically, these immunopositive neurons were either monopolar or bipolar. The total number of LHRH neurons detected in the areas examined was approximately 440 throughout the developmental period, and the relative proportions of monopolar and bipolar subtypes (86% and 14%, respectively) remained unchanged. In contrast, the area of the perikarya, as determined by autoimage analysis, showed a highly significant age-related increase, both for the monopolar and bipolar neurons. It is suggested that these developmental changes in the LHRH neurons reflect an increase in LHRH synthesis and may, therefore, provide a neuroendocrine trigger for the onset of puberty.

Sex, nose and genotype

ANNE L. CALOF GENETICS OF DISEASE Sex, nose and genotype A candidate for the gene that is deleted in Kallmann Syndrome has been identified and encodes a protein that may be of importance in the regulation of neuronal migration. Cell migration is a fundamental process in the morpho- genesis of all tissues, It plays an especially important role in neural development, where precisely timed waves of cell migration result in the formation of the functionally specialized laminae and nuclei of the central nervous sys- tem and the ganglia of the peripheral nervous system. The luteinizing hormone-releasing hormone (LHRH) sys- tem of the brain is a particularly dramatic example of the importance of cell migration in nervous system de- velopment IEIKH-expressing neurons have recently been shown to originate in a part of the developing olfactory epithelium of the nasal cavity (the vomeronasal organ), and to migrate during fetal life from their peripheral site of origin to their ftnal destinations in two nearby regions of the brain: the septal preoptic area and the hypothala- mus [1,2] (Fig. I). LHKI-I, a hypothalamic peptide which stimulates secretion of gonadotropic hormones from the anterior pituitary, is crucial for proper development and function of the male gonad. Patients suffering from the inherited disease, Kallmann Syndrome, have two distinct defects. In the X-linked form of Kallmann Syndrome, the hypogonadism that character- izes males with this syndrome seems to be the result of gonadotropin deficiency, secondary to inadequate or in- correctly regulated searetion of IHRH. This in turn has been suggested to be due to a failure of LHRH-produc- ing neurons to migrate to their hypothalamic destination during fetal development [3]. The other major defect as- sociated with Kallmann Syndrome is anosmia, or lack of the sense of smell [ 41. Odor sensation is transmitted to the brain by sensory neurons called olfactory receptor neurons, and, like the IHRI-I neurons of the hypothala- mus, these neurons are produced by the olfactory epithe- lium of the nasal cavity. Like LHRH neurons, olfactory re- ceptor neurons also penetrate the brain, but in this case their cell bodies remain in their peripheral location, while their axons enter the brain to synapse upon neurons of the olfactory bulb. The anosmia of Kallmann Syndrome is associated with agenesis of the olfactory bulbs of the brain, and experimental embryologists have shown that proper development of the olfactory bulbs requires in- nervation by olfactory receptor neurons [5]. Thus, a fail- ure of olfactory receptor neuron axons to penetrate the brain could potentially account for the lack of olfactory bulbs in Kallmann Syndrome patients [ 31. The X-linked form of Kallmann Syndrome has been mapped to the terminal part of the short arm of the X chromosome. In one study, DNA was analysed from individuals with contiguous gene syndromes (that is, complex genetic syndromes caused by deletions of contiguous genes) resulting from deletions in Xp22.3 [6]. The Kallmann Syndrome critical interval (KilL in- terval) was assigned to the region between the break- point of an X/V translocation in a patient affected by Kallmann Syndrome and four other disorders map- ping to Xp22.3 (patient AM), and the breakpoint of an X/Y translocation in a patient unaffected by Kallmann but displaying the other disorders. A subsequent study Fig. 1. Sagittal sections through the whole hea& of developing mice, show- ing migration of LHRH-expressing neu- rons (colored purple) from the devel- oping olfactory epithelium of the nasal cavity to the brain during embryonic development. (Adapted from [Il.) Volume 2 Number 2

Identification of gonadotropin releasing hormone (GnRH) neurons projecting to the median eminence from third ventricular preoptic area grafts in hypogonadal mice

Functional gonadotropin releasing hormone (GnRH) neurosecretory activity can be restored in genetically hypogonadal ( hpg) adult mice with grafts of GnRH-containing fetal or neonatal septal-preoptic area (S/POA) tissue. Neurons implanted into the third ventricle of the host brain survive and send out axons which innervate one of the normal targets of these neurons, the median eminence (ME). Fibers terminate near primary portal vessels where GnRH is available for release into the vasculature, and this axonal outgrowth is essential for the stimulation of gonadotropin secretion, gonadal and accessory sex structure growth, gametogenesis, and fertility. Although it is known that GnRH axons reach their target, it is not known if all such neurons in a graft contribute to the projection. Taking advantage of the fact that axons in the ME, the sole host target, are outside the blood-brain barrier (BBB), long-term grafted animals were injected intraperitoneally with a retrograde tracer, Fluorogold (FG). Normal male mice were injected for comparison. Animals were sacrificed 5 days after injection and brain sections in the area of the graft were stained immunocytochemically for GnRH. In the normal male mice, two-thirds of the GnRH neurons were double-labeled with FG. In grafted individuals which slowed increased gonadal growth, the percentage of labeled cell ranged ffrom 17 to 75%. The results indicate that despite tissue injury, ectopic location, and a vastly reduced population, transplanted fetal GnRH neurons recapitulate a pattern seen in normal intact mice where some but not all neurons were capable of capturing a peripherally delivered tracer.

Origin of luteinizing hormone-releasing hormone neurons.

Neurons expressing luteinizing hormone-releasing hormone (LHRH), found in the septal-preoptic nuclei and hypothalamus, control the release of gonadotropic hormones from the anterior pituitary gland and facilitate reproductive behaviour. LHRH-expressing neurons are also found in the nervus terminalis, a cranial nerve that is a part of the accessory olfactory system and which projects directly from the nose to the septal-preoptic nuclei in the brain. During development, LHRH-immunoreactivity is detected in the peripheral parts of the nervus terminalis before it is found in the brain. Using a combination of LHRH immunocytochemistry and tritiated thymidine autoradiography in fetal mice, we show that LHRH neurons originate in the medial olfactory placode of the developing nose, migrate across the nasal septum and enter the forebrain with the nervus terminalis, arching into the septal-preoptic area and hypothalamus. Clinically, this migratory route for LHRH-expressing neurons could explain the deficiency of gonadotropins seen in 'Kallmann's syndrome' (hypogonadotropic hypogonadism with anosmia).

Dopamine-beta-hydroxylase inhibitors modulate the concentration of functional estrogen receptors in female rat hypothalamus and pituitary gland.

In order to study further the regulation of steroid hormone receptors in the brain and anterior pituitary gland of ovariectomized rats by catecholamines, the influence of two dopamine-beta-hydroxylase inhibitors on the estrogen receptor system was studied. The two inhibitors, FLA 63 and diethyldithiocarbamate (DDC) both caused a biphasic effect on the concentration of cytosol estrogen receptors in the mediobasal hypothalamus without influencing the concentration of cell nuclear estrogen receptors in the absence of estradiol; the concentration of cytosol estrogen receptors first increased and then decreased after treatment. In a study of the neuroanatomical areas in which inhibition of dopamine-beta-hydroxylase decreases the concentration of cytosol estrogen receptors, it was found that the concentration of cytosol estrogen receptors decreased after drug treatment in the mediobasal hypothalamus and preoptic area-septum, but not in the amygdala. This suggests that the decrease in concentration of hypothalamic cytosol estrogen receptors caused by dopamine-beta-hydroxylase inhibitors is not a nonspecific effect on all cytosol estrogen receptors. Finally, an injection of estradiol-17 beta in animals that had been pretreated with either DDC or FLA 63 resulted in less accumulation of cell nuclear estrogen receptors in those tissues in which the drug first caused a decrease in the concentration of cytosol estrogen receptors than in vehicle-injected controls. Therefore, under some conditions, pretreatment with a dopamine-beta-hydroxylase inhibitor decreased the concentration of functional cytosol estrogen receptors resulting in decreased nuclear estrogen receptor accumulation in response to an estradiol injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Direct, neuronal action of atrial natriuretic factor in the rat brain.

The present investigation assessed the ability of atrial natriuretic factor (ANF) to affect hypothalamic neuronal excitability. Single neurons in the rostral septal-preoptic area of the female rat brain were recorded extracellularly and tested for responsiveness to iontophoretically applied and/or pressure-ejected ANF. Neurons responsive to ANF were detected in the lateral septal nucleus, the lateral paraolfactory area, the bed nucleus of the anterior commissure, and the medial preoptic area. The majority of neurons influenced by ANF (16 out of 18) exhibited a decrease in spontaneous firing rate during application of the peptide. In some cases, the inhibitory response outlasted the period of ANF application. When both iontophoretic and pressure ejection techniques were used to apply ANF to an individual neuron, the responses were similar. The results indicate that ANF is capable of modulating the membrane excitability of rat forebrain neurons and suggest that the peptide acts as a neuromodulator/neurotransmitter within the central nervous system.

Lack of an effect of estrogen on endogenous RNA polymerase II in guinea pig brain

An early action of estrogen in peripheral target tissues is to increase endogenous RNA polymerase II activity which precedes changes in protein synthesis. Previous reports have indicated that estrogen causes a similar increase in polymerase activity in rat brain regions containing high affinity receptors for this hormone. The present series of experiments was designed to test whether a similar action of estrogen on polymerase activity occurs in guinea pig brain, with the expectation being that this enzyme might prove to be a useful marker for the early actions of estrogen. Injections of 25 or 100 μg estradiol-17β in an ethanol-saline vehicle failed to induce significant changes in polymerase II activity in the basal hypothalamus, preoptic area-septum or cortex 1, 2, 6, 13 or 24 h after hormone administration. It is concluded that the modification of RNA polymerase II activity by estrogen is not a good marker for estrogen action in the brain. This may be due to the intrinsic heterogeneity of the tissue resulting possibly in (1) increased activity in some cells and decreased activity in other cells with no net change in overall polymerase activity after estrogen treatment (2) only a small percentage of the cells responding to the steroid with altered polymerase activity with this change not detectable when whole tissue is measured or (3) only a few genes within the cells being altered in transcription by the steroid.

Adult development of the hippocampal-serotonin system of C57BL/6N mice; analysis of high-affinity uptake of 3H-5HT in slices and synaptosomes

The saturable and specific high-affinity uptake of [(3)H]serotonin ([(3)H]5HT) (5 x 10(?8) M) was studied in slices from the hippocampus, parietal cortex, septum-preoptic area, and hypothalamus of male 2, 6, 12 and 24-32 month old C57BL/6N mice. Hippocampal [(3)H]5-HT uptake showed a significant biphasic relationship to age, with lower values in the 2 and 24-32 month old mice compared to 6 month old mice. No significant age effects were seen in the other regions, or in [(3)H]norepinephrine high-affinity uptake in the hippocampus. Studies of the high-affinity uptake mechanism in synaptosomal preparations were made in a subgroup of 12 and 24 month old mice. A micro-assay using a tissue-harvester measured high-affinity uptake on 8-30 ?l of the P(2) suspension (crude-synaptosomal preparation). The high-affinity uptake was linear for 4 min at 37 degrees C and inhibited in both the adult and aged tissue by 10(?5) M cold 5-HT (83 and 78% respectively), 10(?5) M fluoxetine (85 and 82% respectively) and 10(?3) M NaCN (57 and 57% respectively). Kinetic analysis of the [(3)H]5HT high-affinity uptake in the hippocampus (3 min, 37 degrees C) revealed the same apparent K(m) for serotonin at both ages (6.7 x 10(?8) M), but a 44% decrease in V(max) in the aged hippocampal synaptosomal high-affinity uptake compared to adults (120 vs 215 pmol of 5-HT/g-tissue/3 min). These results are discussed in relationship to the reported age effects on the intrinsic neurons of the hippocampus.

Ascending endorphin inhibition of distress vocalization.

Distress vocalizations were produced in adult guinea pigs by electrical stimulation of the dorsomedial thalamus or the septum-preoptic area. Both of these forebrain-derived vocalizations were increased by systemic administration of naloxone and were inhibited by analgesic periventricular gray stimulation. Naloxone blocked the inhibitory effects of the analgesic stimulation on thalamic vocalizations. Stimulation of nonanalgesic mesencephalic sites in close proximity to the periventricular gray increased the anterior-elicited vocalizations. These data provide evidence for ascending endorphin-mediated inhibition of excitatory forebrain sites for distress vocalizations.

Immunocytochemical demonstration of met-enkephalin in the central nervous system of the domestic fowl.

In the central nervous system of the male domestic flow, metenkephalin (ENK) immunoreactive perikarya and fiber tracts as well as extensive but sharply delimited fiber networks were visualized by means of the PAP technique. The most striking results were: (1) The demonstration of an association of ENK-containing structures with branchial nerves; (2) the spatial relationship of ENK-containing perikarya and fibers to somatostatin (SOM) and arginine-vasotocin (AVT)-immunoreactive systems; (3) the presence of dense and extensive ENK fiber networks within (a) the caudo-basal wall of the third ventricle and (b) the septal-preoptic area; in both regions mainly ENK fibers, but also SOM and AVT fibers, may cross to the contralateral side.

Nuclear progestin receptors in guinea pig brain measured by an in vitro exchange assay after hormonal treatments that affect lordosis.

An assay was developed for the measurement of progestin receptors in purified cell nuclei of the central nervous system after progesterone injection. The affinity of the nuclear progestin receptor in the hypothalamus-preoptic area-septum of female guinea pigs for [3H]17α,21-dimethyl-19-nor-pregna-4,9- diene-3,20-dione (Kd ≧ 0.16 nm) is similar to that previously reported for the cytosol receptor in this tissue. Although all brain areas studied (hypothalamus, preoptic area-septum, midbrain, and cerebral cortex) accumulated some nuclear progestin receptor after progesterone injection, the hypothalamus had the highest concentration. Guinea pigs primed with a large dose (10 μg) of estradiol benzoate accumulated more nuclear progestin receptor after an injection of progesterone than animals primed with a low dose (1.6 μg) of estradiol benzoate. This is consistent with our previous finding that estradiol benzoate induces cytoplasmic progestin receptors in a dose-dependent manner. By 2–4 h after progesterone inj...

Modulation of Hypothalamic Luteinizing Hormone-Releasing Hormone Levels by Intracranial and Subcutaneous Implants of Gonadal Steroids in Castrated Rats: Effects of Androgen and Estrogen Antagonists*

Castration-induced hypersecretion of pituitary LH was associated with a marked reduction in the medial basal hypothalamic (MBH) LHRH contents. Testosterone (T) therapy promptly reduced LH to intact serum levels within 24 h, while the MBH LHRH levels were restored only after 7 days. Withdrawal of T replacement caused hypersecretion of LH within 8 h, although the first significant decrease in the MBH LHRH contents occurred between days 4–7. The two metabolites of T, 5α-dihydrotestosterone (DHT) and 17β-estradiol (E2), were as effective as T in raising the MBH LHRH content; however, their effects on serum LH were variable. The antiandrogen flutamide, but not the antiestrogen nafoxidine hydrochloride, blocked the stimulatory effects of T and DHT on MBH LHRH levels. Nafoxidine treatment was also ineffective in reversing this central effect of E2. None of these treatments significantly altered LHRH content in the preoptic area (POA). In view of the wide distribution of LHRH-containing neurons in the septal POA ...

Cytoplasmic progestin-receptors in guinea pig brain: Characteristics and relationship to the induction of sexual behavior

The synthetic progestin, R 5020, was used to measure cytoplasmic progestin receptors in the brain and pituitary gland of ovariectomized guinea pigs. Progestin receptors with a dissociation constant of 0.1–0.3 nM were measured by gel filtration in all brain regions studied, pituitary gland and the uterus. The receptor is progestin-specific; biologically potent progestins compete well against [ 3H]R 5020 for binding, but androgens, glucocoticoids and estrogens do not. The concentration of the cytoplasmic progestin receptor in hypothalamus-preoptic area-septum and midbrain is decreased in vivo by behaviorally effective doses of progesterone. In the pituitary gland, hypothalamus, preoptic area-septum and midbrain, but not other brain regions, the concentration of progestin receptors increases after estradiol benzoate-priming. The increase in the concentration of cytoplasmic progestin receptors in hypothalamus-preoptic area-septum is dependent on the dose of estradiol benzoate injected. After a single injection of a dose of estradiol benzoate routinely used to facilitate the display of sexual receptivity (1.6 μg estradiol benzoate/animal), the latency to an increase and subsequent decrease in cytoplasmic progestin receptors in the hypothalamus-preoptic area-septum correlates well with the previously reported time course for progesterone's facilitation of sexual receptivity after estradiol benzoate injection. The experiments are consistent with the notion that brain progestin receptors mediate at least some of the behavioral effects of progesterone.